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Theses & Dissertations: Cancer Research

Theses/dissertations from 2024 2024.

Novel Spirocyclic Dimer (SpiD3) Displays Potent Preclinical Effects in Hematological Malignancies , Alexandria Eiken

Chemotherapy-Induced Modulation of Tumor Antigen Presentation , Alaina C. Larson

Understanding the role of MASTL in colon homeostasis and colitis-associated cancer development , Kristina Pravoverov

Dying Right: Supporting Anti-Cancer Therapy Through Immunogenic Cell Death , Elizabeth Schmitz

Therapeutic Effects of BET Protein Inhibition in B-cell Malignancies and Beyond , Audrey L. Smith

Targeting KSR1 to inhibit stemness and therapy resistance , Heidi M. Vieira

Identifying the Molecular Determinants of Lung Metastatic Adaptation in Prostate Cancer , Grace M. Waldron

Identification of Mitotic Phosphatases and Cyclin K as Novel Molecular Targets in Pancreatic Cancer , Yi Xiao

Theses/Dissertations from 2023 2023

Development of Combination Therapy Strategies to Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors , Nicholas Mullen

Overcoming Resistance Mechanisms to CDK4/6 Inhibitor Treatment Using CDK6-Selective PROTAC , Sarah Truong

Theses/Dissertations from 2022 2022

Omics Analysis in Cancer and Development , Emalie J. Clement

Investigating the Role of Splenic Macrophages in Pancreatic Cancer , Daisy V. Gonzalez

Polymeric Chloroquine in Metastatic Pancreatic Cancer Therapy , Rubayat Islam Khan

Evaluating Targets and Therapeutics for the Treatment of Pancreatic Cancer , Shelby M. Knoche

Characterization of 1,1-Diarylethylene FOXM1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells , Cassie Liu

Novel Mechanisms of Protein Kinase C α Regulation and Function , Xinyue Li

SOX2 Dosage Governs Tumor Cell Identity and Proliferation , Ethan P. Metz

Post-Transcriptional Control of the Epithelial-to-Mesenchymal Transition (EMT) in Ras-Driven Colorectal Cancers , Chaitra Rao

Use of Machine Learning Algorithms and Highly Multiplexed Immunohistochemistry to Perform In-Depth Characterization of Primary Pancreatic Tumors and Metastatic Sites , Krysten Vance

Characterization of Metastatic Cutaneous Squamous Cell Carcinoma in the Immunosuppressed Patient , Megan E. Wackel

Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling , Pauline Xu

Phos-Tag-Based Screens Identify Novel Therapeutic Targets in Ovarian Cancer and Pancreatic Cancer , Renya Zeng

Theses/Dissertations from 2021 2021

Functional Characterization of Cancer-Associated DNA Polymerase ε Variants , Stephanie R. Barbari

Pancreatic Cancer: Novel Therapy, Research Tools, and Educational Outreach , Ayrianne J. Crawford

Apixaban to Prevent Thrombosis in Adult Patients Treated With Asparaginase , Krishna Gundabolu

Molecular Investigation into the Biologic and Prognostic Elements of Peripheral T-cell Lymphoma with Regulators of Tumor Microenvironment Signaling Explored in Model Systems , Tyler Herek

Utilizing Proteolysis-Targeting Chimeras to Target the Transcriptional Cyclin-Dependent Kinases 9 and 12 , Hannah King

Insights into Cutaneous Squamous Cell Carcinoma Pathogenesis and Metastasis Using a Bedside-to-Bench Approach , Marissa Lobl

Development of a MUC16-Targeted Near-Infrared Antibody Probe for Fluorescence-Guided Surgery of Pancreatic Cancer , Madeline T. Olson

FGFR4 glycosylation and processing in cholangiocarcinoma promote cancer signaling , Andrew J. Phillips

Theses/Dissertations from 2020 2020

Cooperativity of CCNE1 and FOXM1 in High-Grade Serous Ovarian Cancer , Lucy Elge

Characterizing the critical role of metabolic and redox homeostasis in colorectal cancer , Danielle Frodyma

Genomic and Transcriptomic Alterations in Metabolic Regulators and Implications for Anti-tumoral Immune Response , Ryan J. King

Dimers of Isatin Derived Spirocyclic NF-κB Inhibitor Exhibit Potent Anticancer Activity by Inducing UPR Mediated Apoptosis , Smit Kour

From Development to Therapy: A Panoramic Approach to Further Our Understanding of Cancer , Brittany Poelaert

The Cellular Origin and Molecular Drivers of Claudin-Low Mammary Cancer , Patrick D. Raedler

Mitochondrial Metabolism as a Therapeutic Target for Pancreatic Cancer , Simon Shin

Development of Fluorescent Hyaluronic Acid Nanoparticles for Intraoperative Tumor Detection , Nicholas E. Wojtynek

Theses/Dissertations from 2019 2019

The role of E3 ubiquitin ligase FBXO9 in normal and malignant hematopoiesis , R. Willow Hynes-Smith

BRCA1 & CTDP1 BRCT Domainomics in the DNA Damage Response , Kimiko L. Krieger

Targeted Inhibition of Histone Deacetyltransferases for Pancreatic Cancer Therapy , Richard Laschanzky

Human Leukocyte Antigen (HLA) Class I Molecule Components and Amyloid Precursor-Like Protein 2 (APLP2): Roles in Pancreatic Cancer Cell Migration , Bailee Sliker

Theses/Dissertations from 2018 2018

FOXM1 Expression and Contribution to Genomic Instability and Chemoresistance in High-Grade Serous Ovarian Cancer , Carter J. Barger

Overcoming TCF4-Driven BCR Signaling in Diffuse Large B-Cell Lymphoma , Keenan Hartert

Functional Role of Protein Kinase C Alpha in Endometrial Carcinogenesis , Alice Hsu

Functional Signature Ontology-Based Identification and Validation of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer , Beth Neilsen

Elucidating the Roles of Lunatic Fringe in Pancreatic Ductal Adenocarcinoma , Prathamesh Patil

Theses/Dissertations from 2017 2017

Metabolic Reprogramming of Pancreatic Ductal Adenocarcinoma Cells in Response to Chronic Low pH Stress , Jaime Abrego

Understanding the Relationship between TGF-Beta and IGF-1R Signaling in Colorectal Cancer , Katie L. Bailey

The Role of EHD2 in Triple-Negative Breast Cancer Tumorigenesis and Progression , Timothy A. Bielecki

Perturbing anti-apoptotic proteins to develop novel cancer therapies , Jacob Contreras

Role of Ezrin in Colorectal Cancer Cell Survival Regulation , Premila Leiphrakpam

Evaluation of Aminopyrazole Analogs as Cyclin-Dependent Kinase Inhibitors for Colorectal Cancer Therapy , Caroline Robb

Identifying the Role of Janus Kinase 1 in Mammary Gland Development and Breast Cancer , Barbara Swenson

DNMT3A Haploinsufficiency Provokes Hematologic Malignancy of B-Lymphoid, T-Lymphoid, and Myeloid Lineage in Mice , Garland Michael Upchurch

Theses/Dissertations from 2016 2016

EHD1 As a Positive Regulator of Macrophage Colony-Stimulating Factor-1 Receptor , Luke R. Cypher

Inflammation- and Cancer-Associated Neurolymphatic Remodeling and Cachexia in Pancreatic Ductal Adenocarcinoma , Darci M. Fink

Role of CBL-family Ubiquitin Ligases as Critical Negative Regulators of T Cell Activation and Functions , Benjamin Goetz

Exploration into the Functional Impact of MUC1 on the Formation and Regulation of Transcriptional Complexes Containing AP-1 and p53 , Ryan L. Hanson

DNA Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent of Error-Prone Synthesis, and the Role of dNTP Pools , Olga V. Kochenova

Defining the Role of Phosphorylation and Dephosphorylation in the Regulation of Gap Junction Proteins , Hanjun Li

Molecular Mechanisms Regulating MYC and PGC1β Expression in Colon Cancer , Jamie L. McCall

Pancreatic Cancer Invasion of the Lymphatic Vasculature and Contributions of the Tumor Microenvironment: Roles for E-selectin and CXCR4 , Maria M. Steele

Altered Levels of SOX2, and Its Associated Protein Musashi2, Disrupt Critical Cell Functions in Cancer and Embryonic Stem Cells , Erin L. Wuebben

Theses/Dissertations from 2015 2015

Characterization and target identification of non-toxic IKKβ inhibitors for anticancer therapy , Elizabeth Blowers

Effectors of Ras and KSR1 dependent colon tumorigenesis , Binita Das

Characterization of cancer-associated DNA polymerase delta variants , Tony M. Mertz

A Role for EHD Family Endocytic Regulators in Endothelial Biology , Alexandra E. J. Moffitt

Biochemical pathways regulating mammary epithelial cell homeostasis and differentiation , Chandrani Mukhopadhyay

EPACs: epigenetic regulators that affect cell survival in cancer. , Catherine Murari

Role of the C-terminus of the Catalytic Subunit of Translesion Synthesis Polymerase ζ (Zeta) in UV-induced Mutagensis , Hollie M. Siebler

LGR5 Activates TGFbeta Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

LGR5 Activates TGFβ Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

Theses/Dissertations from 2014 2014

Genetic dissection of the role of CBL-family ubiquitin ligases and their associated adapters in epidermal growth factor receptor endocytosis , Gulzar Ahmad

Strategies for the identification of chemical probes to study signaling pathways , Jamie Leigh Arnst

Defining the mechanism of signaling through the C-terminus of MUC1 , Roger B. Brown

Targeting telomerase in human pancreatic cancer cells , Katrina Burchett

The identification of KSR1-like molecules in ras-addicted colorectal cancer cells , Drew Gehring

Mechanisms of regulation of AID APOBEC deaminases activity and protection of the genome from promiscuous deamination , Artem Georgievich Lada

Characterization of the DNA-biding properties of human telomeric proteins , Amanda Lakamp-Hawley

Studies on MUC1, p120-catenin, Kaiso: coordinate role of mucins, cell adhesion molecules and cell cycle players in pancreatic cancer , Xiang Liu

Epac interaction with the TGFbeta PKA pathway to regulate cell survival in colon cancer , Meghan Lynn Mendick

Theses/Dissertations from 2013 2013

Deconvolution of the phosphorylation patterns of replication protein A by the DNA damage response to breaks , Kerry D. Brader

Modeling malignant breast cancer occurrence and survival in black and white women , Michael Gleason

The role of dna methyltransferases in myc-induced lymphomagenesis , Ryan A. Hlady

Design and development of inhibitors of CBL (TKB)-protein interactions , Eric A. Kumar

Pancreatic cancer-associated miRNAs : expression, regulation and function , Ashley M. Mohr

Mechanistic studies of mitochondrial outer membrane permeabilization (MOMP) , Xiaming Pang

Novel roles for JAK2/STAT5 signaling in mammary gland development, cancer, and immune dysregulation , Jeffrey Wayne Schmidt

Optimization of therapeutics against lethal pancreatic cancer , Joshua J. Souchek

Theses/Dissertations from 2012 2012

Immune-based novel diagnostic mechanisms for pancreatic cancer , Michael J. Baine

Sox2 associated proteins are essential for cell fate , Jesse Lee Cox

KSR2 regulates cellular proliferation, transformation, and metabolism , Mario R. Fernandez

Discovery of a novel signaling cross-talk between TPX2 and the aurora kinases during mitosis , Jyoti Iyer

Regulation of metabolism by KSR proteins , Paula Jean Klutho

The role of ERK 1/2 signaling in the dna damage-induced G2 , Ryan Kolb

Regulation of the Bcl-2 family network during apoptosis induced by different stimuli , Hernando Lopez

Studies on the role of cullin3 in mitosis , Saili Moghe

Characteristics of amyloid precursor-like protein 2 (APLP2) in pancreatic cancer and Ewing's sarcoma , Haley Louise Capek Peters

Structural and biophysical analysis of a human inosine triphosphate pyrophosphatase polymorphism , Peter David Simone

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Exploring and optimizing therapeutic strategies for borderline ovarian tumors and low-grade serous ovarian cancer

Area: Public Health

The thesis of Koen de Decker was aimed at exploring and optimizing therapeutic strategies for borderline ovarian tumors and low-grade serous ovarian cancer. Based on our study and a thorough review of the existing literature, it can be concluded that mucinous borderline ovarian tumors very rarely present with extraovarian disease. Surgical staging procedures, with the aim of detecting extraovarian disease, can be omitted safely without compromising progression-free and overall survival rates. Omission of a staging procedure implicates less comprehensive surgery and decreased surgical morbidity, which is beneficial to the patient.

Provisional diagnoses of borderline ovarian tumors are often made intraoperatively using the frozen section technique. However, it is not always possible to report a frozen section diagnosis as a borderline ovarian tumor or an invasive carcinoma and we showed that one fourth of borderline ovarian tumor diagnoses are classified as “at least borderline” upon frozen section evaluation. Nearly half of these patients had ovarian cancer as a final diagnosis. Because surgical management is based upon the frozen section result, and is different for borderline tumors and ovarian cancer, this is a dilemma for both the surgeon and pathologist.

The main findings with respect to low-grade serous carcinoma in The Netherlands (2000–2019) were increased annual incidence rates, increased numbers of patients with advanced stage disease, prognostic significance of the extent to which the disease could be removed during surgery, and overall relative survival rates that did not significantly change over time. Furthermore, an increasing percentage of patients started treatment with neoadjuvant chemotherapy, which is associated with worse survival compared to starting treatment with a surgical procedure.

NWO Demonstrator grant for De Boer’s counter-intuitive treatment for cholestatic liver disease

Renal function in critically ill patients: assessment, replacement and histopathology

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Advances in Ovarian Cancer Research: From Biology to Therapeutics

Dear Colleagues,

Recently, substantial progress has been made in treating ovarian cancer, predominantly based on the identification of new molecular targets. For example, PARP inhibitors have been successful largely due to their efficacy in cancers that harbor BRCA mutations or evidence of deficiency in the homologous recombination DNA repair pathway. This collection of articles will address the biological discoveries leading to the next breakthroughs in ovarian cancer research and treatment. Authors are encouraged to submit research studies with translational potential, especially those that include novel biomarkers for treatment effects. This topic thus provides a framework for integrating discoveries at the bench and the bedside.

Dr. Christina M. Annunziata Prof. Dr. Adam R. Karpf Topic Editors

ovarian cancer
translational research
epigenetics
clinical trials
tumor biology
drug discovery

Journal Name	Launched Year	First Decision (median)	APC
biomolecules	2011	16.3 Days	CHF 2700
cancers	2009	16.3 Days	CHF 2900
cells	2012	17.5 Days	CHF 2700
curroncol	1994	17.6 Days	CHF 2200

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Ovarian cancer articles from across Nature Portfolio

Ovarian cancer is an abnormal cell growth (tumour) arising in the ovary. The majority of ovarian cancers are epithelial and develop in women over 50. Screening is highly recommended in women with a family history of ovarian cancer.

Latest Research and Reviews

SGK1 suppresses ferroptosis in ovarian cancer via NRF2-dependent and -independent pathways

Xiaolin Sang

Validation of the BOADICEA model for epithelial tubo-ovarian cancer risk prediction in UK Biobank

Antonis C. Antoniou

Y-box binding protein 1/cyclin A1 axis specifically promotes cell cycle progression at G 2 /M phase in ovarian cancer

Yuichi Murakami
Daisuke Katsuchi
Michihiko Kuwano

Human papillomavirus infection of the fallopian tube as a potential risk factor for epithelial ovarian cancer

Edyta Paradowska
Daria A. Haręża
Jacek R. Wilczyński

Predicting prognosis for epithelial ovarian cancer patients receiving bevacizumab treatment with CT-based deep learning

Xiaoyu Huang

Fractionated photoimmunotherapy stimulates an anti-tumour immune response: an integrated mathematical and in vitro study

Mohammad U. Zahid
Matthew Waguespack
Heiko Enderling

News and Comment

Mirvetuximab soravtansine has activity in platinum-sensitive epithelial ovarian cancer.

Diana Romero

Mirvetuximab soravtansine superior to chemotherapy in platinum-resistant epithelial ovarian cancer

Peter Sidaway

A medley of resistance in ovarian cancers

Multi-omic profiling of lesions at autopsy reveals a plethora of resistance mechanisms present within individual patients with ovarian cancer. This highlights the extreme challenge faced in treating end-stage disease and underscores the need for new methods of early detection and intervention.

Barbara Hernando
Geoff Macintyre

A biomarker-driven therapy for ovarian cancer

An antibody–drug conjugate showed impressive anti-cancer activity in selected patients with platinum-resistant ovarian cancer, and could become a new standard of care.

Karen O’Leary

Beating the odds: molecular characteristics of long-term survivors of ovarian cancer

High-grade serous ovarian cancer, the most common form of the disease, is often fatal. This study investigated the genomic and immune characteristics of tumors from women who survived more than 10 years after their initial diagnosis, and compared them with short-term and moderate-term survivors.

Cytoreductive surgery effective after relapse

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Ovarian Cancer: An Integrated Review

Affiliations.

1 Carolina's Medical Center, Charlotte, NC. Electronic address: [email protected].
2 Assistant Vice President Patient Care Services, Carolina's Medical Center, Rock Hill, SC.
3 Interim Dean, Harris College of Nursing & Health Sciences, Associate Dean for Nursing & Professor, Texas Christian University, Ft Worth, TX.
PMID: 30867104
DOI: 10.1016/j.soncn.2019.02.001

Objective: To provide an overview of the risk factors, modifiable and non-modifiable, for ovarian cancer as well as prevention, diagnostic, treatment, and long-term survivorship concerns. This article will also examine current and future clinical trials surrounding ovarian cancer.

Data sources: A review of articles dated 2006-2018 from CINAHL, UpToDate, and National Comprehensive Cancer Network guidelines.

Conclusion: There is no screening test for ovarian cancer and with diagnosis often in the late stages, recurrence is high in this population. Early identification can range from knowing the vague symptoms associated with the cancer to prophylactic surgical removal of at-risk tissue. Standard treatment for ovarian cancer is surgery followed by combination chemotherapy. Although advances are being made, ovarian cancer remains the most fatal female gynecologic cancer.

Implications for nursing practice: Becoming familiar with and educating women about risk factors and the elusive symptoms of ovarian cancer can increase patient autonomy and advocacy, as well as potentially improve patient outcomes for those affected by ovarian cancer.

Keywords: BRCA; gynecologic; oncology; ovarian cancer; prevention; risk factors.

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Advances in Ovarian Cancer Research

Image from a mouse model of ovarian cancer in color-enhanced 3D detail.

An ovarian tumor grown in a mouse using human cells. Special techniques were used to create the high-resolution, 3-D view of the cancer’s cell structure and inner workings.

The most common ovarian cancers are those that begin in the epithelial cells that line the fallopian tubes or ovaries . These, along with cancers that form in the peritoneum , are called epithelial ovarian cancers . Other types of ovarian cancer arise in other cells, including germ cell tumors , which start in the cells that make eggs, and stromal cell tumors , which start in supporting tissues.

NCI-funded researchers are working to advance our understanding of how to prevent, detect early, and treat ovarian cancer.

This page highlights some of what’s new in the latest research in ovarian cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Prevention of Ovarian Cancer

Women who carry harmful or potentially harmful mutations in the BRCA1 or BRCA2 genes are at increased risk of developing ovarian cancer. Surgery to remove the ovaries and fallopian tubes in these women is the recommended treatment method and can reduce their lifetime risk of getting ovarian cancer by 95%. However, having this surgery causes immediate menopause. This may cause health problems if it is much earlier than naturally occurring menopause.

Research has shown that the most common type of ovarian cancer begins in the fallopian tubes , not in the ovaries. This discovery has led doctors to reconsider ways of preventing ovarian cancer.

Removing fallopian tubes only. An ongoing NCI-sponsored clinical trial is testing whether removing the fallopian tubes but delaying removal of the ovaries will be as safe and effective to reduce the risk of ovarian cancer in women with BRCA1 mutations as removing both the ovaries and fallopian tubes at the same time. This would allow women to maintain premenopausal levels of hormones produced by the ovaries and delay many of the complications associated with menopause.
Removal of fallopian tubes in people seeking to prevent pregnancy. The discovery that epithelial ovarian cancers most often start in the fallopian tubes has also led to changes in the way some gynecologists approach surgery to prevent pregnancy. Women seeking tubal ligation to prevent pregnancy (often called having your tubes tied) may be offered the option of having their tubes removed instead. Doing so might reduce the possibility of ovarian cancer in the future.
Removal of fallopian tubes in people undergoing a hysterectomy. Similarly, some gynecologists recommend that their patients who are undergoing a hysterectomy also have their fallopian tubes removed.
Testing relatives for gene mutations. NCI is funding efforts to test the relatives of women who have been diagnosed with ovarian cancer in the past. Researchers are locating women diagnosed with ovarian cancer with the hope to test them and/or their family members for ovarian cancer-related gene mutations. As a result, family members who learn they carry a mutation can take steps to reduce their risk. The overall goal is not only to prevent ovarian cancer, but also to find the best ways to communicate sensitive genetic information to ovarian cancer patients and their family members.

Ovarian Cancer Treatment

Surgery and chemotherapy are the main treatments for ovarian cancer. The location and type of cells where the cancer begins, and whether the cancer is high-grade or low-grade , influences how the cancer is treated. Surgery can cure most people with early-stage ovarian cancer that has not spread beyond the ovaries. For advanced ovarian cancer, the goal of surgery is to remove as much of the cancer as possible, called surgical debulking .

Platinum-based chemotherapy drugs, such as cisplatin or carboplatin , given in combination with other drugs, such as the targeted therapy bevacizumab (Avastin) , are usually effective in treating epithelial ovarian cancer at any stage. However, in most people with advanced ovarian cancer, the cancer comes back. Treating the cancer again with platinum drugs may work, but eventually the tumors become resistant to these drugs.

Targeted Therapy

Targeted therapy uses drugs or other agents to attack specific types of cancer cells. PARP inhibitors are a type of targeted therapy that can stop a cancer cell from repairing its damaged DNA , causing the cell to die. Cancers in people who have certain mutations in the BRCA genes are considered particularly susceptible to PARP inhibitors. That’s because BRCA genes are involved in the repair of some types of DNA damage, so cancers with alterations in these genes already have defects in DNA repair.

The use of PARP inhibitors has transformed treatment for people with advanced epithelial ovarian cancer who have harmful mutations in a BRCA gene. Since the 2014 approval of olaparib (Lynparza) , the first PARP inhibitor to be approved, the number of PARP inhibitors has grown and their uses for people with ovarian cancer have expanded. Now researchers are studying the benefits of combining PARP inhibitors with other drugs.

Clinical trials have shown that using PARP inhibitors as long-term therapy in women with advanced epithelial ovarian cancer delayed progression of the cancer.

A different targeted therapy, mirvetuximab soravtansine (Elahere) , is now available to treat women with ovarian cancer that is no longer responding to platinum drugs. FDA recently approved the drug to treat people with platinum-resistant ovarian tumors that produce an excess of a protein called FR-α. Results from a large clinical trial showed that people with this type of ovarian cancer treated with mirvetuximab lived longer overall than people treated with standard chemotherapy .

Treatment after Cancer Progression

Typically, chemotherapy and targeted therapies are stopped once ovarian cancer begins to come back. Clinical trials have shown that where there was more than a 6 month delay between stopping treatment and cancer being found again, resuming the drug bevacizumab (Avastin) in combination with platinum-based chemotherapy for patients previously treated with bevacizumab slowed the growth of platinum-sensitive disease . And in women who no longer benefited from platinum-based chemotherapy, non–platinum-based chemotherapy combined with bevacizumab kept the cancer in check longer than chemotherapy alone.

Targeted therapies may also be helpful for people with low-grade ovarian cancer. A trial of the drug trametinib in women with low-grade serous ovarian cancer that had come back showed that it delayed the cancer’s growth compared with treating the cancer with chemotherapy again.

Secondary Surgery

For women with advanced epithelial ovarian cancer that has come back after being in remission, clinical trials have studied the use of secondary surgery or surgery to remove more tumor after the initial surgery with varying results.

An NCI-funded phase 3 clinical trial, in patients whose doctor felt that a second surgery could be helpful for treating the cancer, found that secondary surgery followed by chemotherapy did not increase overall survival compared with chemotherapy alone. Of the studies listed, this one reflected the most likely scenario in real-world practice.
A trial done in China studied a group of patients more likely to benefit from the intervention. The trial tested secondary surgery followed by chemotherapy and did show improvements in how long women with recurrent epithelial ovarian cancer lived without their cancer growing .
In a third trial, conducted in Europe, researchers identified people with recurrent ovarian cancer who were most likely to benefit from surgery. They found that women who had secondary surgery followed by chemotherapy lived an average of nearly 8 months longer than women who only received chemotherapy.

In the Chinese and European trials, and in an analysis of 64 clinical trials and other studies , the benefits of secondary surgery were observed only in women who had all of their visible cancer removed.

NCI-Supported Research Programs

Many NCI-funded researchers at the National Institutes of Health campus, and across the United States and the world, are seeking ways to address ovarian cancer more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of ovarian cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate this basic information into improving patient outcomes.

The Women’s Malignancies Branch in NCI’s Center for Cancer Research conducts basic and clinical research in breast and gynecologic cancers, including early-phase clinical trials at the NIH Clinical Center in Bethesda, Maryland.

The Ovarian Specialized Programs of Research Excellence (SPOREs) promote collaborative translational cancer research. This group works to improve prevention and treatment approaches, along with molecular diagnostics , in the clinical setting to help people with ovarian cancer.

The Ovarian Cancer Cohort Consortium , part of the NCI Cohort Consortium, is an international consortium of more than 20 cohort studies that follow people with ovarian cancer to improve understanding of ovarian cancer risk, early detection, tumor differences, and prognosis.

NCI’s clinical trials programs, the National Clinical Trials Network , Experimental Therapeutics Clinical Trials Network , and NCI Community Oncology Research Program , all conduct or sponsor clinical studies of ovarian cancer.

Clinical Trials for Ovarian Cancer

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for the treatment of ovarian cancer.

Ovarian Cancer Research Results

The following are some of our latest news articles on ovarian cancer research:

Approval of Elahere Expands Treatment Options for Some Advanced Ovarian Cancers

Implanted “Drug Factories” Deliver Cancer Treatment Directly to Tumors

Trametinib Is a New Treatment Option for Rare Form of Ovarian Cancer

When Ovarian Cancer Returns, Surgery May Be a Good Choice for Selected Patients

How Does Ovarian Cancer Form? A New Study Points to MicroRNA

Ovarian Cancer Studies Aim to Reduce Racial Disparities, Improve Outcomes

View the full list of Ovarian Cancer Research Results and Study Updates .

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Mechanism study of YangJing ZhongYu decoction on regulating mitochondrial dynamics of ovarian granular cells and improving diminished ovarian reserve

Diminished ovarian reserve (DOR) encompasses both reproductive and endocrine disorders, resulting in a decline in female fertility. This paper explored the mechanism of Yangjing Zhongyu Decoction (YJZYD) regul...

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The synergistic mechanisms of propofol with cisplatin or doxorubicin in human ovarian cancer cells

Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence f...

The discriminatory capability of anthropometric measures in predicting reproductive outcomes in Chinese women with PCOS

Obesity is a common feature in women with polycystic ovary syndrome (PCOS) and potentially significantly influences reproductive function. However, opinions are divided as to which factor is a more appropriate...

Long non-coding ribonucleic acid SNHG18 induced human granulosa cell apoptosis via disruption of glycolysis in ovarian aging

In-depth understanding of dynamic expression profiles of human granulosa cells (GCs) during follicular development will contribute to the diagnostic and targeted interventions for female infertility. However, ...

Bone marrow mesenchymal stem cells expressing Neat-1, Hotair-1, miR-21, miR-644, and miR-144 subsided cyclophosphamide-induced ovarian insufficiency by remodeling the IGF-1–kisspeptin system, ovarian apoptosis, and angiogenesis

Ovarian insufficiency is one of the common reproductive disorders affecting women with limited therapeutic aids. Mesenchymal stem cells have been investigated in such disorders before yet, the exact mechanism ...

Research progress of ferroptosis in female infertility

Ferroptosis is a novel type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides in cells and is closely related to various diseases. Female infertility is a glob...

Stem cell-derived extracellular vesicles in premature ovarian failure: an up-to-date meta-analysis of animal studies

There has been a significant surge in animal studies of stem cell-derived extracellular vesicles (EVs) therapy for the treatment of premature ovarian failure (POF) but its efficacy remains unknown and a compre...

Evaluation of the cytotoxic activity of chemically characterized propolis originating from different geographic regions and vitamin D co-supplementation against human ovarian cancer cells

Ovarian cancer is the second most common and lethal gynecologic malignancy. Among natural product-based therapy, the honeybee products, particularly propolis, serve a valuable source contributing directly to h...

A novel heterozygous missense variant of PANX1 causes human oocyte death and female infertility

Pannexin1 (PANX1) is a highly glycosylated membrane channel-forming protein, which has been found to implicate in multiple physiological and pathophysiological functions. Variants in the PANX1 gene have been repo...

Increasing dominant follicular proportion was associated with adverse IVF/ICSI outcomes in low-prognosis women undergoing GnRH antagonist protocol: a retrospective cohort study

This study aimed to examine the correlation between different dominant follicle proportions (DFPs) and outcomes of in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) among patients classifie...

SCM-198 ameliorates the quality of postovulatory and maternally aged oocytes by reducing oxidative stress

Oocyte aging is a key constraint on oocyte quality, leading to fertilization failure and abnormal embryonic development. In addition, it is likely to generate unfavorable assisted reproductive technology (ART)...

Efficacy and safety of Shen Que (RN8) moxibustion on reproductive outcomes in unexpected poor ovarian responders: a randomized controlled trial

Managing infertility patients with poor ovarian response (POR) to ovarian stimulation remains unmet clinically. Besides economic burdens, patients with POR have a poor prognosis during in vitro fertilization a...

B4GALT5 a sialylation-related genes associated with patient prognosis and immune microenvironment in ovarian cancer and pan-cancer

Ovarian cancer (OC) is the predominant primary tumor in the human reproductive system. Abnormal sialylation has a significant impact on tumor development, metastasis, immune evasion, angiogenesis, and treatmen...

Sterigmatocystin declines mouse oocyte quality by inducing ferroptosis and asymmetric division defects

Sterigmatocystin (STE) is a mycotoxin widely found in contaminated food and foodstuffs, and excessive long-term exposure to STE is associated with several health issues, including infertility. However, there i...

Association of HOMA-IR with unexpected poor ovarian response in non-obese women in poseidon 1: a retrospective cohort study

Insulin resistance (IR) is related with adverse outcomes of in vitro fertilization (IVF) in women with obesity, but little is known about the relationship between IR and unexpected poor ovarian response (uPOR)...

The diagnostic performance of CA-125 for the detection of ovarian cancer in women from different ethnic groups: a cohort study of English primary care data

CA-125 testing is a recommended first line investigation for women presenting with possible symptoms of ovarian cancer in English primary care, to help determine whether further investigation for ovarian cance...

Ovarian cancer derived extracellular vesicles promote the cancer progression and angiogenesis by mediating M2 macrophages polarization

Extracellular vesicles (EVs) are mediators between cancer cells and other types of cells, such as tumor-associated macrophages (TAMs), in the tumor microenvironment. EVs can remodel the tumor microenvironment ...

Stem cell-based therapeutic potential in female ovarian aging and infertility

Premature ovarian insufficiency (POI) is defined as onset of menopause characterized by amenorrhea, hypergonadotropism, and hypoestrogenism, before the age of 40 years. The POI is increasing, which seriously a...

Prognostic analysis of peritoneal washing cytology during interval debulking surgery in advanced ovarian cancer

Interval debulking surgery (IDS) following neoadjuvant chemotherapy is a treatment option for advanced ovarian cancer. Optimal surgery is required for better survival; however, while peritoneal washing cytolog...

Preovulatory progesterone levels are the top indicator for ovulation prediction based on machine learning model evaluation: a retrospective study

Accurately predicting ovulation timing is critical for women undergoing natural cycle-frozen embryo transfer. However, the precise predicting of the ovulation timing remains challenging due to the lack of cons...

Correction: Amniotic fluid-derived exosomes attenuated fibrotic changes in POI rats through modulation of the TGF-β/Smads signaling pathway

The original article was published in Journal of Ovarian Research 2023 16 :118

Granulosa cell insight: unraveling the potential of menstrual blood-derived stem cells and their exosomes on mitochondrial mechanisms in polycystic ovary syndrome (PCOS)

Polycystic ovary syndrome (PCOS) presents a significant challenge in women’s reproductive health, characterized by disrupted folliculogenesis and ovulatory dysfunction. Central to PCOS pathogenesis are granulo...

A metabolome-wide Mendelian randomization study prioritizes causal circulating metabolites for reproductive disorders including primary ovarian insufficiency, polycystic ovary syndrome, and abnormal spermatozoa

Accumulating studies have highlighted the significant role of circulating metabolomics in the etiology of reproductive system disorders. However, the causal effects between genetically determined metabolites (...

Evaluation of ovarian reserve and the assisted reproductive technology (ART) cycles’ outcome as well as the relapse rate within one year after ART in women with multiple sclerosis: a case-control study

To compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with mul...

CA-125:CA72-4 ratio − towards a promising cost-effective tool in ovarian cancer diagnosis and monitoring of post-menopausal women under hormone treatment

Ovarian cancer (OC) is the most lethal gynecological cancer in the developed world. Most cases are diagnosed at late stage III-IV with a very low 5-year overall survival rate. Several studies revealed an eleva...

Effect of astaxanthin supplementation on female fertility and reproductive outcomes: a systematic review and meta-analysis of clinical and animal studies

Oxidative stress (OS) plays a harmful role in female reproduction and fertility. Several studies explored various dietary interventions and antioxidant supplements, such as astaxanthin (AST), to mitigate the a...

Dachsous cadherin related 1 (DCHS1) is a novel biomarker for immune infiltration and epithelial-mesenchymal transition in endometrial cancer via pan-cancer analysis

Dachsous cadherin related 1 (DCHS1) is one of calcium-dependent adhesion membrane proteins and is mainly involved in the development of mammalian tissues. There is a lack of more detailed research on the biolo...

Emerging role of mucins in antibody drug conjugates for ovarian cancer therapy

Ovarian cancer stands as the deadliest gynecologic malignancy, responsible for nearly 65% of all gynecologic cancer-related deaths. The challenges in early detection and diagnosis, coupled with the widespread ...

Extracellular vesicles and their content in the context of polycystic ovarian syndrome and endometriosis: a review

Extracellular vesicles (EVs), particles enriched in bioactive molecules like proteins, nucleic acids, and lipids, are crucial mediators of intercellular communication and play key roles in various physiologica...

The molecular prognostic score, a classifier for risk stratification of high-grade serous ovarian cancer

The clinicopathological parameters such as residual tumor, grade, the International Federation of Gynecology and Obstetrics (FIGO) score are often used to predict the survival of ovarian cancer patients, but t...

Drug-free in vitro activation combined with ADSCs-derived exosomes restores ovarian function of rats with premature ovarian insufficiency

Drug-free in vitro activation (IVA) is a new protocol to activate residual dormant follicles for fertility restoration in patients with premature ovarian insufficiency (POI). However, several deficiencies have...

Effects of licorice extract in combination with a low-calorie diet on obesity indices, glycemic indices, and lipid profiles in overweight/obese women with polycystic ovary syndrome (PCOS): a randomized, double-blind, placebo-controlled trial

Polycystic ovary syndrome (PCOS) is the most common ovarian dysfunction. Recent studies showed the effectiveness of licorice on metabolic profiles with inconsistent findings. So, we investigated the effect of ...

Unveiling G-protein coupled receptors as potential targets for ovarian cancer nanomedicines: from RNA sequencing data analysis to in vitro validation

Genetic heterogeneity in ovarian cancer indicates the need for personalised treatment approaches. Currently, very few G-protein coupled receptors (GPCRs) have been investigated for active targeting with nanome...

Correction: Metformin modifies plasma microbial-derived extracellular vesicles in polycystic ovary syndrome with insulin resistance

The original article was published in Journal of Ovarian Research 2024 17 :136

Effects of mind-body interventions on polycystic ovary syndrome: a comprehensive meta-analysis

Mind-body interventions (MBI) have emerged as a potential therapeutic approach, but their effectiveness in the treatment of Polycystic Ovary Syndrome (PCOS) remains inconclusive. This study systematically eval...

The natural menstrual cycle revisited – can natural cycle be trusted

The serum progesterone (P4) level during the luteal phase (LP) plays a crucial role in the initiation and maintenance of pregnancy. However, it is unclear whether the natural cycle consistently provides the be...

External validation of Standardized KELIM and platinum-resistant recurrence scores in patients with advanced epithelial ovarian cancer

Neoadjuvant chemotherapy followed by interval debulking surgery is currently a common treatment option for advanced epithelial ovarian cancer (EOC). The Standardized CA-125 ELIMination rate constant K (Std KEL...

Hsa_circ_0043532 contributes to PCOS through upregulation of CYP19A1 by acting as a ceRNA for hsa-miR-1270

Polycystic ovarian syndrome (PCOS) accounts for about 75% of anovulatory infertility. The cause of PCOS is not clear. CircRNAs acting as miRNA sponges mediate the post-transcriptional regulation of multiple ge...

Acetylation model predicts prognosis of patients and affects immune microenvironment infiltration in epithelial ovarian carcinoma

Epithelial ovarian carcinoma (EOC) is a prevalent gynaecological malignancy. The prognosis of patients with EOC is related to acetylation modifications and immune responses in the tumour microenvironment (TME)...

Targeted proteomics of plasma extracellular vesicles uncovers MUC1 as combinatorial biomarker for the early detection of high-grade serous ovarian cancer

The five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential ...

The role of vitamin D3 in follicle development

Vitamin D3 plays a crucial role in female reproduction. As research progresses, the mechanisms of action of vitamin D3 on follicular development have been widely discussed. Firstly, key enzymes involved in the...

Effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome: a randomized controlled trial

The aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome (PCOS).

Causal association between telomere length and female reproductive endocrine diseases: a univariable and multivariable Mendelian randomization analysis

The relationship between leukocyte telomere length (LTL) and female reproductive endocrine diseases has gained significant attention and research interest in recent years. However, there is still limited under...

The impact of Paclitaxel-based hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer patients - interim analysis of safety and immediate efficacy of a randomized control trial (C-HOC trial)

This study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant ...

The possible short-term of Nigella sativa – L in the management of adolescent polycystic ovarian syndrome: results of a randomized controlled trial

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age and the most common cause of infertility due to anovulation. PCOS in adolescents is concerning. Nigella sativa is effe...

Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial

This study was designed to examine the effect of resveratrol on mitochondrial biogenesis, oxidative stress (OS), and assisted reproductive technology (ART) outcomes in individuals with polycystic ovary syndrom...

Comprehensive analysis of hub genes associated with cisplatin-resistance in ovarian cancer and screening of therapeutic drugs through bioinformatics and experimental validation

To identify key genes associated with cisplatin resistance in ovarian cancer, a comprehensive analysis was conducted on three datasets from the GEO database and through experimental validation.

Depletion of placental brain-derived neurotrophic factor (BDNF) is attributed to premature ovarian insufficiency (POI) in mice offspring

Premature ovarian insufficiency (POI) is one of the causes of female infertility. Unexplained POI is increasingly affecting women in their reproductive years. However, the etiology of POI is diverse and remain...

The intratumoral microbiota biomarkers for predicting survival and efficacy of immunotherapy in patients with ovarian serous cystadenocarcinoma

Ovarian serous cystadenocarcinoma, accounting for about 90% of ovarian cancers, is frequently diagnosed at advanced stages, leading to suboptimal treatment outcomes. Given the malignant nature of the disease, ...

Ovarian fibrosis: molecular mechanisms and potential therapeutic targets

Ovarian fibrosis, characterized by the excessive proliferation of ovarian fibroblasts and the accumulation of extracellular matrix (ECM), serves as one of the primary causes of ovarian dysfunction. Despite the...

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A new FDA approved phase I/II clinical trial on recurrent ovarian cancer is now open for enrollment.

Currently recruiting patients at the Brown Cancer Center, University of Louisville, Louisville, KY. UofL. IRB# 22.0392. NCT# 05610735. Please contact: Dr. Whitney Goldsberry or Dr. Sham S. Kakar .

Journal of Ovarian Research

ISSN: 1757-2215

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Ovarian cancer: New treatments and research

New targeted therapies are improving survival.

Surgery and chemotherapy are no longer the only options for ovarian cancer treatment . Targeted therapies use drugs to target and attack cancer cells. These include monoclonal antibodies and poly (ADP-ribose) polymerase, or PARP, inhibitors.

Monoclonal antibodies

Monoclonal antibodies are molecules engineered in the laboratory to find and attach to specific proteins associated with cancer cells. Bevacizumab is a monoclonal antibody used with chemotherapy to treat ovarian cancer recurrence by preventing the growth of new blood vessels that tumors need to grow.

Researchers are combining bevacizumab with new drugs to improve outcomes. One example is a monoclonal antibody recently approved by the Food and Drug Administration (FDA) called mirvetuximab soravtansine for people with ovarian cancer recurrence. This drug is used when a person's cancer was previously treated with at least one systemic therapy to target a protein called folate receptor alpha.

"Ovarian cancers have many folate receptors. Most normal cells don't," says Dr. Weroha. "This drug is an antibody that has chemotherapy stuck onto it. Think of it as a guided missile traveling the body and sticking to cells with folate receptors. In patients whose ovarian cancer has recurred and whose tumors have many folate receptors, mirvetuximab soravtansine can shrink tumors far better than any other therapy. The response rate is about double what you see with any other treatment."

PARP inhibitors

PARP inhibitors are drugs that block DNA repair, which may cause cancer cells to die. Olaparib is an example of a PARP inhibitor used to prevent recurrence in people with ovarian cancer whose tumors have BRCA1 or BRCA2 gene mutations. Research has shown that olaparib can significantly improve survival without recurrence in people with this diagnosis. "This is a front-line treatment, which means this is part of the first treatment regimen patients receive when they are newly diagnosed," says Dr. Weroha.

A vaccine may one day be used to fight ovarian cancer.

Matthew Block, M.D., Ph.D. , a Mayo Clinic medical oncologist, and Keith Knutson, Ph.D. , a Mayo Clinic researcher, are developing a vaccine to prevent ovarian cancer tumors from returning in people with advanced ovarian cancer whose tumors have recurred after surgery and chemotherapy.

White blood cells are extracted from a blood draw and manufactured to become dendritic cells — immune cells that boost immune responses. These cells are returned to the patient in vaccine form to trigger the immune system to recognize and fight the cancer.

The vaccine will be given in combination with an immunotherapy drug called pembrolizumab to identify and kill any tumors that don't respond to the dendritic cells.

"Pembrolizumab is in a category of drugs called immune checkpoint inhibitors ," says Dr. Weroha. "This drug is designed to release the brakes on the immune system to allow it to do what it naturally wants: kill things it doesn't like. The hope is that the vaccine combined with the immunotherapy drug will kill a lot of ovarian cancer. It's exciting research."

A screening test may be on the horizon.

There is no screening test for ovarian cancer, but Jamie Bakkum-Gamez, M.D. , a Mayo Clinic gynecologic oncologist, is hoping to change that. She and her research team discovered that methylated DNA markers could be used to identify endometrial cancer through vaginal fluid collected with a tampon. Eventually, this same science could extend to ovarian cancer.

Methylation is a mechanism cells use to control gene expression — the process by which a gene is switched on in a cell to make RNA and proteins. When a certain area of a gene's DNA is methylated, the gene is turned off or silenced, indicating that a gene is a tumor suppressor. The silencing of tumor suppressor genes is often an early step in cancer development and can suggest cancer.

Dr. Bakkum-Gamez and her colleagues developed a panel of methylated DNA markers that could distinguish between endometrial cancer and noncancerous tissue in vaginal fluid. Based on this research, she hopes to develop an affordable tampon-based home screening test for endometrial, ovarian and cervical cancers, as well as high-risk HPV .

"This is exciting because this type of screening test can be used by people living in rural areas,” says Dr. Weroha. “If it's successful, it could help healthcare professionals identify ovarian and other gynecologic cancers sooner, when they're more treatable, in people living in all the communities we serve.”

A gynecologic oncologist and clinical trials can help you get the best possible treatment.

If you've been diagnosed with ovarian cancer, Dr. Weroha recommends making an appointment with a gynecologic oncologist . "A gynecologic oncologist will be up to date on the current treatment recommendations and the management of side effects. That's important," he says. "Once the plan is set, however, any medical oncologist could implement it.”

Dr. Weroha also recommends newly diagnosed patients ask their care teams if they are candidates for PARP inhibitors, mirvetuximab or clinical trials. "PARP inhibitors and mirvetuximab are newer treatments that could influence the outcome of your overall treatment. Always ask about clinical trials because when ovarian cancer recurs, there is no treatment so good that we can stop looking for something better," he says. "There is a very realistic hope that if your cancer were to come back, we would have something better that we don't have today."

Learn more about ovarian cancer and find a clinical trial at Mayo Clinic.

Join the Gynecologic Cancers Support Group on Mayo Clinic Connect , an online community moderated by Mayo Clinic for patients and caregivers.

Join the next virtual Gynecologic Cancer Support Meeting: Women of S-Teal . Monthly meetings are held every second Monday from 5:30 to 6:30 p.m. ET.

Also, read these articles:

A step toward detecting endometrial cancer earlier
Harnessing the immune system to fight ovarian cancer
Life after ovarian cancer: Coping with side effects, fear of recurrence, and finding support
New surgical method for ovarian cancer lights up lesions
Is a cancer clinical trial right for me?
New chemotherapy approach for late-stage cancers

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Ovarian Cancer Research Highlights

Ovarian cancer causes more deaths in women living in the United States than any other cancer of the female reproductive system. The American Cancer Society’s (ACS) research programs help find answers to critical questions:

How can ovarian cancer be diagnosed early?
How can the risk of developing ovarian cancer be lowered?
Are there more effective treatments?
What could help survivors have a better quality of life?

We continue to fund research to help save more lives in the future.

Ovarian Cancer Still Causes the Most Deaths from Gynecological Cancer

About 90% of cases are epithelial ovarian cancer, and most of those cases are high-grade serous tumors, which have the fewest established risk factors and the worst prognosis.

Risk & Prevention Studies

We've learned more about the risk of developing ovarian cancer.

Thanks to CPS-II and CPS-3 participants!

The ACS’s CPS-II Nutrition Cohort is part of the Collaborative Group on Epidemiological Studies of Ovarian Cancer. This group helped establish the increased risk for ovarian cancer in women with excess body weight and the decreased risk of ovarian cancer for women who use oral contraceptives.”

Alpa Patel, PhD

Senior Vice President Population Science

American Cancer Society

asian woman wearing turquoise patterned shirt

Ovarian Cancer Statistics on Age

It's rare for women younger than 40 to have ovarian cancer.

Half of all ovarian cancers are found in women age 63 or older.

Featured Term: Biomarker

A measurable molecular, genetic, chemical, or physical characteristic in the blood or other bodily fluids, such as sweat and tears, that is a sign of a normal or abnormal process or of a health condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease.

Featured Term: Susceptibility Biomarkers

A biomarker that signals the potential, or risk, a person has to develop a disease before they have symptoms. For instance, low-density lipoprotein (LDL) cholesterol is a susceptibility biomarker for heart disease.

Early Detection Studies

Glowing “fingerprint” from a blood test may find ovarian cancer early.

Machine learning and tiny glowing nanosensors enable the detection of ovarian cancer from a blood test.

Ovarian Cancer May Start in Fallopian Tube Cells

By studying fallopian tube cells from cancer-free women, researchers learned more about the origin of the most deadly type of ovarian cancer.

A New Gene Is Linked with the Deadliest Type of Ovarian Cancer

Researchers develop a new genetically engineered mouse ovarian cancer model to explore potential new drug targets to treat epithelial ovarian cancer.

Ovarian Cancer Statistics on Racial Disparities

the rank Black people have on a 1-to-5 scale (with 5 as the lowest) for the incidence rate of ovarian cancer based on race and ethnicity

the rank Black people have on a 1-to-5 scale (with 5 as the lowest) for the death rate of ovarian cancer based on race and ethnicity

the rank American Indian and Alaska Native people have on a 1-to-5 scale (with 5 as the lowest) for incidence rate AND death rate for ovarian cancer based on race and ethnicity

Treatment Studies

New gene-testing tools may personalize ovarian cancer care.

Researchers say using next-generation sequencing technology as a diagnostic tool may increase precision treatment plans for people with ovarian cancer.

Chromosome-Hoarding Ovarian Cancer Cells May Help Treatment

Using new CRISPR tools, researchers learn extra chromosomes promote tumor growth and paradoxically may help activate some treatments.

Testing Nanoparticles to Deliver Drugs to Mice with Ovarian Cancer

Researchers find that drugs successfully attack metastasized ovarian tumors when they're given via teeny nanoparticles injected directly into the abdomen.

Ovarian Cancer Advocacy

Listen to Vanessa's story: She's an ovarian cancer survivor and now advocates to help other survivors have access to care.

ACS Ovarian Cancer Research News

Sitting Too Much Increases Cancer Risk in Women

Statistics (Downloadable PDFs)

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Special Section Ovarian Cancer

Useful Links

Ovarian Cancer - ACS Cancer Statistics Center

Glossary for Nonscientists

We Fund Ovarian Cancer Researchers Across the US

The ACS funds scientists who conduct research about ovarian cancer at medical schools, universities, research institutes, and hospitals throughout the United States. We use a rigorous and independent peer review process to select the most innovative research projects proposals to fund.

These grant statistics are as of July 15, 2024.

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Ovarian Cancers: Evolving Paradigms in Research and Care (2016)

Chapter: 1 introduction and background.

Introduction and Background

Although recent years have seen many promising advances in cancer research, there remain surprising gaps in the fundamental knowledge about and understanding of ovarian cancer. Researchers now know that ovarian cancer, like many other types of cancer, should not be thought of as a single disease; instead, several distinct subtypes exist with different origins, different risk factors, different genetic mutations, different biological behaviors, and different prognoses, and much remains to be learned about them. For example, researchers do not have definitive knowledge of exactly where these various ovarian cancers originate and how they develop. Such unanswered questions have impeded progress in the prevention, early detection, treatment, and management of ovarian cancers. In particular, the failure to achieve major reductions in ovarian cancer morbidity and mortality during the past several decades is likely due to several factors, including

A lack of research focusing on specific disease subtypes;
An incomplete understanding of genetic and nongenetic risk factors;
An inability to develop and validate effective screening and early detection tools;
Inconsistency in the delivery of the standard of care;
Limited evidence-based personalized medicine approaches tailored to the disease subtypes and other tumor characteristics; and
Limited attention paid to research on survivorship issues, including supportive care with long-term management of active disease.

The symptoms of ovarian cancers can be nonspecific and are often not seen as indicating a serious illness by women or their health care providers until the symptoms worsen, at which point the cancer may be widespread and difficult to cure. The fact that these cancers are not diagnosed in many women until they are at an advanced stage is a major factor contributing to the high mortality rate for ovarian cancer, especially for women with high-grade serous carcinoma (HGSC)—the most common and lethal subtype. Indeed, roughly two-thirds of women with ovarian cancer are diagnosed with an advanced-stage cancer or with a cancer that has not been definitively staged, and the 5-year survival rate for these women is less than 30 percent (Howlader et al., 2015). Although many ovarian cancers respond well to initial treatment, including the surgical removal of grossly visible tumor (cytoreduction) and chemotherapy, the vast majority of the tumors recur. Recurrent ovarian cancers may again respond to further treatment, but virtually all of them will ultimately become resistant to current drug therapies.

Finally, less emphasis has been placed on research that focuses on how to improve therapeutic interventions by subtype or on how to reduce the morbidity of ovarian cancers. Little emphasis has been placed on understanding survivorship issues and the supportive care needs of women with ovarian cancer, including management of the physical side effects of treatment (including both initial and chronic, ongoing therapies) and addressing the psychosocial effects of diagnosis and treatment. The lasting impact of a diagnosis of ovarian cancer and its related treatment can be significant both for the women who experience recurrent disease and for the women who experience long (or indefinite) periods of remission. This report gives an overview of the state of the science in ovarian cancer research, highlights the major gaps in knowledge in that field, and provides recommendations that might help reduce the incidence of and morbidity and mortality from ovarian cancers by focusing on promising research themes and technologies that could advance risk prediction, early detection, comprehensive care, and cure.

STUDY CHARGE AND APPROACH

In spite of their high mortality rates, ovarian cancers often do not receive as much attention as other cancers. In part, this is because ovarian cancers are relatively uncommon. Furthermore, ovarian cancer has been called a “silent killer” because researchers once believed that there were no perceptible symptoms in the earlier stages of the disease (Goff, 2012). However, more recent research has shown that most women diagnosed with ovarian cancer report symptoms such as bloating, pelvic or abdominal pain, and urinary symptoms, and many women recall having these symptoms

for an extended period of time before diagnosis (Goff et al., 2000, 2004). Often, due to the nonspecific nature of ovarian cancer symptoms, patients and physicians do not recognize these early symptoms as indicative of ovarian cancer (Gajjar et al., 2012; Jones et al., 2010; Lockwood-Rayermann et al., 2009).

In this context, in 2006 the U.S. Congress passed the Gynecologic Cancer Education and Awareness Act of 2005, 1 which amended the Public Health Service Act (42 U.S.C. 247b-17) to direct the secretary of the U.S. Department of Health and Human Services to launch a campaign to “increase the awareness and knowledge of health care providers and women with respect to gynecologic cancers.” The law is commonly known as Johanna’s Law in memory of Johanna Silver Gordon, a public school teacher from Michigan who died from late-stage ovarian cancer (Twombly, 2007). The law was reauthorized in 2010, 2 and, as part of the Consolidated Appropriations Act of 2014, Congress directed the Centers for Disease Control and Prevention (CDC) to use funds from Johanna’s Law to perform a review of the state of the science in ovarian cancer. 3

Study Charge

In the fall of 2014, with support from the CDC, the Institute of Medicine (IOM) formed the Committee on the State of the Science in Ovarian Cancer Research to examine and summarize the state of the science in ovarian cancer research, to identify key gaps in the evidence base and challenges to addressing those gaps, and to consider opportunities for advancing ovarian cancer research (see Box 1-1 ). The committee determined that the best way to facilitate progress in reducing morbidity and mortality would be to identify the research gaps that were most salient and that, if addressed, could affect the greatest number of women.

The committee was also asked to consider ways to translate and disseminate new findings and to communicate these findings to all stakeholders. This report, therefore, not only describes evidence-based approaches to translation and dissemination, but it also suggests strategies for communicating those approaches.

________________

1 Gynecologic Cancer Education and Awareness Act of 2005, Public Law 475, 109th Cong., 2nd sess. (January 12, 2007).

2 To reauthorize and enhance Johanna’s Law to increase public awareness and knowledge with respect to gynecologic cancers, Public Law 324, 111th Cong., 2nd sess. (December 22, 2010).

3 Explanatory statement submitted by Mr. Rogers of Kentucky, Chairman of the House Committee on Appropriations regarding the House amendment to the Senate amendment on H.R. 3547, consolidated... , 113th Cong., 2nd sess., Congressional Record 160, no. 9, daily ed. (January 15, 2014):H 1035.

BOX 1-1 Statement of Task

An ad hoc committee under the auspices of the Institute of Medicine will review the state of the science in ovarian cancer research and formulate recommendations for action to advance the field. The committee will:

Summarize and examine the state of the science in ovarian cancer research;
Identify key gaps in the evidence base and the challenges to addressing those gaps;
Consider opportunities for advancing ovarian cancer research; and
Examine avenues for translation and dissemination of new findings and communication of new information to patients and others.

The committee will make recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of and morbidity and mortality from ovarian cancer.

The committee emphasizes that its charge was to focus on research in ovarian cancer and, particularly, to focus on the gaps in the evidence base that, if addressed, would have the greatest impact on the lives of women diagnosed with or at risk for ovarian cancer. The committee did not explore issues affecting the care of women with ovarian cancer (e.g., health insurance coverage and policy issues) in depth. For example, while the regulatory process for drug approval is interconnected with the clinical trial enterprise (e.g., the design of clinical trials may determine what data are gathered and, in turn, affect the approval process), a full examination of issues related to the approval of new drugs was beyond the scope of this report. Furthermore, it was outside the scope of this report to fully evaluate specific research programs in ovarian cancer. In addition, this report does not offer an exhaustive cataloguing of every actor engaged in ovarian cancer research, nor does it detail every effort made by stakeholders to engage in dissemination and implementation efforts. Rather, the examples given in this report are meant to highlight the efforts being made, recognizing there are many other similar efforts.

Finally, the committee focused as much as possible on the research gaps and the challenges to addressing those gaps that are unique to ovarian cancer. However, those research gaps and challenges that are common to all types of cancer research, or even to all health care research, are described as appropriate. For example, while the clinical trials system is extremely important to the ovarian cancer research enterprise, many of the outstanding

questions and concerns related to the clinical trials system are shared with all types of cancer research and could not be explored or discussed in detail. Therefore, the committee turned to previous IOM reports specific to the clinical trials system in general for guidance, and then considered aspects of the system that are particularly relevant for ovarian cancer research.

Study Approach

The study committee included 15 members with expertise in ovarian cancer, gynecologic oncology, gynecologic pathology, gynecologic surgery, molecular biology, cancer genetics and genomics, genetic counseling, cancer epidemiology, immunology, biostatistics, bioethics, advocacy, survivorship, and health communication. (See Appendix E for biographies of the committee members.)

A variety of sources informed the committee’s work. The committee met in person four times, and during two of those meetings it held public sessions to obtain input from a broad range of relevant stakeholders. In addition, the committee conducted extensive literature reviews, reached out to a variety of public and private stakeholders, and commissioned one paper.

The committee encountered a number of challenges. In some cases, it found itself limited by what was available in the published literature. At other times, it was challenged by the use of different methodologies for the classification of ovarian cancers in the research literature. For instance, many studies in the literature consolidate all types of ovarian cancer instead of studying and reporting them by subtype. In its review of the evidence, the committee discerns, where possible, whether the reported findings apply to ovarian cancers as a whole or to particular subtypes. One other major challenge to reviewing and summarizing the evidence base on ovarian cancer, particularly in summarizing the epidemiology by subtype, was the way that the grading, classification, and nomenclature for ovarian cancers have varied over the years.

In order to guide its deliberative process, the committee chose to make recommendations about research gaps based on the continuum of cancer care (see Figure 1-1 ). The committee focused on cross-cutting research areas critical to each phase of the continuum: the basic biology of ovarian cancers, innovative clinical trial design, intervention development, methods to reduce practice-related disparities, and supportive care research and practice. Finally, the committee considered evidence and strategies for the dissemination and implementation of knowledge across all of these domains.

DEFINITIONS OF KEY TERMS

This section provides definitions of several key terms that are relevant to this report, and also provides an explanation of how the committee

FIGURE 1-1 Framework for research in ovarian cancer. NOTE: Colored figures represent phases of the ovarian cancer care continuum where research can be focused. Black boxes indicate critical areas of ongoing cross-cutting research that span these phases.

selected terms for consistency throughout the report. A glossary including more terms is provided in Appendix B , and a list of key acronyms is included in Appendix A .

Target Population

This report is concerned with women with ovarian cancers. However, the committee recognizes that there is a small subpopulation of transgender men who may be at risk for ovarian cancers, particularly due to the use of testosterone therapy (Dizon et al., 2006; Hage et al., 2000).

Basic Cancer Terminology

The terms “cancer,” “carcinoma,” and “tumor” can be confused or interchanged at times. Cancer is “a term for diseases in which abnormal cells divide without control and can invade nearby tissues,” while a tumor (which can be cancerous or noncancerous) is “an abnormal mass of tissue that results when cells divide more than they should or do not die when they should” (NCI, 2015d). Carcinomas are cancers that “begin in the skin or in tissues that line or cover internal organs” (i.e., arising from epithelial cells) (NCI, 2015d). As was noted previously, this report focuses on ovarian carcinomas, because they are the most common and most lethal of the ovarian cancer subtypes.

While the committee endeavored to focus on carcinomas wherever possible, there were times when that was not possible, and the terms “cancer” and “tumor” are used when appropriate. For example, many studies are based on ovarian cancers collectively and do not analyze data based on the subtypes. The committee also uses the term “tumor” when discussing the physical mass itself. Finally, although the term “ovarian cancer” technically represents an array of disease subtypes, the committee refers to the disease in the plural form (i.e., “ovarian cancers”) whenever appropriate in order to emphasize the heterogeneity of the disease and all its subtypes.

When ovarian cancer reappears in a woman, it is usually referred to as “relapsed” or “recurrent” disease. The National Cancer Institute (NCI) defines cancer recurrence as “cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body” (NCI, 2015d). Noting that a cancer that has recurred is also called “relapsed cancer,” the NCI defines relapse as “the return of a disease or the signs and symptoms of a disease after a period of improvement.” In this report, for consistency the committee uses only the terms “recurrent” or “recurrence”—and not “relapsed” or “relapse”—but

it recognizes that there may be subtle differences, preferences, or interpretations in the use of the two terms.

DEFINING AND CLASSIFYING OVARIAN CANCERS

“Ovarian cancer” is a generic term that can be used for any cancer involving the ovaries. The ovaries are composed of several different cell types, including the germ cells, specialized gonadal stromal cells (e.g., granulosa cells, theca cells, Leydig cells, and fibroblasts), and epithelial cells; ovarian cancers can arise from any of these cell types. Ovarian cancers with epithelial differentiation (carcinomas) account for more than 85 percent of ovarian cancers and are responsible for most ovarian cancer–related deaths (Berek and Bast, 2003; Braicu et al., 2011; SEER Program, 2015; Seidman et al., 2004). Consequently, this report will focus on the biology of ovarian carcinomas, while recognizing that although other, less common types of ovarian malignancies do exist, they are responsible for a smaller fraction of ovarian cancer–related deaths.

As with ovarian cancers in general, ovarian carcinomas are quite heterogeneous and come in a variety of different tumor types (see Figure 1-2 ). The major ovarian carcinoma subtypes are named according to how closely the tumor cells resemble normal cells lining different organs in the female genitourinary tract. Specifically, serous, endometrioid, and a subset

FIGURE 1-2 Percentage of cases by major ovarian carcinoma subtype. NOTE: Other* refers to mixed or transitional carcinomas where it is not possible to categorize to a single subtype. SOURCE: Gilks et al., 2008; Seidman et al., 2003, 2004.

of mucinous carcinomas exhibit morphological features that are similar to normal epithelial cells in the fallopian tube, endometrium, and endocervix, respectively. Furthermore, clear cell carcinomas resemble cells seen in the gestational endometrium (Scully et al., 1999).

Over the past several years, researchers have developed a streamlined classification scheme in which the majority of ovarian carcinomas can be divided into five types:

Endometrioid carcinoma (EC),
Clear cell carcinoma (CCC),
Low-grade serous carcinoma (LGSC), and
Mucinous carcinoma (MC) (Gurung et al., 2013; Kalloger et al., 2011).

Some researchers have offered an even simpler classification with a scheme in which ovarian carcinomas are divided into Type I and Type II tumors based on shared features (Shih and Kurman, 2004). In this scheme, Type I carcinomas are low-grade, relatively unaggressive, and genetically stable tumors that often arise from recognizable precursor lesions such as endometriosis or benign tumors and frequently harbor somatic mutations that deregulate specific cell signaling pathways or chromatin remodeling complexes. ECs, CCCs, MCs, and LGSCs are considered Type I tumors and are often characterized by KRAS, BRAF , or PTEN mutations. Type II carcinomas are high-grade, biologically aggressive tumors from their inception, with a propensity for metastasis from small, even microscopic, primary lesions. HGSCs represent the majority of Type II tumors and are characterized by the mutation of TP53 and frequent mutations of genes (e.g., BRCA1 and BRCA2 ) that lead to homologous recombination defects (Pennington et al., 2014).

Because the data collected thus far provide compelling evidence that each of the various Type I tumors has distinct biological and molecular features, these tumors will be referred to by their specific histologic type throughout the remainder of this report. However, the Type I and Type II terminology will be used where necessary, most often in referring to studies conducted using this classification scheme. Furthermore, because the majority of ovarian carcinomas are HGSCs, and HGSCs are the subtype with the worst prognosis, this report will primarily focus on this subtype. When referring to historical or large-scale epidemiologic studies of ovarian cancer for which the tumor subtypes were not specified, readers can reasonably assume that most of the tumors were HGSCs.

After being classified by subtype, tumors are usually also assigned a grade, based on how closely the tumor cells resemble their normal counter-

parts. Both two-grade and three-grade systems have been applied in various situations; in both types of systems, the lower-grade tumors more closely resemble normal cells than the higher-grade tumors (Malpica et al., 2004; Silverberg, 2000).

OVARIAN CANCER PATTERNS AND DEMOGRAPHICS 4

Although ovarian cancer is relatively rare, it is one of the deadliest cancers. It was estimated that more than 21,000 women in the United States would receive a diagnosis of an ovarian cancer in the year 2015 5 (Howlader et al., 2015). This represents almost 12 new cases for every 100,000 women and 2.6 percent of all new cancer cases in women in the United States. Nearly 200,000 women in the United States are living with ovarian cancer in any given year, and approximately 1.3 percent of all American women will be diagnosed with ovarian cancer at some point in their lives, which qualifies ovarian cancer as a rare disease as defined by the National Institutes of Health (NIH) Genetic and Rare Diseases Information Center (NIH, 2015a). Still, according to estimates, more than 14,000 American women will have died from ovarian cancer in 2015, which corresponds to approximately 7.7 deaths per 100,000 women and 5.1 percent of all cancer deaths among American women (ACS, 2015; Howlader et al., 2015). Despite its relatively low incidence, ovarian cancer is the fifth leading cause of cancer deaths among U.S. women and the eighth leading cause of women’s cancer deaths worldwide (Ferlay et al., 2015; Howlader et al., 2015). By comparison, breast cancer is more common—among American women the estimated number of new cases of breast cancer each year is 10 times the number of new cases of ovarian cancer—but ovarian cancer is more deadly, with a death-to-incidence ratio that is more than three times higher than for breast cancer (Howlader et al., 2015) (see Figure 1-3 ).

The survival rate for ovarian cancer is quite low. For 2005 to 2011, the 5-year survival rate in the United States was just 45.6 percent. By contrast, the 5-year survival rate in the United States for the same period was nearly 90 percent for breast cancer, more than 80 percent for endometrial cancer, and nearly 70 percent for cervical cancer. However, given the typical course of initial remission and subsequent recurrence for women with ovarian cancer, the 5-year survival metric may not reflect the overall disease course. At advanced stages, MCs and CCCs in particular have poorer prognoses and survival rates than other carcinoma subtypes (Mackay et al., 2010).

4 Terminology to describe race and ethnicity reflects the terminology used in the original sources.

5 Because historical epidemiologic data typically combine the multiple types of ovarian cancer, they are discussed as a single disease in this discussion of epidemiology.

FIGURE 1-3 The ratio between the death and incidence rates for ovarian, breast, endometrial, and cervical cancers per 100,000 women in the United States, 2008–2012. SOURCE: Howlader et al., 2015.

The incidence of ovarian cancer has declined slightly since the mid-1970s, when the incidence was approximately 16 new cases per 100,000 women (Howlader et al., 2015). Mortality from ovarian cancer has also declined—from 9.8 deaths per 100,000 women in 1975 to 7.4 deaths per 100,000 women in 2012. However, the decline in mortality is relatively small when compared to reductions in death rates achieved for most other female gynecological cancers and for breast cancer in women. For example, the death rate from breast cancer fell by one-third between 1975 and 2012, from 31.4 deaths per 100,000 women to 21.3 deaths per 100,000, and the death rate from cervical cancer dropped by more than half during that same period, from 5.6 deaths per 100,000 women to 2.3 deaths per 100,000.

Among women who were diagnosed with ovarian cancer between 1975 and 1977, only 36 percent lived 5 years or more, while nearly half (46 percent) of women diagnosed with ovarian cancer between 2005 and 2007 lived at least 5 years beyond their diagnosis (Howlader et al., 2015). However, that improvement in survival rates was driven primarily by improvements in survival among white women; survival rates decreased (from 42 to 36 percent) over the same period for black women (ACS, 2015; also see section Race and Ethnicity later in this chapter).

Stage Distribution

Ovarian cancer’s high mortality and low survival rates can be attributed in part to the fact that it is rarely diagnosed at an early stage. Indeed, 60 percent of women are diagnosed with advanced disease, when the cancer has already spread beyond the ovary to distant organs or lymph nodes (Howlader et al., 2015). In comparison, as seen in Figure 1-4 , other female cancers are more commonly diagnosed during the localized or regional stages.

The relatively late stage of diagnosis for ovarian cancer is particularly important because survival is highly correlated with the stage at diagnosis (see Figure 1-5 ). While the 5-year survival rate is 45.6 percent overall, it is substantially higher for women diagnosed while the cancer is still at the localized stage (92.1 percent) or the regional stage (73.2 percent), and it is substantially lower for women diagnosed at the distant stage (28.3 percent) (ACS, 2015; Howlader et al., 2015). Survival is lowest among women who receive an unstaged ovarian cancer diagnosis (22.9 percent).

White and black women show similar patterns of stage distribution (see Figure 1-6 ). However, there is a difference in stage of diagnosis in women

FIGURE 1-4 Distribution (percentage) of stage of diagnosis for cancers of the breast, endometrium, cervix, and ovary among U.S. women, 2005–2011. SOURCE: Howlader et al., 2015.

FIGURE 1-5 Five-year relative survival (percentage) from ovarian cancer by stage at diagnosis among U.S. women, 2005–2011. SOURCE: Howlader et al., 2015.

FIGURE 1-6 Stage distribution (percentage of cases) at diagnosis among white and black U.S. women diagnosed with ovarian cancer, 2003–2009. SOURCE: Howlader et al., 2015.

of different ages, with women younger than age 65 tending to be diagnosed at earlier stages than women older than age 65 (see Figure 1-7 ).

Ovarian cancer incidence increases with age, with a sharp increase in the rate beginning in the mid-40s (see Figure 1-8 ). From 2008 to 2012, nearly 88 percent of all new cases of ovarian cancer occurred among women ages 45 and older, with 69 percent of cases among women ages 55 and older, and the average age at diagnosis was 63 years. A half-century ago, most cases occurred among women between the ages of 35 and 63, and the average age at diagnosis was 48.5 years (Munnell, 1952).While the age-adjusted incidence rate for ovarian cancer among all women is nearly 12 cases per 100,000 women, the rate varies sharply with age, with women younger than age 65 having an incidence rate of 7.5 cases per 100,000 women while women 65 years old and older have an incidence rate of more than 42 cases per 100,000 women (Howlader et al., 2015).

Mortality rates also increase sharply with age. The death rate for women aged 65 and older is approximately 13 times that of women less than age 65 (see Figure 1-9 ). Furthermore, while mortality rates have de-

FIGURE 1-7 Stage distribution (percentage of cases) at diagnosis among women diagnosed with ovarian cancer by age, 2003–2009. SOURCE: Howlader et al., 2015.

FIGURE 1-8 Age-adjusted incidence of ovarian cancer per 100,000 women in the United States by age group. SOURCE: SEER Program, 2015.

FIGURE 1-9 Trends in age-adjusted death rates from ovarian cancer per 100,000 women in the United States by age group, 1975–2012. SOURCE: Howlader et al., 2015.

clined overall in the past 40 years, most of this decline is attributable to decreases in mortality among women diagnosed with ovarian cancer less than age 65 (ACS, 2015; Howlader et al., 2015).

Race and Ethnicity

The patterns of ovarian cancer incidence and mortality differ substantially among women of different races and ethnic backgrounds (see Figure 1-10 ). Whites have the highest incidence of ovarian cancer, followed by Hispanics, American Indian/Alaska Natives, blacks, and Asian/Pacific Islanders (ACS, 2015; Howlader et al., 2015; Singh et al., 2014). The 5-year survival rate is highest among Asian/Pacific Islanders, followed by Hispanics, whites, American Indian/Alaska Natives, and blacks, while mortality rates are highest among whites, followed by blacks, Hispanics, American Indian/Alaska Natives, and Asian/Pacific Islanders. A particularly dramatic contrast can be seen between black and Asian/Pacific Islander women. While the two groups are similar in having low incidence rates, black women have the second-highest mortality rates and the lowest survival rates, while Asian/Pacific Islanders have the lowest mortality and the highest survival rates. The incidence of ovarian cancer, particularly HGSC, is higher than average in women of Ashkenazi Jewish ancestry, in part because of the higher prevalence of deleterious mutations in cancer-predisposition genes such as BRCA1 and BRCA2 among these women (ACS, 2015; Moslehi et al., 2000).

FIGURE 1-10 Age-adjusted ovarian cancer incidence and mortality per 100,000 U.S. women by race and ethnicity, 2008–2012. SOURCE: Howlader et al., 2015.

Furthermore, the variations in the incidence rates of ovarian cancer by race and ethnicity change as women age (see Figure 1-11 ). For example, whites and Asian/Pacific Islanders have similar incidence rates until around age 50, when their incidence rates begin to diverge. White women aged 45–49 have an age-specific incidence rate of 15.1 cases per 100,000, and Asian/Pacific Islanders of the same age group have a very similar rate of 15.5 cases per 100,000. By contrast, white women aged 80–84 have an incidence rate of 50.8 cases per 100,000, while Asian/Pacific Islanders of the same age group have a dramatically lower rate of 30.1 cases per 100,000.

Historical trends also show considerable variations by race. Between 2003 and 2012, mortality rates decreased significantly among whites and Hispanics, while declines in mortality among blacks, Asian/Pacific Island-

FIGURE 1-11 Age-specific incidence rates of ovarian cancer per 100,000 women in the United States by race/ethnicity and age at diagnosis, 2008–2012. NOTE: Rates for American Indian/Alaska Natives are only displayed for ages 50 through age 69, because the number of cases in other age groups were less than 16 per age group. SOURCE: SEER Program, 2015.

ers, and American Indian/Alaskan Natives were not statistically significant (Howlader et al., 2015). Moreover, while survival rates have increased among women overall and among white women since the mid-1970s, survival rates have declined slightly among black women (see Figure 1-12 ). Furthermore, although black women had higher rates of survival compared to white women and to women overall in 1975, by the mid-1980s survival rates had begun to reverse, such that black women now have lower survival rates than white women and women of all races overall even despite gains in survival among blacks in the 1990s (ACS, 2015).

In the United States, there are slight geographic variations in ovarian cancer incidence, but these variations are not significant (Howlader et al., 2015; Ries et al., 2007). However, the differences in mortality from state to state are significant. In the United States, from 2008 to 2012 the death rate for ovarian cancer was 7.7 deaths per 100,000 women. During that same period, the age-adjusted death rates by state ranged from a low of 5.3 deaths per 100,000 women in Hawaii to a high of 9.0 deaths per 100,000 women in Oregon (Howlader et al., 2015). Despite the wide variation

FIGURE 1-12 Trends in 5-year relative survival rates (percentage) for ovarian cancer among U.S. women by race, 1975–2011. SOURCE: Howlader et al., 2015.

across the states, only Alabama, Oregon, Pennsylvania, and Washington have significantly higher rates, statistically speaking, than the United States as a whole, while only Florida, Hawaii, and Texas have significantly lower rates than the national average.

Ovarian cancer incidence and mortality also vary internationally, with incidence and mortality rates being higher in more developed regions than in less developed regions (Ferlay et al., 2015).

Aside from genetics (e.g., the higher proportion of mutations in cancer-predisposition genes among Ashkenazi Jewish women), the reasons behind the racial and ethnic differences in outcomes are unknown, but they might be explained in part by other variables such as differences in access to health care or the quality of that care (Baicker et al., 2005; IOM, 2003, 2012). Similarly, the reasons behind geographic variation in the demographics of ovarian cancer are unknown, and might be explained by other variables such as race and ethnicity (e.g., the higher proportion of Asian and Pacific Islanders in Hawaii) or differences in access to health care or the quality of that care in different geographic regions (Baicker et al., 2005; IOM, 2003, 2012). (See Chapter 4 for more on access and standards of care for women with ovarian cancer.) Overall, as noted previously, reporting on the demographics and epidemiology of ovarian cancer is challenging because of the fact that most of the data sources aggregate the various subtypes, and even when the data are reported by subtype, differences in the grading, classification, and nomenclature of the subtypes create challenges in summarizing and comparing data.

THE LANDSCAPE OF STAKEHOLDERS IN OVARIAN CANCER RESEARCH

Many public and private organizations are involved in funding, supporting, and carrying out ovarian cancer research, and they are involved in a variety of ways. The research is sometimes focused on ovarian cancers exclusively, but it sometimes looks at broader populations (e.g., women with gynecologic cancers). A complete cataloguing of every stakeholder in ovarian cancer research and of their individual efforts is beyond the scope of this report. Instead, this section offers an overview of the wide range of stakeholders and highlights the areas of ovarian cancer research that are getting the most attention and the methods used by stakeholders to communicate about new findings in ovarian cancer research.

Federal Stakeholders

While there are a number of different federal stakeholders in ovarian cancer research, the CDC, the U.S. Department of Defense (DoD), and the NIH (and the NCI in particular) are collectively responsible for the majority of the funding for ovarian cancer research at the federal level. The sections below give an overview of the funding levels and focus areas for these agencies. Where possible, the areas of focus are presented in alignment with the Common Scientific Outline (CSO), an international classification system used by cancer researchers to compare research portfolios. The CSO consists of seven broad areas of interest:

Etiology (causes of cancer);
Prevention;
Early detection, diagnosis, and prognosis;
Cancer control, survivorship, and outcomes research; and
Scientific model systems (DoD, 2015b).

Centers for Disease Control and Prevention

The CDC conducts and supports studies, often in collaboration with partners, to “develop, implement, evaluate, and promote effective cancer prevention and control practices” (CDC, 2015). In general, the CDC approaches cancer by monitoring cancer demographics (surveillance), by conducting research and evaluation, by partnering with other stakeholders to help translate evidence, and by developing educational materials (CDC, 2015). Most of the CDC’s work in ovarian cancer is performed through its Division of Cancer Prevention and Control. 6 Since fiscal year (FY) 2000, the CDC has received about $5 million annually in congressional appropriations to support its Ovarian Cancer Control Initiative. In addition, in 2008 the CDC started receiving funds under Johanna’s Law to improve communication with women regarding gynecologic cancers. The CDC’s Inside Knowledge 7 campaign works to raise awareness about cervical, ovarian, uterine, vaginal, and vulvar cancers. Between 2010 and 2014, ads produced for the Inside Knowledge campaign were seen or heard around 3.5 million times and were worth a total of $136 million in donated ad value (CDC, 2014).

6 For more information, see http://www.cdc.gov/cancer/dcpc/about (accessed July 21, 2015).

7 For more information, see http://www.cdc.gov/cancer/knowledge (accessed September 1, 2015).

U.S. Department of Defense

The DoD’s Ovarian Cancer Research Program (OCRP) 8 received congressional appropriations from FY 1997 to FY 2014 totaling $236.45 million and received another $20 million in appropriations for FY 2015 (DoD, 2015a). Since the inception of the DoD OCRP, more than 130 ovarian cancer survivors have taken part in efforts to establish the OCRP’s priorities and research award mechanisms, and they have helped choose the research to be funded. From FY 1997 through FY 2013, the OCRP funded 313 awards in a variety of areas (see Figure 1-13 ). These awards show a focus on biology, treatment, and early detection, diagnosis, and prognosis. OCRP’s research priorities include understanding the precursor lesions, microenvironment, and pathogenesis of all types of ovarian cancer; developing and improving the performance and reliability of screening, diagnostic approaches, and treatment; developing or validating models to study initiation and progression; investigating tumor response to therapy; and enhancing the pool of ovarian cancer scientists (DoD, 2015a).

National Institutes of Health

The NCI of the NIH has initiated several activities to advance ovarian cancer research with intramural and extramural funding. In the past, five ovarian cancer–specific specialized programs of research excellence (SPOREs) in the United States conducted ovarian cancer research in early detection, imaging technologies, risk assessment, immunosuppression, and novel therapeutic approaches (NCI, 2015e). The NCI currently lists four active SPOREs for ovarian cancer.

The NCI is involved in ovarian cancer research in a variety of other ways. For example, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) is trying to understand the molecular basis of cancer in order to help improve the diagnosis, treatment, and prevention of cancer (NCI, 2015b). To accomplish these goals, CPTAC is using the data collected by The Cancer Genome Atlas (TCGA) analysis of ovarian tumors. The NCI has also supported a follow-up of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to analyze the biological material and risk factor information in order to better understand the risks and identify early biomarkers, including biomarkers for ovarian cancers. (See Chapter 3 for more on the PLCO Cancer Screening Trial.)

8 For more information, see http://cdmrp.army.mil/ocrp (accessed July 21, 2015).

FIGURE 1-13 Areas of ovarian cancer research funded by OCRP, FY 1997–2011. SOURCE: DoD, 2015b.

Overall, the NCI supported $100.6 million in research 9 related to ovarian cancer in FY 2013 while providing $559.2 million for breast cancer research, $63.4 million for cervical cancer research, and $17.8 million for endometrial cancer research (NCI, 2015g). However, the research projects listed as being related to ovarian cancer are not necessarily limited to ovarian cancer, and they include studies of multiple cancers (including ovarian cancer) or areas of cross-cutting research related to ovarian cancer. Fur-

9 The NCI notes that “the estimated NCI investment is based on funding associated with a broad range of peer-reviewed scientific activities” (NCI, 2015g). The NCI research portfolio for ovarian cancer may be found at http://fundedresearch.cancer.gov/nciportfolio/search/get?site=Ovarian+Cancer&fy=PUB2013 (accessed December 2, 2015).

thermore, data collected by the DoD 10 through the International Cancer Research Partnership indicates that the funded amount is significantly less when considering only new grants awarded by the NCI each year. Only 52 projects involving ovarian cancer research totaling $33.4 million were started in 2010, 58 new projects totaling $20.4 million in 2011, and 52 new projects totaling $16.3 million in 2012 (ICRP, 2015). Figure 1-14 shows that, like the DoD, the NCI portfolio for ovarian cancer research focuses primarily on treatment, biology, and early detection, diagnosis, and prognosis.

The Office of Cancer Survivorship (OCS), 11 part of the Division of Cancer Control and Population Sciences at the NCI, “works to enhance the quality and length of survival of all persons diagnosed with cancer and to minimize or stabilize adverse effects experienced during cancer survivorship. The office supports research that both examines and addresses the long- and short-term physical, psychological, social, and economic effects of cancer and its treatment among pediatric and adult survivors of cancer and their families” (NCI, 2014).

Figure 1-15 shows the areas of cancer survivorship research expertise at the NCI. As of October 2015, the Division of Cancer Control and Population Sciences had two open funding opportunities for general cancer survivorship research: one focused on the efficacy and impact of care planning, and the other examined the effects of physical activity and weight control interventions on cancer prognosis and survival (NCI, 2015a). Neither of these grant opportunities specified a focus on ovarian cancer survivorship.

Private Stakeholders

A wide variety of private stakeholders are engaged in ovarian cancer research, including professional societies, advocacy organizations, women’s health groups, and disease-specific foundations. In some cases, the organization specifically focuses on ovarian cancer and ovarian cancer research. However, many others focus on cancer or women’s health broadly (e.g., the American Cancer Society and the American Congress of Obstetricians and Gynecologists). Overall, private funders of ovarian cancer research tend to focus funding on biology and treatment, with very little funding directed toward the etiology of ovarian cancer or survivorship issues.

Private stakeholders can support young researchers with grant funding; provide training and educational opportunities; encourage collabora-

10 Personal communication, Patricia Modrow, data assembled by the U.S. Department of Defense Ovarian Cancer Research Program, January 16, 2015.

11 For more information about the OCS, see http://cancercontrol.cancer.gov/ocs (accessed May 15, 2015).

FIGURE 1-14 Areas of ovarian cancer research funded by the NCI. SOURCE: NCI, 2013.

tive, transdisciplinary efforts; and engage consumers, survivors, and their families. Examples of previous and current efforts by individual private stakeholders include

The Health, Empowerment, Research, and Awareness Women’s Cancer Foundation awarded the Sean Patrick Multidisciplinary Collaborative Grant for cross-disciplinary projects to allow scientists to come together and test ideas that may not be fundable by other agencies (HERA, 2015).
The Marsha Rivkin Center for Ovarian Cancer Research awards Bridge Funding Awards to researchers who are close to fundable grant scores for the DoD or the NIH but require additional data to ensure a successful resubmission (Rivkin Center, 2015).
The Ovarian Cancer Research Fund (OCRF) provides funding to researchers at all stages of their careers; OCRF awards include funding for recent graduates, newly independent researchers who are building laboratories, and senior researchers working on collaborative projects (OCRF, 2015).

FIGURE 1-15 Expertise areas for cancer survivorship research at the NCI. SOURCE: NCI, 2015c.

The Society of Gynecologic Oncology (SGO) released Pathways to Progress in Women’s Cancer in 2011, a research agenda based on discussions of working groups at a 2010 research summit. One working group focused on ovarian cancers, and the report provides short-term, intermediate, and long-term research priorities (SGO, 2011).
The Honorable Tina Brozman Foundation for Ovarian Cancer Research (also known as Tina’s Wish) funds research specifically in the early detection and prevention of ovarian cancer and also supports a consortium to advance such research (Tina’s Wish, 2015).

The Role of Advocacy in Ovarian Cancer Research

Advocacy has positively affected ovarian cancer research, public knowledge, and awareness. Many different types of people play the role of

advocate—women with ovarian cancer, partners, family members, health care professionals, and activists—and their advocacy efforts range from the individual, patient level to the societal level, but all of these different efforts have had effects on funding efforts, policy change, and the direction of research.

Patients self-advocate by taking active roles in their own care. Researchers have recognized this concept of self-advocacy as an important part of patient-centered care, and it has been described as “a distinct type of advocacy in which an individual or group supports and defends their interests either in the face of a threat or proactively to meet their needs” (Hagan and Donovan, 2013, p. 3). However, despite claims that self-advocacy may improve quality of life, health care use, and symptom management, these potential effects have not been adequately studied.

Nurses can serve as advocates for patients by protecting patients’ rights, incorporating patients’ beliefs and values into their care plans, and respecting the autonomy of the patient to ensure access to quality care (Temple, 2002). Advocacy groups provide education, information, and personal support to patients, family caregivers, and the general public. Many advocacy groups also use lobbying efforts to influence policy, including the direction of research and funding.

Large-scale advocacy efforts have arguably had a great impact on cancer research and funding. In the late 1990s, survivors advocated for wider recognition of early-stage ovarian cancer symptoms. Until that time, physicians and medical textbooks had claimed that women did not experience symptoms until advanced stages of disease (Twombly, 2007). Johanna’s Law is considered a victory of advocacy groups’ lobbying efforts. Furthermore, Congress has appropriated funds for ovarian cancer research and education programs since FY 1997. The establishment and unified efforts of national advocacy organizations are partially responsible for the significant funding increases in the intervening years (Temple, 2002).

Advocacy groups have also been integral to the advancement of ovarian cancer research through their participation in the design and administration of studies (Armstrong et al., 2014; Holman et al., 2014). The scientific literature emphasizes the importance of patient advocates in patient-centered research, citing examples of the collaboration between researchers and patient advocates in research studies (Armstrong et al., 2014; Holman et al., 2014; Staton et al., 2008).

Several large advocacy groups at the national and international levels focus on ovarian cancer. For example, the Ovarian Cancer National Alliance (OCNA), a national advocacy organization, has among its activities the Survivors Teaching Students: Saving Women’s Lives® program, which is aimed at educating caregivers and medical, nursing, and other professional

students about the early signs and symptoms of ovarian cancer. Recently, OCNA spearheaded the formation of the first congressional Ovarian Cancer Caucus with the support of Rosa DeLauro (D-CT) and Sean Duffy (R-WI). The first meeting was held on September 29, 2015, in Washington, DC. The National Ovarian Cancer Coalition (NOCC), another national advocacy organization, funds the Teal Initiative to improve education and awareness. NOCC also supports specific research in ovarian cancer and provides survivor support, primarily through its Faces of Hope program, which is “dedicated to improving the quality of life for women affected by ovarian cancer, as well as providing support for their loved ones and caregivers” (NOCC, 2014). At the international level, the charity Ovarian Cancer Action encourages collaboration among ovarian cancer researchers around the world. Half of its funds go to the Ovarian Cancer Action Research Centre in the United Kingdom, which exclusively supports “research that can be translated into meaningful outcomes for real women in real life” (Ovarian Cancer Action, 2015). In addition, every few years Ovarian Cancer Action hosts an international forum to bring researchers together to share information, inspire collaboration, and develop white papers. In 2011 the forum developed the paper Rethinking Ovarian Cancer: Recommendations for Improving Outcomes, which outlined recommendations for improving outcomes for women with ovarian cancer (Vaughan et al., 2011). A number of other advocacy groups work at the local and national levels to support research in ovarian cancer.

The Role of Consortia and Collaboration in Ovarian Cancer Research

Because of the relative rarity of ovarian cancers, especially when subdivided according to subtypes, collaborative research efforts are necessary in order to collect sufficient data for statistically significant results. Many consortia and multisite studies have evolved to promote the sharing of biospecimens, clinical data, and epidemiologic data in order to ensure sufficient sample sizes in studies. These consortia and collaborations operate at both the national and international levels. Common uses of consortia include carrying out research on the genetic and nongenetic risk factors of developing ovarian cancers, studying mechanisms of disease relapse and resistance, and identifying newer therapies (AOCS, 2015; COGS, 2009; NRG Oncology, 2015; OCAC, 2015; OCTIPS, 2015). Furthermore, groups will often team together in coalitions to promote transdisciplinary research and also to promote the translation and dissemination of information. For example, in 2015, OCNA, NOCC, and OCRF provided funding for the Stand Up To Cancer (SU2C) Dream Team for ovarian cancer. This team will bring together experts in DNA repair, translational investigators, and

clinicians “to create new programs in discovery, translation, and clinical application, while cross-fertilizing and educating researchers at all levels to enhance collaboration and catalyze translational science” (SU2C, 2015).

Consortia and coalitions have had clear, measureable impacts on the research base for ovarian cancers. For example, as a result of the Collaborative Oncological Gene-environment Study (COGS), 14 new markers for risk of ovarian cancer were identified (only 8 had been known before COGS) (COGS, 2014). Based on the work of this coalition, TCGA researchers completed a detailed analysis of ovarian cancer, which confirmed that mutations in the TP53 gene (which encodes a protein that normally suppresses tumor development) are present in nearly all HGSCs (Bell et al., 2011). The analysis also examined gene expression patterns and identified signatures that correlate with survival outcomes, affirmed four subtypes of HGSCs, and identified dozens of genes that might be targeted by gene therapy (NIH, 2011, 2015b).

NCI’s National Clinical Trials Network

In 1955 the NCI established the Clinical Trials Cooperative Group Program. As the science of cancer treatment was evolving, researchers realized that collaborative efforts were necessary to accrue sufficient numbers for clinical trials in order to more rapidly compare the value of new therapies to existing standards of care, particularly for the use of chemotherapy in the treatment of solid tumors (DiSaia et al., 2006; IOM, 2010b). The work of the cooperative groups led to advances in the treatment of women with ovarian cancer specifically, including a demonstration of the value of adding paclitaxel to cisplatin, confirmation of the value of cytoreductive surgery, and a demonstration of the value of carboplatin for late-stage ovarian cancers (IOM, 2010b). The groups have also studied issues related to the quality of life and the prevention of ovarian cancer. Between 1970 and 2005, clinical trials of the Gynecologic Oncology Group (GOG) alone included approximately 35,000 women with ovarian cancer (DiSaia et al., 2006).

In 2014, based in part on the IOM report A National Cancer Clinical Trials System for the 21st Century , the NCI transformed the cooperative group program into the new National Clinical Trials Network (IOM, 2010b, 2011, 2013b; NCI, 2015f). This reorganization consolidated nine cooperative groups into five new groups:

The Alliance for Clinical Trials in Oncology;
The ECOG-ACRIN Cancer Research Group (a merger of two cooperative groups: the Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network);
NRG Oncology (a merger of three cooperative groups: the National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the GOG);
The Southwest Oncology Group; and
The Children’s Oncology Group (NCI, 2015f).

PREVIOUS WORK AT THE INSTITUTE OF MEDICINE

The IOM has a long history of producing reports related to various aspects of cancer care, and many of them are directly relevant to this current study. This section describes some examples of previous IOM work that is related to the work of this committee.

Prevention and Early Detection

In 2005 the IOM report Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis (IOM, 2005) recommended the development of tools to identify the women who would benefit most from breast cancer screening based on “individually tailored risk prediction techniques that integrate biologic and other risk factors.” The report also called for the development of tools that “facilitate communication regarding breast cancer risk to the public and to health care providers.” In addition, the report called for more research on breast cancer screening and detection technologies, including research on various aspects of technology adoption (e.g., monitoring the use of technology in clinical practice).

A 2007 IOM report, Cancer Biomarkers , offered recommendations on the methods, tools, and resources needed to discover and develop biomarkers for cancer; guidelines, standards, oversight, and incentives needed for biomarker development; and the methods and processes needed for clinical evaluation and adoption of such biomarkers (IOM, 2007a). Specific recommendations from the report included establishing international consortia to generate and share data, supporting high-quality biorepositories of prospectively collected samples, and developing criteria for conditional coverage of new biomarker tests. Subsequently, in 2010, an IOM report, Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease , outlined a framework for the evaluation of biomarkers (IOM, 2010a).

In Initial National Priorities for Comparative Effectiveness Research (IOM, 2009), the committee offered two priorities that are relevant to ovarian cancer genetics: “Compare the effectiveness of adding informa-

tion about new biomarkers (including genetic information) with standard care in motivating behavior change and improving clinical outcomes” and “Compare the effectiveness of genetic and biomarker testing and usual care in preventing and treating breast, colorectal, prostate, lung, and ovarian cancer, and possibly other clinical conditions for which promising biomarkers exist” (IOM, 2009, p. 4).

In 2007, the IOM’s National Cancer Policy Forum hosted a workshop on cancer-related genetic testing and counseling. According to the published summary of that workshop, participants observed that “genetic testing and counseling are becoming more complex and important for informing patients and families of risks and benefits of certain courses of action, and yet organized expert programs are in short supply. The subject matter involves not only the scientific and clinical aspects but also workforce and reimbursement issues, among others” (IOM, 2007b)

Clinical Trials

The 2005 IOM report on breast cancer detection called for public health campaigns and for improved information and communication about the value of participation in clinical trials (including the participation of healthy individuals).

A 2010 report, A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program (IOM, 2010b), called for the restructuring of the NCI Cooperative Group Program and set four goals:

Improve the speed and efficiency of the design, launch, and conduct of clinical trials (e.g., improve collaboration among stakeholders);
Incorporate innovative science and trial design into cancer clinical trials (e.g., support standardized central biorepositories, develop and evaluate novel trial designs);
Improve the means of prioritization, selection, support, and completion of cancer clinical trials (e.g., develop national unified standards); and
Incentivize the participation of patients and physicians in clinical trials (e.g., develop electronic tools to alert clinicians to available trials for specific patients, encourage eligibility criteria to allow broad participation, cover cost of patient care in trials).

Palliative and End-of-Life Care

Improving Palliative Care for Cancer (IOM, 2001) called for incorporating palliative care into clinical trials. The report also noted that infor-

mation on palliative and end-of-life care is largely absent from materials developed for the public about cancer treatment, and the committee recommended strategies for disseminating information and improving education about end-of-life care. The report recommended that the NCI require comprehensive cancer centers to carry out research in palliative care and symptom control and that the Health Care Finance Administration (now the Centers for Medicare & Medicaid Services) fund demonstration projects for service delivery and reimbursement that integrate palliative care throughout the course of the disease.

Dying in America (IOM, 2015) noted that palliative care can begin early in the course of treatment, in conjunction with treatment, and can continue throughout the continuum of care. The report further observed that “a palliative approach can offer patients near the end of life and their families the best chance of maintaining the highest possible quality of life for the longest possible time” (IOM, 2015, p. 1).

Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis (IOM, 2013a) addressed the delivery of cancer care, including palliative and end-of-life care. The study called for providing patients and their families with understandable information about palliative (and other) care and recommended that “the cancer care team should provide patients with end-of-life care consistent with their needs, values, and preferences” (IOM, 2013a, p. 9).

Communication and Survivorship

From Cancer Patient to Cancer Survivor (IOM, 2006) called for actions to raise awareness about the needs of cancer survivors, including the establishment of cancer survivorship as a distinct phase of cancer care. In 2008, the IOM report Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs (IOM, 2008) recommended that facilitating effective communication between patients and care providers, identifying psychosocial health needs, and engaging and supporting patients in managing their illnesses should all be considered as part of the standard of care. The report emphasized the importance of educating patients and their families and of enabling patients to actively participate in their own care by providing tools and training in how to obtain information, make decisions, solve problems, and communicate more effectively with their health care providers. The report further called for the government to invest in a large-scale demonstration and evaluation of various approaches to the efficient provision of psychosocial health care.

Women’s Health Research (IOM, 2010c) found that there are many barriers to the translation of research findings in general and that some have aspects that are “peculiar to women.” The committee recommended

specific research on how to translate research findings on women’s health into clinical practice and public health policies.

Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis (IOM, 2013a) called for providing patients and their families with “understandable information on cancer prognosis, treatment benefits and harms, palliative care, psychosocial support, and estimates of the total and out-of-pocket costs of cancer care.” The report further called for the development of decision aids to be made available through print, electronic, and social media; for the formal training of cancer care team members in communication; for the communication of relevant and personalized information at key decision points along the continuum of cancer care; and for consideration of patients’ individual needs, values, and preferences when developing a care plan, including end-of-life care. The report also called for the identification and public dissemination of evidence-based information about cancer care practices that are unnecessary or for which the harm may outweigh the benefits.

OVERVIEW OF THE REPORT

This chapter has provided an overview of the study charge and the committee’s approach to its work. It has also provided an introduction to the challenges in ovarian cancer research, to defining and classifying ovarian cancers, to the patterns and demographics of the disease, and to the landscape of stakeholders in ovarian cancer research. The remaining chapters follow the research framework outlined in Figure 1-1 .

Chapter 2 describes the current state of the science in the biology of ovarian cancers, thus providing a foundation for the descriptions of most of the other ovarian cancer research covered in this report. This background includes information about the characteristics of specific ovarian carcinomas, the role of the tumor microenvironment, and experimental model systems.

Chapter 3 builds on this to discuss research on the prevention and early detection of ovarian cancers. On the topic of risk assessment, the chapter includes discussions of a wide range of genetic and nongenetic risk factors for the development of an ovarian cancer, risk-prediction models, and genetic testing. Concerning prevention, both surgical and nonsurgical prevention strategies are discussed. And on the topic of early detection, the chapter has descriptions of various approaches to identifying ovarian cancers earlier, including biomarkers and imaging techniques, and a discussion of the challenges in performing screening in both general and high-risk populations.

Chapter 4 describes the research base for the diagnosis and treatment of women newly diagnosed with ovarian cancer as well as for women with

relapsed ovarian cancer. The chapter outlines research on current standards of care and also explores the development of novel therapeutics such as anti-angiogenics, poly ADP ribose polymerase (PARP) inhibitors, and immunotherapy. Later, the chapter discusses issues of clinical trial development and use as they relate specifically to research in ovarian cancer.

Chapter 5 discusses research on survivorship and management issues along the entire care continuum from diagnosis to end of life. Furthermore, women who are at a high risk for developing cancer (sometimes referred to as “previvors”) may have psychosocial needs of their own that should be studied. Overall, research that focuses specifically on survivorship and management issues in ovarian cancer is scarce; it may thus be necessary to apply research from broader studies of survivorship to women with ovarian cancer. The chapter discusses the research base for the unique issues of survivorship and management for women with ovarian cancer and their families, including managing the physical side effects of treatment, addressing unique psychosocial impacts, engaging women in their own self-care, and addressing end-of-life concerns.

Chapter 6 summarizes the findings and conclusions of the previous chapters in order to provide a cohesive set of recommendations for prioritizing research on ovarian cancers in such a way as to have the greatest impact on reducing morbidity and mortality from the disease.

Chapter 7 gives an overview of research on the translation and dissemination of new information to the general public, providers, researchers, policy makers, and others. The chapter reflects on the messages within the previous chapters that are ready to be communicated and identifies potential avenues for communicating these messages.

Finally, the report contains five appendixes. Appendix A contains a list of key acronyms used throughout the report. Appendix B contains a glossary of key terms. Appendix C includes a listing of currently active studies on epithelial ovarian cancer (based on information available through www.ClinicalTrials.gov ) in order to give a sense of where emphasis is being placed in future research. Appendix D lists the agendas of the committee’s workshops. Appendix E contains the biographical sketches of the committee members and project staff.

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SU2C (Stand Up To Cancer). 2015. SU2C-ovarian cancer research fund-ovarian cancer national alliance-national ovarian cancer coalition dream team: DNA repair therapies for ovarian cancer. https://www.standup2cancer.org/dream_teams/view/su2c_ocrf_ocna_nocc_ovarian_cancer_dream_team (accessed September 21, 2015).

Temple, S. V. 2002. The advocacy movement in gynecologic oncology. Seminars in Oncology Nursing 18(3):231-235.

Tina’s Wish. 2015. About Tina’s Wish. http://www.tinabrozmanfoundation.org/about-tinas-wish (accessed October 22, 2015).

Twombly, R. 2007. Cancer killer may be “silent” no more. Journal of the National Cancer Institute 99(18):1359-1361.

Vaughan, S., J. I. Coward, R. C. Bast, Jr., A. Berchuck, J. S. Berek, et al. 2011. Rethinking ovarian cancer: Recommendations for improving outcomes. Nature Reviews: Cancer 11(10):719-725.

In an era of promising advances in cancer research, there are considerable and even alarming gaps in the fundamental knowledge and understanding of ovarian cancer. Researchers now know that ovarian cancer is not a single disease—several distinct subtypes exist with different origins, risk factors, genetic mutations, biological behaviors, and prognoses. However, persistent questions have impeded progress toward improving the prevention, early detection, treatment, and management of ovarian cancers. Failure to significantly improve morbidity and mortality during the past several decades is likely due to several factors, including the lack of research being performed by specific disease subtype, lack of definitive knowledge of the cell of origin and disease progression, and incomplete understanding of genetic and non-genetic risk factors.

Ovarian Cancers examines the state of the science in ovarian cancer research, identifies key gaps in the evidence base and the challenges to addressing those gaps, considers opportunities for advancing ovarian cancer research, and examines avenues for translation and dissemination of new findings and communication of new information to patients and others. This study makes recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of morbidity and mortality from ovarian cancers.

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Health Thesis Topics

450 Health Thesis Topics and Ideas

Health sciences are an ever-evolving field, with new discoveries, innovations, and challenges shaping healthcare practices, medical research, and public health policies. As health issues become more complex and globalized, students pursuing degrees in health-related fields must select thesis topics that reflect both current challenges and future trends. This comprehensive list of 450 health thesis topics is divided into 15 categories, providing a broad range of subjects for students to explore. Whether you’re focusing on clinical medicine, public health, or specialized fields such as nursing or occupational therapy, these topics offer ample opportunities for meaningful and impactful research.

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Get 10% off with 24start discount code, 1. anatomy thesis topics.

The impact of aging on muscle mass and function.
Investigating the anatomical variations in the human liver.
The role of the lymphatic system in cancer metastasis.
Exploring the anatomy of the human brain in neurodegenerative diseases.
Anatomical changes in the cardiovascular system due to hypertension.
Investigating the structural changes in bones with osteoporosis.
The anatomy of the respiratory system in patients with chronic obstructive pulmonary disease (COPD).
Exploring the anatomical adaptations in athletes’ muscles.
The role of anatomical studies in improving surgical outcomes.
Investigating the relationship between body fat distribution and metabolic disorders.
The anatomy of the gastrointestinal tract in patients with inflammatory bowel disease.
Anatomical differences in male and female pelvic structures.
Investigating the development of the fetal brain during pregnancy.
The anatomy of the immune system in autoimmune diseases.
Exploring the role of anatomical variations in cardiovascular diseases.
Investigating the impact of obesity on musculoskeletal anatomy.
The anatomical basis of joint pain in arthritis.
Exploring the relationship between spinal anatomy and chronic back pain.
The role of anatomical studies in improving robotic surgery techniques.
Anatomical changes in the brain due to traumatic brain injury.
Investigating the anatomy of the heart in congenital heart diseases.
Exploring the anatomical structure of the skin in patients with eczema.
The anatomy of the reproductive system in patients with infertility.
Investigating the anatomical basis of sleep apnea.
Exploring the role of the diaphragm in respiratory disorders.
Anatomical changes in the aging brain and their impact on cognitive decline.
Investigating the structure of blood vessels in patients with diabetes.
The role of anatomical studies in forensic medicine.
Exploring the anatomy of the ear in patients with hearing loss.
Investigating the anatomical differences in patients with scoliosis.

2. Epidemiology Thesis Topics

Investigating the epidemiology of COVID-19 in urban and rural areas.
The impact of vaccination programs on the epidemiology of measles.
Exploring the relationship between socioeconomic status and the prevalence of type 2 diabetes.
Investigating the epidemiology of mental health disorders in adolescents.
The role of public health interventions in reducing the incidence of malaria.
Exploring the epidemiology of obesity in low-income communities.
Investigating the epidemiology of sexually transmitted infections among college students.
The impact of environmental factors on the epidemiology of asthma.
Exploring the role of epidemiology in controlling the spread of infectious diseases.
Investigating the epidemiology of cardiovascular diseases in aging populations.
The role of epidemiology in cancer prevention and control.
Exploring the epidemiology of substance abuse in young adults.
Investigating the role of epidemiological studies in global health initiatives.
The impact of climate change on the epidemiology of vector-borne diseases.
Investigating the epidemiology of chronic kidney disease in developing countries.
Exploring the role of epidemiology in improving maternal and child health.
The impact of dietary patterns on the epidemiology of hypertension.
Investigating the epidemiology of mental health disorders in conflict zones.
The role of epidemiology in addressing health disparities in minority populations.
Exploring the epidemiology of tuberculosis in immigrant communities.
Investigating the impact of public health policies on the epidemiology of HIV/AIDS.
The role of epidemiology in reducing the burden of non-communicable diseases.
Investigating the epidemiology of depression in older adults.
Exploring the epidemiology of childhood obesity and its long-term health effects.
The role of epidemiological data in shaping public health policy.
Investigating the epidemiology of respiratory infections in industrial workers.
The impact of socioeconomic factors on the epidemiology of chronic diseases.
Exploring the epidemiology of maternal mortality in low-income countries.
Investigating the role of epidemiology in reducing the global burden of cancer.
The role of epidemiology in preparing for future pandemics.

3. Food and Nutrition Thesis Topics

Investigating the impact of diet on gut microbiota composition.
Exploring the relationship between sugar consumption and obesity.
The role of nutrition in managing type 2 diabetes.
Investigating the nutritional needs of aging populations.
The impact of fast food consumption on childhood obesity rates.
Exploring the role of nutrition in promoting mental health.
Investigating the effects of dietary supplements on athletic performance.
The relationship between nutrition and immune system function.
Exploring the role of nutrition in cancer prevention.
Investigating the impact of food insecurity on child development.
The role of plant-based diets in reducing the risk of cardiovascular diseases.
Exploring the nutritional challenges faced by individuals with food allergies.
Investigating the role of nutrition in managing hypertension.
The impact of vegetarian and vegan diets on overall health outcomes.
Exploring the relationship between nutrition and cognitive function in older adults.
Investigating the effects of processed foods on metabolic health.
The role of nutrition education in preventing childhood obesity.
Exploring the impact of malnutrition on maternal and child health.
Investigating the role of dietary patterns in the prevention of chronic diseases.
The impact of food advertising on consumer behavior and dietary choices.
Exploring the role of nutrition in improving outcomes for cancer patients.
Investigating the effects of micronutrient deficiencies on public health.
The role of nutrition in managing gastrointestinal disorders.
Exploring the impact of dietary interventions on weight loss and maintenance.
Investigating the role of nutrition in improving bone health.
The relationship between dietary habits and the prevalence of eating disorders.
Exploring the impact of food labeling on consumer choices and health outcomes.
Investigating the role of nutrition in enhancing athletic recovery.
The effects of maternal nutrition on fetal development and birth outcomes.
Exploring the role of nutrition in reducing health disparities in vulnerable populations.

4. General Medicine Thesis Topics

Investigating the role of telemedicine in improving patient care.
The impact of antibiotic resistance on public health outcomes.
Exploring the use of personalized medicine in the treatment of cancer.
Investigating the effectiveness of vaccinations in preventing infectious diseases.
The role of primary care in managing chronic diseases.
Exploring the impact of artificial intelligence in diagnosing medical conditions.
Investigating the role of mental health services in primary care settings.
The impact of electronic health records on patient outcomes.
Exploring the role of gene therapy in treating genetic disorders.
Investigating the effects of climate change on public health.
The role of medical education in addressing healthcare disparities.
Exploring the impact of lifestyle changes on cardiovascular disease management.
Investigating the role of interdisciplinary teams in improving patient care.
The impact of healthcare policies on patient access to care.
Exploring the role of precision medicine in managing chronic diseases.
Investigating the effects of sleep deprivation on overall health.
The role of public health campaigns in promoting disease prevention.
Exploring the impact of the opioid crisis on public health.
Investigating the role of clinical trials in advancing medical research.
The impact of healthcare costs on patient decision-making.
Exploring the role of alternative medicine in managing chronic pain.
Investigating the effects of stress on physical and mental health.
The role of patient-centered care in improving healthcare outcomes.
Exploring the impact of digital health technologies on patient engagement.
Investigating the role of early detection in cancer treatment success rates.
The impact of global health initiatives on reducing infectious disease burdens.
Exploring the role of medical ethics in patient care decisions.
Investigating the effects of alcohol consumption on long-term health outcomes.
The role of public health surveillance in detecting disease outbreaks.
Exploring the impact of mental health awareness campaigns on reducing stigma.

5. Gynecology Thesis Topics

Investigating the effects of hormonal contraceptives on reproductive health.
Exploring the role of gynecological screening in detecting cervical cancer.
The impact of polycystic ovary syndrome (PCOS) on fertility.
Investigating the relationship between endometriosis and chronic pain.
The role of nutrition in managing menopause symptoms.
Exploring the effectiveness of fertility treatments in women with PCOS.
Investigating the role of early detection in preventing ovarian cancer.
The impact of lifestyle factors on reproductive health in women.
Exploring the role of hormonal therapies in managing endometriosis.
Investigating the effects of pregnancy on cardiovascular health.
The role of gynecological surgery in treating uterine fibroids.
Exploring the impact of pelvic inflammatory disease on reproductive outcomes.
Investigating the relationship between obesity and infertility in women.
The role of exercise in managing pregnancy-related complications.
Exploring the effects of prenatal care on maternal and fetal health.
Investigating the impact of age on fertility and pregnancy outcomes.
The role of family planning services in improving reproductive health outcomes.
Exploring the relationship between mental health and reproductive health in women.
Investigating the effects of childbirth on pelvic floor function.
The impact of gynecological cancers on women’s health and quality of life.
Exploring the role of assisted reproductive technologies in treating infertility.
Investigating the effects of menstrual disorders on women’s mental health.
The role of hormone replacement therapy in managing menopause symptoms.
Exploring the relationship between autoimmune diseases and reproductive health.
Investigating the impact of gynecological surgeries on long-term health outcomes.
The role of genetic testing in predicting gynecological cancer risk.
Exploring the impact of reproductive health education on adolescent health outcomes.
Investigating the effects of environmental toxins on reproductive health.
The role of midwifery in improving maternal health outcomes.
Exploring the impact of stress on reproductive health and fertility.

6. Healthcare Thesis Topics

Investigating the impact of healthcare access on patient outcomes in rural areas.
The role of telemedicine in improving healthcare delivery in underserved regions.
Exploring the effectiveness of healthcare policies in addressing health disparities.
Investigating the impact of healthcare workforce shortages on patient care.
The role of electronic health records in improving patient safety and healthcare efficiency.
Exploring the influence of healthcare leadership on organizational performance.
Investigating the effectiveness of public health campaigns in reducing preventable diseases.
The role of health insurance in improving access to healthcare services.
Exploring the effects of healthcare reforms on patient access and care quality.
Investigating the impact of healthcare costs on patients’ health-seeking behaviors.
The role of patient-centered care in improving chronic disease management.
Exploring the influence of healthcare provider communication on patient satisfaction.
Investigating the effects of healthcare technology on patient safety and outcomes.
The role of healthcare management in reducing medical errors.
Exploring the impact of patient advocacy programs on healthcare quality.
Investigating the role of healthcare policy in addressing mental health issues.
The impact of value-based care on healthcare delivery and outcomes.
Exploring the role of healthcare financing in improving health equity.
Investigating the effects of hospital staffing ratios on patient outcomes.
The role of healthcare providers in promoting preventive care.
Exploring the impact of healthcare marketing on patient decision-making.
Investigating the role of public-private partnerships in healthcare delivery.
The impact of healthcare delivery models on patient access to care.
Exploring the role of healthcare quality improvement initiatives in enhancing patient care.
Investigating the impact of healthcare regulations on provider practices.
The role of healthcare informatics in improving clinical decision-making.
Exploring the effects of healthcare mergers and acquisitions on patient outcomes.
Investigating the role of healthcare systems in responding to public health emergencies.
The impact of mental health services integration into primary care on patient outcomes.
Exploring the effects of global health initiatives on healthcare delivery in developing countries.

7. Histopathology Thesis Topics

Investigating the role of histopathology in diagnosing cancer.
The impact of molecular techniques on histopathological analysis.
Exploring the relationship between histopathological findings and patient prognosis in breast cancer.
Investigating the role of histopathology in detecting autoimmune diseases.
The impact of histopathology on early detection of colorectal cancer.
Exploring the role of biopsy techniques in histopathological analysis.
Investigating the role of immunohistochemistry in diagnosing infectious diseases.
The impact of digital pathology on the accuracy and speed of histopathological diagnoses.
Exploring the use of histopathology in forensic investigations.
Investigating the role of histopathology in diagnosing rare genetic disorders.
The relationship between histopathological findings and patient outcomes in lung cancer.
Exploring the role of histopathology in understanding neurodegenerative diseases.
Investigating the effects of tissue preservation techniques on histopathological analysis.
The role of histopathology in diagnosing inflammatory bowel disease.
Exploring the use of histopathology in liver disease diagnosis and management.
Investigating the role of histopathology in detecting skin cancers.
The impact of histopathological grading on cancer treatment decisions.
Exploring the role of histopathology in diagnosing kidney disease.
Investigating the effects of histological staining techniques on diagnostic accuracy.
The role of histopathology in detecting and diagnosing cardiovascular diseases.
Exploring the relationship between histopathology and precision medicine in oncology.
Investigating the use of histopathology in understanding tissue regeneration processes.
The impact of machine learning on histopathological image analysis.
Exploring the role of histopathology in identifying treatment-resistant cancer cells.
Investigating the role of histopathology in assessing the effects of novel cancer therapies.
The relationship between histopathology and personalized treatment plans in cancer care.
Exploring the use of histopathology in diagnosing neurological tumors.
Investigating the role of histopathology in detecting early signs of liver fibrosis.
The role of histopathology in understanding chronic inflammatory diseases.
Exploring the impact of telepathology on histopathological diagnostic services.

8. ICU (Intensive Care Unit) Thesis Topics

Investigating the role of ICU care in improving outcomes for patients with sepsis.
The impact of nurse-to-patient ratios in the ICU on patient survival rates.
Exploring the effects of family presence during ICU care on patient outcomes.
Investigating the role of ICU protocols in reducing hospital-acquired infections.
The role of mechanical ventilation in improving outcomes for patients with respiratory failure.
Exploring the impact of early mobilization programs in the ICU on recovery times.
Investigating the effects of sedation protocols on patient outcomes in the ICU.
The role of ICU care in managing patients with multiple organ dysfunction syndrome (MODS).
Exploring the impact of nutrition management in critically ill ICU patients.
Investigating the role of ICU care in improving outcomes for trauma patients.
The impact of palliative care integration into the ICU on patient and family satisfaction.
Exploring the role of ICU care in managing patients with acute respiratory distress syndrome (ARDS).
Investigating the effects of early goal-directed therapy on sepsis outcomes in the ICU.
The role of ICU care in preventing complications in post-surgical patients.
Exploring the impact of tele-ICU services on patient outcomes.
Investigating the role of infection control measures in the ICU in reducing antimicrobial resistance.
The impact of continuous renal replacement therapy (CRRT) in the ICU on patient outcomes.
Exploring the role of critical care ultrasonography in ICU patient management.
Investigating the effects of nurse-led ICU interventions on patient recovery.
The role of ICU care in managing patients with traumatic brain injuries.
Exploring the impact of ICU delirium on long-term cognitive outcomes.
Investigating the role of family-centered care in improving ICU outcomes.
The impact of advanced hemodynamic monitoring in ICU care on patient outcomes.
Exploring the role of ICU care in managing patients with acute kidney injury.
Investigating the effects of ICU discharge planning on post-ICU patient outcomes.
The role of ICU team communication in improving patient safety and outcomes.
Exploring the impact of early ICU interventions on patient recovery after cardiac arrest.
Investigating the role of ICU care in managing patients with severe COVID-19.
The effects of ICU care bundles on reducing ventilator-associated pneumonia.
Exploring the role of ECMO (extracorporeal membrane oxygenation) in ICU patient management.

9. Medical Thesis Topics

Investigating the role of gene therapy in treating inherited genetic disorders.
The impact of precision medicine on the treatment of cancer.
Exploring the effectiveness of immunotherapy in managing autoimmune diseases.
Investigating the role of regenerative medicine in treating musculoskeletal injuries.
The impact of medical technologies on early disease diagnosis.
Exploring the role of personalized medicine in managing cardiovascular diseases.
Investigating the use of stem cells in the treatment of neurodegenerative diseases.
The impact of robotic surgery on improving patient outcomes in minimally invasive procedures.
Exploring the role of nanomedicine in cancer therapy.
Investigating the effects of gene editing techniques on inherited disorders.
The role of biomarkers in early cancer detection and treatment.
Exploring the impact of artificial intelligence in medical diagnostics.
Investigating the role of pharmacogenomics in individualized drug therapies.
The impact of wearable medical devices on chronic disease management.
Exploring the use of virtual reality in medical training and patient rehabilitation.
Investigating the role of digital health tools in improving patient self-management.
The impact of artificial organs on organ transplantation outcomes.
Exploring the use of machine learning in predicting disease outcomes.
Investigating the role of telemedicine in improving access to healthcare services.
The impact of 3D printing in reconstructive surgery and prosthetics.
Exploring the role of CRISPR technology in treating genetic disorders.
Investigating the effects of personalized vaccines in cancer immunotherapy.
The impact of clinical decision support systems on patient safety and care quality.
Exploring the role of microbiome therapies in treating chronic inflammatory diseases.
Investigating the effects of mobile health applications on patient adherence to treatment.
The role of AI-assisted surgery in improving surgical precision and outcomes.
Exploring the impact of pharmacovigilance in reducing adverse drug reactions.
Investigating the role of digital twins in personalized healthcare.
The effects of personalized nutrition plans in managing metabolic disorders.
Exploring the role of digital therapeutics in managing mental health disorders.

10. Nursing Thesis Topics

Investigating the role of nursing leadership in improving patient care outcomes.
The impact of nurse-led interventions on managing chronic diseases.
Exploring the role of evidence-based nursing practices in enhancing patient safety.
Investigating the effects of nursing education programs on reducing burnout.
The role of nurse-patient communication in improving patient satisfaction.
Exploring the impact of nurse-led health promotion programs on community health.
Investigating the role of advanced practice nurses in primary care settings.
The impact of nursing care models on patient outcomes in acute care settings.
Exploring the role of nursing informatics in improving patient care delivery.
Investigating the effects of nursing interventions on reducing hospital readmissions.
The role of critical thinking skills in enhancing nursing practice.
Exploring the impact of culturally competent nursing care on patient satisfaction.
Investigating the role of nurse-led initiatives in improving medication adherence.
The impact of holistic nursing practices on patient well-being.
Exploring the role of mentorship in advancing nursing careers.
Investigating the effects of nurse-led discharge planning on patient outcomes.
The role of nursing interventions in preventing pressure ulcers.
Exploring the impact of nurse-led education programs on patient self-care management.
Investigating the role of nursing in managing patients with chronic pain.
The impact of nurse-patient ratios on patient safety and quality of care.
Exploring the role of nursing in palliative care and end-of-life decision-making.
Investigating the effects of nurse-led wound care management on patient recovery.
The role of nursing in managing patients with diabetes.
Exploring the impact of nursing research on improving patient care outcomes.
Investigating the role of nurse-led mental health interventions in reducing anxiety and depression.
The impact of nursing advocacy on improving healthcare policies.
Exploring the role of nursing in promoting patient autonomy in decision-making.
Investigating the effects of nurse-led smoking cessation programs on long-term outcomes.
The role of nursing in managing patients with heart failure.
Exploring the impact of nursing leadership on promoting a culture of safety in healthcare.

11. Nutrition Thesis Topics

Investigating the role of micronutrients in preventing chronic diseases.
The impact of plant-based diets on cardiovascular health.
Exploring the relationship between diet and mental health outcomes.
Investigating the role of nutritional education in combating childhood obesity.
The effects of intermittent fasting on metabolic health.
Exploring the impact of nutrition on athletic performance and recovery.
Investigating the role of probiotics in improving gut health.
The impact of maternal nutrition on fetal development and birth outcomes.
Exploring the effects of high-protein diets on weight loss and muscle mass.
Investigating the role of omega-3 fatty acids in reducing inflammation.
The relationship between ultra-processed foods and metabolic disorders.
Exploring the impact of cultural dietary patterns on health outcomes.
Investigating the role of vitamins and minerals in immune system function.
The effects of ketogenic diets on weight loss and metabolic health.
Exploring the role of nutrition in managing autoimmune diseases.
Investigating the relationship between diet and the development of type 2 diabetes.
The impact of sugar consumption on public health and chronic disease.
Exploring the role of nutritional interventions in reducing hypertension.
Investigating the effects of food marketing on dietary habits in children and adolescents.
The relationship between alcohol consumption and nutritional deficiencies.
Exploring the role of dietary fiber in preventing gastrointestinal diseases.
Investigating the impact of meal timing on weight management and metabolic health.
The role of nutritional support in cancer treatment and recovery.
Exploring the relationship between diet and sleep quality.
Investigating the impact of food security on nutrition in low-income populations.
The role of personalized nutrition in managing chronic diseases.
Exploring the effects of artificial sweeteners on metabolic health.
Investigating the role of nutrition in bone health and osteoporosis prevention.
The relationship between diet diversity and overall health outcomes.
Exploring the impact of food allergies and intolerances on nutrition and health.

12. Obstetrics and Gynaecology Thesis Topics

Investigating the role of prenatal care in reducing maternal mortality rates.
The impact of maternal age on pregnancy outcomes.
Exploring the role of hormonal therapy in treating polycystic ovary syndrome (PCOS).
Investigating the effects of gestational diabetes on maternal and fetal health.
The role of early prenatal diagnosis in managing congenital abnormalities.
Exploring the impact of cesarean sections on long-term maternal health.
Investigating the relationship between maternal nutrition and pregnancy outcomes.
The role of assisted reproductive technologies in treating infertility.
Exploring the effects of preeclampsia on maternal and fetal outcomes.
Investigating the impact of endometriosis on fertility and reproductive health.
The role of prenatal screening in reducing birth defects.
Exploring the effects of pregnancy complications on mental health.
Investigating the relationship between maternal obesity and pregnancy complications.
The role of antenatal education in improving pregnancy outcomes.
Exploring the impact of postpartum depression on maternal and infant health.
Investigating the effects of multiple pregnancies on maternal health.
The role of breastfeeding in promoting maternal and infant health.
Exploring the impact of pelvic floor disorders on women’s reproductive health.
Investigating the relationship between smoking during pregnancy and fetal development.
The role of gynecological cancers in women’s overall health and fertility.
Exploring the effects of intrauterine growth restriction on neonatal outcomes.
Investigating the impact of delayed childbirth on maternal health.
The role of prenatal care in preventing premature births.
Exploring the relationship between maternal mental health and pregnancy outcomes.
Investigating the impact of HIV on pregnancy and childbirth outcomes.
The role of maternal stress on fetal development and birth outcomes.
Exploring the effects of childbirth interventions on maternal health.
Investigating the role of genetic counseling in managing inherited reproductive conditions.
The relationship between maternal sleep patterns and pregnancy outcomes.
Exploring the impact of assisted reproduction on maternal health and pregnancy outcomes.

13. Occupational Therapy Thesis Topics

Investigating the role of occupational therapy in improving the quality of life for stroke patients.
The impact of early intervention occupational therapy on children with developmental delays.
Exploring the role of occupational therapy in managing chronic pain.
Investigating the effectiveness of occupational therapy in rehabilitation after traumatic brain injury.
The role of occupational therapy in enhancing motor skills in children with autism spectrum disorder.
Exploring the impact of occupational therapy in managing mental health disorders.
Investigating the role of occupational therapy in promoting independence in older adults.
The impact of sensory integration therapy in children with sensory processing disorders.
Exploring the role of occupational therapy in improving functional abilities after spinal cord injuries.
Investigating the effectiveness of hand therapy in occupational rehabilitation.
The role of occupational therapy in managing patients with multiple sclerosis.
Exploring the impact of home-based occupational therapy on patient outcomes.
Investigating the effects of occupational therapy on cognitive rehabilitation.
The role of occupational therapy in managing patients with degenerative neurological conditions.
Exploring the impact of occupational therapy in improving the quality of life for cancer patients.
Investigating the role of occupational therapy in work-related injury rehabilitation.
The effectiveness of virtual reality in occupational therapy interventions.
Exploring the role of occupational therapy in managing patients with Alzheimer’s disease.
Investigating the impact of occupational therapy on mental health in the workplace.
The role of occupational therapy in improving fine motor skills after surgery.
Exploring the effects of occupational therapy on improving activities of daily living in stroke survivors.
Investigating the impact of group-based occupational therapy on social skills development.
The role of occupational therapy in managing chronic fatigue syndrome.
Exploring the impact of assistive technology on occupational therapy outcomes.
Investigating the effectiveness of community-based occupational therapy programs.
The role of occupational therapy in managing anxiety and depression in adolescents.
Exploring the effects of occupational therapy on improving cognitive functions in dementia patients.
Investigating the role of occupational therapy in supporting children with learning disabilities.
The impact of occupational therapy in improving life skills in individuals with intellectual disabilities.
Exploring the role of occupational therapy in managing musculoskeletal disorders.

14. Physiology Thesis Topics

Investigating the role of the autonomic nervous system in regulating cardiovascular function.
The impact of exercise on muscle physiology and performance.
Exploring the role of hormones in regulating metabolism and body weight.
Investigating the effects of stress on the endocrine system.
The role of physiological changes in aging and their impact on health.
Exploring the relationship between circadian rhythms and sleep physiology.
Investigating the role of the respiratory system in maintaining acid-base balance.
The impact of dehydration on kidney function and electrolyte balance.
Exploring the effects of chronic inflammation on tissue physiology.
Investigating the role of exercise on improving cardiac function in patients with heart disease.
The effects of altitude on oxygen transport and muscle function.
Exploring the physiological adaptations to endurance training.
Investigating the role of the immune system in inflammation and tissue repair.
The impact of diet on metabolic regulation and energy balance.
Exploring the physiological mechanisms underlying thermoregulation.
Investigating the effects of aging on cognitive function and brain physiology.
The role of physiological changes during pregnancy in fetal development.
Exploring the relationship between blood pressure regulation and kidney function.
Investigating the role of neurotransmitters in mood regulation and mental health.
The impact of physical activity on glucose metabolism in type 2 diabetes.
Exploring the effects of chronic stress on cardiovascular physiology.
Investigating the physiological mechanisms of muscle hypertrophy and strength gain.
The role of inflammation in the development of cardiovascular diseases.
Exploring the effects of sleep deprivation on metabolic physiology.
Investigating the physiological responses to extreme temperatures in athletes.
The role of vascular physiology in hypertension and heart disease.
Exploring the physiological mechanisms of fatigue during prolonged exercise.
Investigating the effects of intermittent fasting on metabolic function.
The role of respiratory physiology in managing chronic respiratory diseases.
Exploring the physiological basis of exercise-induced muscle damage and recovery.

15. Public Health Thesis Topics

Investigating the impact of vaccination programs on public health outcomes.
The role of public health campaigns in reducing the prevalence of smoking.
Exploring the effectiveness of public health policies in addressing obesity.
Investigating the role of sanitation programs in improving public health in developing countries.
The impact of environmental factors on public health and disease prevention.
Exploring the relationship between public health education and the prevention of chronic diseases.
Investigating the role of community health workers in promoting public health initiatives.
The effectiveness of public health interventions in reducing the spread of infectious diseases.
Exploring the role of public health surveillance in detecting disease outbreaks.
Investigating the impact of public health nutrition programs on reducing childhood obesity.
The role of public health strategies in managing mental health crises.
Exploring the relationship between urban planning and public health outcomes.
Investigating the role of public health initiatives in promoting reproductive health.
The impact of clean water initiatives on public health in rural areas.
Exploring the effectiveness of public health campaigns in increasing vaccination rates.
Investigating the role of public health policies in addressing substance abuse.
The impact of climate change on public health and disease patterns.
Exploring the role of public health in managing aging populations.
Investigating the effects of health disparities on public health outcomes.
The role of public health initiatives in improving maternal and child health.
Exploring the impact of public health interventions on reducing health disparities in minority populations.
Investigating the effectiveness of public health programs in managing infectious diseases in refugee camps.
The role of public health education in promoting healthy behaviors in school-aged children.
Exploring the relationship between socioeconomic factors and public health outcomes.
Investigating the role of public health organizations in combating the opioid epidemic.
The impact of air pollution on public health and respiratory diseases.
Exploring the role of public health policies in addressing global health crises.
Investigating the effectiveness of public health strategies in reducing healthcare costs.
The role of public health in preventing and managing non-communicable diseases.
Exploring the impact of public health leadership in promoting community wellness initiatives.

This comprehensive list of 450 health thesis topics spans a wide range of disciplines within the field of health sciences, offering students diverse opportunities for research. From anatomy and epidemiology to occupational therapy and public health, each topic reflects current issues, recent trends, and future directions in health and medicine. By selecting a topic that aligns with your academic interests and career goals, you will have the opportunity to contribute valuable research to the field of health sciences and impact future healthcare practices.

The Range of Health Thesis Topics

Health is one of the most dynamic and multifaceted fields of study, encompassing a wide range of topics that address the well-being of individuals and populations. From anatomy and epidemiology to public health and occupational therapy, health sciences play a crucial role in understanding, preventing, and managing diseases, promoting wellness, and improving healthcare systems. For students pursuing degrees in health and medicine, choosing a thesis topic is an opportunity to delve into pressing health issues, recent trends, and future directions that are shaping the world of healthcare. This article explores the scope of health thesis topics, covering the most significant challenges and emerging research areas within the field.

Current Issues in Health Sciences

The health sciences field faces numerous challenges that require immediate attention. From managing chronic diseases to addressing the impact of infectious diseases, current issues provide students with a broad spectrum of research opportunities.

Chronic Disease Management Chronic diseases, such as diabetes, cardiovascular diseases, and cancer, continue to be leading causes of death worldwide. As populations age and lifestyle-related conditions become more prevalent, managing these diseases is a significant public health challenge. Thesis topics in this area might explore new treatments, prevention strategies, or the role of healthcare policies in managing chronic diseases. Students can also focus on patient education, disease management programs, or the economic burden of chronic diseases on healthcare systems.
Mental Health and Well-being Mental health is another critical area of concern, with issues such as anxiety, depression, and stress becoming more widespread, especially in the wake of global crises like the COVID-19 pandemic. Research in this area could investigate the effectiveness of mental health interventions, the role of healthcare providers in supporting mental health, or the impact of social determinants on mental well-being. Thesis topics might also explore the integration of mental health services into primary care or the role of digital health technologies in improving access to mental health support.
Healthcare Access and Equity Access to quality healthcare remains a challenge, particularly for marginalized communities and populations in low-income regions. The disparities in healthcare access contribute to significant differences in health outcomes. Research on healthcare equity can focus on the social, economic, and political barriers that prevent individuals from accessing care. Thesis topics could explore the effectiveness of public health interventions aimed at improving healthcare access, the impact of healthcare policies on reducing disparities, or the role of technology in bridging the healthcare access gap.

Recent Trends in Health Sciences

Recent technological advancements and shifts in healthcare practices have introduced new trends in health sciences that are transforming patient care and public health approaches. These trends open up exciting research possibilities for students.

Telemedicine and Digital Health Telemedicine has rapidly become a critical component of healthcare delivery, especially during the COVID-19 pandemic. It has improved access to care for patients in remote areas and made healthcare more efficient. Research in this area could explore the effectiveness of telemedicine in improving patient outcomes, the challenges of integrating digital health solutions into traditional healthcare systems, or the role of telemedicine in managing chronic conditions. Thesis topics could also investigate the impact of digital health tools like mobile health apps and wearable devices on patient engagement and self-care.
Personalized Medicine and Genomics Personalized medicine, which tailors treatments to individual genetic profiles, has revolutionized the way we approach disease management. Advances in genomics have enabled healthcare providers to design more effective treatment plans based on a patient’s genetic makeup. Research on personalized medicine could focus on the role of genetic testing in diagnosing and treating diseases, the ethical considerations of gene therapy, or the impact of personalized medicine on cancer treatment outcomes. Other thesis topics might explore the use of precision medicine in managing complex diseases or the integration of genomics into routine healthcare.
Public Health and Preventive Care Public health has shifted its focus toward preventive care, aiming to reduce the prevalence of diseases by addressing their root causes. This shift has led to increased interest in lifestyle interventions, vaccination programs, and health education campaigns that promote wellness and prevent the onset of diseases. Research in this area could explore the effectiveness of public health initiatives in reducing disease burdens, the role of preventive care in managing healthcare costs, or the impact of public health policies on improving population health. Thesis topics could also investigate the role of healthcare providers in promoting preventive care practices.

Future Directions in Health Sciences

Looking ahead, the future of health sciences is being shaped by emerging technologies and evolving healthcare needs. Students have the opportunity to explore these future-oriented topics in their thesis research.

Artificial Intelligence (AI) in Healthcare Artificial intelligence is poised to revolutionize healthcare by enhancing diagnostic accuracy, improving treatment plans, and streamlining administrative tasks. AI-driven tools such as machine learning algorithms, natural language processing, and robotic surgery are already making significant impacts. Research in this area could investigate the role of AI in improving diagnostic precision, the ethical challenges of AI in healthcare, or the impact of AI on reducing medical errors. Thesis topics might also explore how AI can support clinical decision-making or enhance patient engagement through personalized care.
Nanotechnology and Drug Delivery Nanotechnology offers groundbreaking possibilities in drug delivery, enabling precise targeting of diseased cells while minimizing side effects. This innovation is particularly promising in cancer treatment, where nanotechnology can deliver chemotherapy directly to tumor cells. Research could focus on the development of nanomedicine for specific diseases, the challenges of integrating nanotechnology into clinical practice, or the safety and regulatory considerations surrounding nanomedicine. Thesis topics might also explore the role of nanotechnology in enhancing drug efficacy or reducing the toxicity of traditional treatments.
Sustainability in Healthcare As climate change continues to impact public health, sustainability has become a critical consideration in healthcare. Healthcare systems are responsible for a significant share of global carbon emissions, and there is growing interest in reducing the environmental impact of healthcare delivery. Research in this area could explore sustainable healthcare practices, such as reducing energy consumption in hospitals, minimizing medical waste, or adopting eco-friendly medical technologies. Thesis topics might also investigate the role of healthcare policies in promoting sustainability or the impact of climate change on global health.

The field of health sciences offers a vast array of thesis topics that address both current and emerging challenges in healthcare. From managing chronic diseases and improving mental health to harnessing the power of technology in healthcare delivery, students have the opportunity to explore meaningful and impactful research areas. As the world continues to evolve, the future of health sciences will be shaped by innovations in AI, nanotechnology, and sustainability, making it an exciting time for students to contribute to the advancement of healthcare practices. By selecting a thesis topic that reflects their academic and career interests, students can make a significant contribution to the health and well-being of individuals and communities.

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September 26, 2024

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Large-scale study confirms well-established cancer risk factors and identifies new ones

by Institute of Cancer Research

Researchers have examined thousands of genetically defined traits to identify possible causal relationships for eight common cancers. The team evaluated data from more than 860,000 people to uncover potential factors in causing breast, bowel, endometrial, lung, esophageal, ovarian, prostate and kidney cancers.

The study provided supporting evidence for known risk factors, such as obesity and smoking, reaffirming the importance of public health initiatives to reduce the burden of cancer among the population.

It also uncovered previously unexamined traits that might increase people's risk of the disease. The research team at The Institute of Cancer Research, London, has made these associations available online to other researchers, whose follow-up studies may help lead to effective prevention strategies.

The research was published in the journal Nature Communications .

New associations worthy of further investigation

For this study, the researchers accessed datasets comprising 378,142 cases of the eight cancer types of interest, as well as data from 485,715 people without a cancer diagnosis . Using information from published genome-wide association studies , they identified 336,191 relevant genetic variants, which they associated with a total of 3,661 traits—meaning genetically determined characteristics of an individual.

Where possible, the team grouped these traits according to established cancer risk factors, including alcohol consumption and obesity. They then categorized each of the remaining traits as one of the following: cardiometabolic, dietary intake , body composition, immune and inflammatory, fatty acid and lipoprotein metabolism, lifestyle, reproduction, education and behavior, metabolomics and proteomics, or miscellaneous.

The next step was to look for associations between the groups of traits and the cancers being evaluated—for example, seeing whether there was link between different hormone levels and certain types of cancer.

Once an association was made, the team used a hierarchical grading system based on statistical significance to label the likelihood of the relationship being causal. The four options were "robust," "probable," "suggestive" and "non-significant." To support this process, the researchers also drew on evidence from the existing literature.

Overall, the number of robust associations with certain traits was highest for endometrial cancer and lowest for ovarian cancer. The traits most likely to increase the risk of cancer were anthropometric traits—which include metrics such as body mass index (BMI) and waist-hip ratio—while those with the least impact were dietary intake and cardiometabolic factors, such as blood pressure and the balance of fats in the blood.

When it came to specific associations, the study confirmed that cigarette smoking increases the risk of lung cancer; increased BMI raises the risk of colorectal, endometrial, lung, ovarian and renal cancers; higher alcohol consumption increases the risk of endometrial, lung, esophageal, ovarian and renal cancers; and sedentary behavior raises the risk of breast, colorectal, endometrial and lung cancers.

In addition, the study supported less well-known links that different types of cancers have with hormonal factors and with genetically predicted blood levels of various vitamins, minerals and proteins, including vitamin B12, zinc, and cholesterol. The researchers also uncovered a previously unknown association between a genetic marker in a certain type of white blood cell and six of the cancer types.

Taking a new approach

Many earlier studies have already looked at the links between various risk factors and different types of cancers, so the researchers behind the current study decided to approach their work with a different aim.

From the outset, they deliberately kept their study broad. They included a vast number of traits in their research, considered multiple cancer types and used the largest available cancer datasets.

Rather than basing their study around a specific hypothesis, such as "Does physical inactivity increase the risk of ovarian cancer ?" they took an agnostic approach, which allowed them to examine a range of traits with no assumptions or expectations.

Specifically, the team used a technique called Mendelian randomization phenome-wide association study (MR-PheWAS) to try to minimize erroneous results. Joint first author Dr. Molly Went, Analytical Scientist in the Cancer Genomics Group at the ICR, explained, "MR-PheWAS is a statistical technique that uses genetics to provide information about the relationship between a risk factor and an outcome.

"We look to see whether individuals with a genetic propensity to a certain risk factor—for example, becoming addicted to the nicotine in cigarettes—also have a genetic predisposition to a particular outcome, say lung cancer. We generate an association between the genetic basis of these traits, and this allows us to estimate the increased risk that trait gives."

This method helped reduce the risk of reverse causation—where scientists get the cause and effect the wrong way around—and encouraged the team to be aware of alternative factors that might explain any relationships, known as confounding variables.

Findings likely to have long-term scientific impacts

Senior author Professor Richard Houlston, Professor of Molecular and Population Genetics at the ICR, said, "We were pleased to be able to assess multiple traits that have not previously been considered by other researchers. Our work highlighted the complexity of examining traits such as dietary intake, for which it is very hard to disentangle correlations and patterns in the general public's dietary behavior.

"We attempted to overcome this by using extensive cancer datasets and performing a significant number of tests. This gave us the strong evidence we needed to be confident that what we were seeing was not due to chance alone."

Dr. Went added, "This paper is likely to have more impact in the long term. Further molecular and biological follow-up from the cancer research community will help us better understand the basis of the associations identified in this work. To that end, we are delighted to be able to make these associations publicly available. We hope that our results will complement other scientists' independent research.

"In the short term, our research has robustly confirmed well-established risk factors for cancer, such as smoking, alcohol consumption and obesity. In turn, this has reassured us that our methodology is effective in capturing the hazards associated with new risk factors found in the study.

"Going forward, some of the molecular factors identified in the study could serve as potential biomarkers for cancer risk, offering prospective avenues for early detection and prevention strategies."

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J Ovarian Res

Ovulation induction drug and ovarian cancer: an updated systematic review and meta-analysis

1 The First Affiliated Hospital of Nanjing Medical University, The First Clinical Medical College of Nanjing Medical University, Nanjing, 210029 China

2 Department of Gynecology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University，The first clinical medical college of Nanjing Medical University, Nanjing, 210029 China

3 Department of Gynecology, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210036 China

Associated Data

This meta-analysis was based on the data from the published articles and independent of any patient involvement. All the data will be made available to the editors of the journal for review or query upon.

To explore the association between ovulation induction drugs and ovarian cancer.

Systematic review and meta-analysis.

Not applicable.

Women without ovarian cancer who ever or never underwent ovarian induction.

Intervention(s)

An extensive electronic search of the following databases was performed: PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library and CNKI, from inception until January 2022. A total of 34 studies fulfilled our inclusion criteria and were included in the final meta-analysis. The odds ratio (OR) and random-effects model were used to estimate the pooled effects. The Newcastle-Ottawa Scale was used to assess the quality of included studies. Funnel plots and Egger tests were used to assess publication bias.

Main outcomes

New diagnosed borderline ovarian tumor (BOT) and invasive ovarian cancer (IOC) between ovulation induction (OI) group and control (CT) group considering fertility outcome, OI cycles and specific OI drugs.

Primarily, there was no significant difference in the incidence of IOC and BOT between the OI and CT groups. Secondly, OI treatment did not increase the risk of IOC and BOT in the multiparous women, nor did it increase the risk of IOC in the nulliparous women. However, the risk of BOT appeared to be higher in nulliparous women treated with OI treatment. Thirdly, among women exposed to OI, the risk of IOC and BOT was higher in nulliparous women than in multiparous women. Fourthly, the risk of IOC did not increase with increasing OI cycles. Lastly, exposure to specific OI drugs also did not contribute to the risk of IOC and BOT.

Overall, OI treatment did not increase the risk of IOC and BOT in most women, regardless of OI drug type and OI cycle. However, nulliparous women treated with OI showed a higher risk of ovarian cancer, necessitating their rigorous monitoring and ongoing follow-up.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13048-022-01084-z.

Introduction

Infertility affects more than 48.5 million couples worldwide [ 1 – 3 ]. It is emerging as a public health problem, driving the demand for assisted reproductive treatment [ 4 ]. Ovulation induction (OI) is a process in which the ovaries are drugged to stimulate the production of many follicles containing eggs, which usually begins early in the menstrual cycle. OI treatment is highly desirable, especially for isolated anovulatory infertility [ 5 ]. OI treatment is associated with ovarian hyper-stimulation and multiple follicular ovulations. As we know, ovulation is a common injurious process associated with an inflammatory response and destruction of ovarian epithelial cells [ 6 , 7 ]. According to the incessant ovulation and gonadotropin hypothesis, high levels of gonadotropin and excessive ovulation may engage patients into repeated cycles of injury, inducing inflammation and regeneration, which could potentially increase the risk of ovarian cancer by inducing somatic cell mutations [ 8 – 10 ]. Previous studies have debated whether OI could increase the risk of invasive ovarian cancer (IOC) and borderline ovarian tumors (BOT) [ 11 , 12 ]. Although most studies have concluded that OI does not contribute to the risk of IOC and BOT, some scholars still proposed that OI may be associated with them. Therefore, we performed this updated systematic review and meta-analysis to find out whether exposure to OI treatment significantly increases the risk of IOC and BOT.

Materials and methods

Search strategy.

The PRISMA guidelines were used for this study. A systematic literature search was then conducted in PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library and CNKI, which included records up to January 2022. The main keywords included the following domains of Medical Subject Heading terms: “ ovulation induction “ and “ ovarian cancer “. The retrieval strategy adopted the combination of subject terms and free words. These terms were then combined with “AND” or “OR”. Also, to broaden the search, review articles were used to ensure that all relevant citations were identified and imported.

Study screening

Two independent researchers (YL and WQQ) simultaneously screened the titles, abstracts and full text of the literature according to the inclusion and exclusion criteria. Any disagreements were discussed and solved by consensus or third-party arbitration (ZS). The inclusion criteria were as follows: (1) Cohort studies and case-control studies with adequate samples; (2) Exposure to ovulation induction drugs such as clomiphene citrate (CC), gonadotrophin (GDT) and gonadotropin-releasing hormone analogs (GnRH-a); (3) Follow-up in the cohort study was sufficiently long to demonstrate treatment differences; (4) The study had a clear description of the exposure to OI drugs and essential information about enrolled patients;(5) The type of cancer included borderline ovarian tumor (BOT) or invasive ovarian cancer (IOC). The exclusion criteria were as follows: (1) Non-English or Non-Chinese literature; (2) Non-human studies; (3) Literature with incomplete data; (4) Duplicate and inaccessible literature.

Data extraction

Two independent researchers (YL and SJF) performed the data extraction after viewing the complete manuscripts of the eligible literature. Relevant data was input into separate spreadsheets and then cross-checked by each researcher to maintain the quality of the data. The data of bibliography (year and author), study design (sample size, study type, study duration and study location), outcome measures (cancer type and incidence of individual ovarian cancers in group) and other endpoint evaluation (fertility outcome, OI drug type and OI cycles) were extracted from each study. If necessary, discussions with the third-party arbitration (XW) would solve all disputes.

Quality evaluation

Two researchers (YL and YWN) independently assessed the quality of the literature by using the NOS scale (Newcastle-Ottawa Scale). The main components of the NOS scale included: patient selection, intergroup comparability and outcome measurement [ 13 ]. Disagreements were solved by consensus or third-party arbitration (WXL) when they appeared. A total score of more than 6 was considered to be of satisfactory quality [ 14 ].

Statistical analysis

Data aggregation and basic meta-analysis.

The meta-analysis was performed by using STATA 12.0. Binary variables were evaluated by odds ratio (OR) and its 95% confidence interval (95% CI). P < 0.05 was regarded as statistically significant.

Depending on heterogeneity, the appropriate model (random or fixed) was then selected to merge the outcome indicators [ 15 ]. The I 2 value less than 50% were deemed to be low heterogeneity, 51–75% were deemed to be moderate heterogeneity, and greater than 75% were deemed to be high heterogeneity [ 16 ]. If the I 2 value exceeded 50%, the random-effect model was chosen. Otherwise, if the I 2 value was less than 50%, both the random effects and fixed effects models were acceptable [ 17 ].

Assessment of publication bias

In principle, funnel plot analyses were performed to accompany meta-analyses involving more 10 studies and to judge the publication bias [ 18 ]. If there was no significant publication bias, the funnel plot was supposed to be symmetrical. A complementary approach for funnel plots was to perform Egger’s test to objectively measure bias [ 19 ].

Details of ethical approval

This meta-analysis was based on the data from published articles and independent of any patient participation. As such, institutional review board (IRB) approval was not required.

Study characteristics and quality evaluation

A flowchart detailing the process of identification and inclusion for the target literature was shown in Supplemental Material Fig. 1 . Three hundred seven articles were included in the initial screening phase. Of these articles, 42 articles met the criteria for full-text review. Finally, a total of 34 articles were included in the meta-analysis, 14 of which were case-control studies and 20 of which were cohort studies. The final meta-analysis included a total of 3,643,303 participants. All the included literature was of adequate quality. The quality evaluation of the included literature was presented in Supplemental Material Table S1 .

Part I: the risk of ovarian cancer between OI and CT group

Of the 34 studies, 12 reported BOT [ 12 , 20 – 30 ] and 30 reported IOC [ 11 , 12 , 20 , 21 , 23 – 26 , 29 , 31 – 51 ]. Basic information of the included studies was given in Supplemental Material Table S2 . For further study, we conducted subgroup analyses to assess the risk of IOC and BOT between groups according to study type.

The cancer risk between groups in case-control study

In the subgroup analysis of case-control studies, 12 studies reported IOC [ 11 , 23 , 29 , 32 , 36 – 43 ] and 5 studies reported BOT [ 23 , 27 – 30 ]. Among these studies, only 1 study showed a significantly higher risk of IOC in the OI group than in the CT group [ 11 ] and 3 studies showed a higher risk of BOT in the OI group than in the CT group [ 28 – 30 ]. Pooled result indicated that the risk of IOC (OR = 1.09, 95%CI: 0.88–1.35, I 2 = 54.9%, Table Table1, 1 , Fig. Fig.1A) 1 A) and BOT (OR = 1.90, 95%CI: 0.89–4.09, I 2 = 73.4%, Table Table1, 1 , Fig. Fig.1B) 1 B) did not show significant difference between groups.

Odd ratios (with confidence intervals) and heterogeneity for each of the cancer risks analysed

Outcome	OR	95% CI	I	Degree of heterogeneity
The risk of IOC between OI and CT group (based on case-control study)	1.09	0.88-1.35	54.9%	Moderate
The risk of BOT between OI and CT group (based on case-control study)	1.90	0.89-4.09	73.4%	Moderate
The risk of IOC between OI and CT group (based on cohort study)	1.11	0.91-1.35	21.8%	Low
The risk of BOT between OI and CT group (based on cohort study)	1.34	0.97-1.83	50.5%	Moderate
The risk of IOC between OI and CT group (in multiparous women)	0.83	0.65-1.05	21.3%	Low
The risk of BOT between OI and CT group (in nulliparous women)	1.17	0.55-2.48	73.5%	Moderate
The risk of IOC between OI and CT group (in nulliparous women)	1.55	0.94-2.57	69.5%	Moderate
The risk of BOT between OI and CT group (in nulliparous women)
The risk of IOC between the nulliparous and multiparous women (with ovulation induction treatment)
The risk of BOT between the nulliparous and multiparous women (with ovulation induction treatment)
The risk of IOC between OI and CT group (less than 3 ovulation induction cycles)	1.05	0.72-1.52	42.9%	Low
The risk of IOC between OI and CT group (more than 3 ovulation induction cycles)	0.98	0.79-1.22	0%	Low
The risk of IOC between OI and CT group (less than 6 ovulation induction cycles)	0.85	0.64-1.12	0%	Low
The risk of IOC between OI and CT group (more than 6 ovulation induction cycles)	0.88	0.59-1.31	0%	Low
The risk of IOC between OI and CT group (less than 12 ovulation induction cycles)	0.87	0.69-1.10	0%	Low
The risk of IOC between OI and CT group (more than 12 ovulation induction cycles)	0.78	0.49-1.22	0%	Low
The risk of IOC between CC and CT group	1.01	0.88-1.17	0%	Low
The risk of BOT between CC and CT group	1.32	0.79-2.21	72.6%	Moderate
The risk of IOC between GDT and CT group	1.08	0.80-1.44	0%	Low
The risk of BOT between GDT and CT group	1.73	0.88-1.93	54.1%	Moderate
The risk of IOC between HCG and CT group	1.10	0.71-1.71	34.7%,	Low
The risk of BOT between HCG and CT group	1.28	0.71-2.31	56%	Moderate
The risk of IOC between HMG and CT group	1.07	0.44-2.57	71.6%	Moderate
The risk of BOT between HMG and CT group	5.31	0.73-38.72	83.3%	High
The risk of IOC between GnRH-a and CT group	0.49	0.07-3.66	71.9%	Moderate

CC Clomiphene citrate, GDT Gonadotrophin, GnRH-a Gonadotropin-releasing hormone analogues, HCG human menopausal gonadotropin, HMG human chorionic gonadotropin, IOC invasive ovarian cancer, BOT borderline ovarian tumor, OI ovulation induction group, CT control group, OR odds ratio, 95%CI 95% confidence interval

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A Forest plot of IOC risk between OI group and CT group based on case-control studies; B Forest plot of IOC risk between OI group and CT group based on cohort studies; C Forest plot of BOT risk between OI group and CT group based on case-control studies; D Forest plot of BOT risk between OI group and CT group based on cohort studies

The cancer risk between groups in cohort study

In the subgroup analysis of cohort studies, 18 studies reported IOC [ 12 , 20 , 21 , 24 – 26 , 31 , 33 – 35 , 44 – 51 ] and 7 studies reported BOT [ 12 , 20 – 22 , 24 – 26 ]. Of these studies, 3 studies showed a higher risk of IOC [ 12 , 21 , 31 ] in the OI group than in the CT group and 3 studied showed a higher risk of BOT in the OI group than in the CT group [ 21 , 24 , 25 ]. Again, the results showed no significant difference between groups in the incidence of IOC (OR = 1.11, 95%CI: 0.91–1.35, I 2 = 21.8%, Table Table1, 1 , Fig. Fig.1C) 1 C) and BOT (OR = 1.34, 95%CI: 0.97–1.83, I 2 = 50.5%, Table Table1, 1 , Fig. Fig.1 1 D).

Part II: the incidence of ovarian cancer between OI and CT group according to fertility outcome

In this section, we sought to find out whether the multiparous and nulliparous women treated with OI presented an increased risk of ovarian tumors when compared to those who had not been treated with OI. Relevant data were presented in Supplemental Material Table S3 .

The cancer risk between groups in multiparous women

Firstly, 10 studies of IOC [ 11 , 12 , 34 , 36 – 38 , 40 – 42 , 50 ] and 3 studies of BOT [ 12 , 22 , 28 ] analyzed the risk of ovarian cancer in multiparous women with or without OI treatment. None of these studies demonstrated a higher risk for IOC and BOT in the OI group. Pooled result remained consistent, indicating that OI treatment did not increase the risk of IOC (OR = 0.83, 95%CI: 0.65–1.05, I 2 = 21.3%, Table Table1, 1 , Fig. 2 A) and BOT (OR = 1.17, 95%CI: 0.55–2.48, I 2 = 73.5%, Table Table1, 1 , Fig. Fig.2B) 2 B) in multiparous women.

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A Forest plot of IOC risk between OI group and CT group in multiparous women; B Forest plot of BOT risk between OI group and CT group in multiparous women; C Forest plot of IOC risk between OI group and CT group in nulliparous women; D Forest plot of BOT risk between OI group and CT group in nulliparous women

The cancer risk between groups in nulliparous women

In the second part, 8 studies of IOC [ 11 , 12 , 34 , 36 , 38 , 40 – 42 ] and 3 studies of BOT [ 12 , 22 , 28 ] reported the risk of ovarian cancer in nulliparous women with or without OI treatment. Of these studies, only 1 study showed a significantly higher risk of IOC in the OI group than in the CT group [ 11 ]. The summarized result for IOC showed no difference in cancer risk between groups (OR = 1.55, 95%CI: 0.94–2.57, I 2 = 69.5%, Table Table1, 1 , Fig. Fig.2C). 2 C). Additionally, none of these studies reported a higher risk of BOT in the OI group. However, after pooled analysis, the risk of BOT appeared to be higher in nulliparous women treated with OI than in those nulliparous women who had not been treated with OI (OR = 1.49, 95%CI: 1.03–2.15, I 2 = 0%, Table Table1, 1 , Fig. Fig.2 2 D).

Part III: the risk of ovarian cancer between the multiparous and nulliparous women in OI group

In this chapter, we attempted to figure out the differences in cancer risk between the multiparous and nulliparous woman in the OI group. Relevant data were presented in Supplemental Material Table S4 . In total, 8 studies of IOC [ 11 , 12 , 34 , 36 , 38 , 40 – 42 ] and 3 studies of BOT [ 12 , 22 , 28 ] reported on the risk of ovarian cancer in the nulliparous and multiparous women treated with OI. The summarized results showed a significantly higher risk of IOC (OR = 3.35, 95%CI: 2.10–5.34, I 2 = 52.2%, Table Table1, 1 , Fig. 3 A) and BOT (OR = 2.58, 95%CI: 1.76–3.79, I 2 = 0%, Table Table1, 1 , Fig. Fig.3B) 3 B) in the nulliparous women treated with OI than in those multiparous women treated with OI.

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A Forest plot of IOC risk between nulliparous and multiparous women with OI treatment; B Forest plot of BOT risk between nulliparous and multiparous women with OI treatment

Part IV: the relationship between number of OI cycles and cancer risk

Then, we tried to find out whether cancer risk increased with more OI cycles. Totally, 8 studies provided relevant data for IOC [ 20 , 24 , 25 , 36 , 39 , 41 , 42 , 46 , 47 ]. Regrettably, data for BOT were not available for meta-analysis. Relevant data were presented in Supplemental Material Table S5 .

Using a cut-off of 3 cycles, we did not find a higher cancer risk in those women who received less than 3 cycles when compared to the CT group (OR = 1.05, 95%CI: 0.72–1.52, I 2 = 42.9%, Table Table1, 1 , Fig. 4 A). Meanwhile, we found a similar result in those women who received more than 3 cycles (OR = 0.98, 95%CI: 0.79–1.22, I 2 = 0%, Table Table1, 1 , Fig. Fig.4A). 4 A). Using 6 cycles as a cut-off, those women who received less than 6 cycles did not present an increased cancer risk when compared to the CT group (OR = 0.85, 95%CI: 0.64–1.12, I 2 = 0%, Table Table1, 1 , Fig. Fig.4B) 4 B) and a similar result was found in those women who received more than 6 OI cycles (OR = 0.88, 95%CI: 0.59–1.31, I 2 = 0%, Table Table1, 1 , Fig. Fig.4B). 4 B). Lastly, using 12 cycles as a cut-off, we did not find a significantly increased cancer risk in those women who received less than 12 cycles when compared to the CT group (OR = 0.87, 95%CI: 0.69–1.10, I 2 = 0%, Table Table1, 1 , Fig. Fig.4C). 4 C). Also, a similar result was found in those women who received more than 12 OI cycles (OR = 0.78, 95%CI: 0.49–1.22, I 2 = 0%, Table Table1, 1 , Fig. Fig.4 4 C).

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A Forest plot of IOC risk between OI group and CT group based on a cut-off value of 3 cycles; B Forest plot of IOC risk between OI group and CT group based on a cut-off value of 6 cycles; A Forest plot of IOC risk between OI group and CT group based on a cut-off value of 12 cycles

Part V: the relationship between specific OI treatment and cancer risk

At last, we wished to find out whether specific OI drugs were associated with an increased cancer risk. For further study, we divided the subjects into three groups according to the type of OI drug. These were the clomiphene citrate group (CC), the gonadotrophin group (GDT) and the gonadotropin-releasing hormone analog group (GnRH-a). Relevant data were provided in Supplemental Material Table S6 .

The relationship between CC and cancer risk

We firstly analyzed the relationship between CC and cancer risk. This part of analysis included 17 studies of IOC [ 25 , 29 , 35 , 36 , 38 , 41 – 43 , 45 – 47 , 50 , 51 ] and 7 studies of BOT [ 12 , 20 , 22 , 25 , 27 – 29 ]. Only 1 study reported a higher cancer risk in the CC group than in the CT group [ 12 ]. However, pooled results showed that the risk of IOC (OR = 1.01, 95%CI: 0.88–1.17, I 2 = 0%, Table Table1, 1 , Fig. 5 A) and BOT (OR = 1.32, 95%CI: 0.79–2.21, I 2 = 72.6%, Table Table1, 1 , Fig. Fig.5A) 5 A) were not significantly higher in the CC group when compared to the CT group.

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A Forest plot of IOC and BOT risk between CC group and CT group; B Forest plot of IOC and BOT risk between HMG group and CT group; C Forest plot of IOC and BOT risk between HCG group and CT group; D Forest plot of IOC and BOT risk between GDT group and CT group; E Forest plot of IOC risk between GnRH group and CT group

The relationship between GDT and cancer risk

Secondarily, we focused our attention on GDT and performed a subgroup analysis in this section. GDTs mainly consisted of human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG). However, some studies did not further categorized GDT. For IOC, there were 5 studies of HMG [ 29 , 35 , 38 , 41 , 47 ], 2 studies of HCG [ 38 , 43 ] and 6 studies of unclassified GDT [ 25 , 33 , 36 , 43 , 49 , 51 ]. Only 1 study reported a higher cancer risk in HMG group than in the CT group [ 29 ]. Nevertheless, pooled results indicated that HMG (OR = 1.07, 95%CI: 0.44–2.57, I 2 = 71.6%, Table Table1, 1 , Fig. Fig.5B), 5 B), HCG (OR = 1.10, 95%CI: 0.71–1.71, I 2 = 34.7%, Table Table1, 1 , Fig. Fig.5C) 5 C) and unclassified GDT (OR = 1.08, 95%CI: 0.80–1.44, I 2 = 0%, Table Table1, 1 , Fig. Fig.5D) 5 D) did not increase the cancer risk.

While for BOT, 2 studies of HMG [ 28 , 29 ], 2 studies of HCG [ 22 ] and 3 studies of GDT [ 22 , 25 , 27 ] were included in this part of analysis. Consistently, we found similar results that HMG (OR = 5.31, 95%CI: 0.73–38.72, I 2 = 83.3%, Table Table1, 1 , Fig. Fig.5B), 5 B), HCG (OR = 1.28, 95%CI: 0.71–2.31, I 2 = 56%, Table Table1, 1 , Fig. Fig.5C) 5 C) and unclassified GDT (OR = 1.73, 95%CI: 0.88–1.93, I 2 = 54.1%, Table Table1, 1 , Fig. Fig.5D) 5 D) did not increase tumor risk.

The relationship between GnRH-a and cancer risk

Thirdly, we only found 2 studies which provided analyzable data on the relationship between the risk of IOC and GnRH-a [ 43 , 47 ]. Along the same lines, we did not find an increased risk of IOC (OR = 0.49, 95%CI: 0.07–3.66, I 2 = 71.9%, Table Table1, 1 , Fig. Fig.5E) 5 E) in the GnRH-a group when compared to the CT group. However, it was regrettable that another meta-analysis focusing on the relationship between the risk of BOT and GnRH-a could not be performed due to lack of data.

Publication bias

In our analysis, funnel plot analysis and Egger regression analysis were performed to judge the publication bias of the included studies. Neither the funnel plot (Supplemental Material Fig. 2 A) nor the Egger test showed evidence of publication bias in our analysis (Supplemental Material Fig. 2 B).

The following points are currently discussed regarding the possible induction of ovarian cancer with the use of OI drugs: (1) the incessant ovulation hypothesis stated that ovarian epithelium could be destroyed and repaired during uninterrupted ovulation. When a sufficient amount of damage is caused, malignant transformation of ovarian epithelial cells will be triggered [ 8 ]. Furthermore, cancer risk had been found to decrease with increasing numbers of pregnancies and live births, longer duration of breastfeeding and use of oral contraceptives [ 52 – 57 ]. The effects of these anovulation factors confirmed the above observations. Thus, it is thought that the number of ovulatory cycles during the lifetime was associated with ovarian cancer risk, this finding has been observed in several animal models and epidemiological studies [ 58 – 62 ]. (2) The gonadotropin hypothesis suggested that excess gonadotropins could hyper-stimulate the ovaries and induce estrogen production. The amount of estrogen secreted in one gonadotropin-stimulated cycle was equivalent to the total production of natural cycles over a two-year period [ 63 ]. Meanwhile, there appeared to be growing evidence that estrogen conferred increased ovarian cancer risk [ 64 – 66 ]. Thus, gonadotropin-induced elevated estrogen levels might promote the malignant transformation of normal ovarian epithelium [ 63 , 67 ]. The above hypotheses had been tested in hen models but not in humans [ 68 , 69 ]. Therefore, speculation regarding the relationship between the use of ovulation induction drug use and ovarian cancer development continues.

Research in this area was based on cohort studies, case series and case-control studies. And, there were still no randomized controlled trials regarding the relationship between ovulation inducing drugs and ovarian cancer due to ethical issues, the relatively low incidence of ovarian cancer and recall bias after ovulation induction [ 70 ]. This updated systematic review and meta-analysis was based on cohort studies and case-control studies. Some of included studies provided supportive evidence that OI treatment might increase the risk of IOC. However, according to subgroup analysis based on study type, we found no convincing evidence that OI treatment could induce an increased risk of IOC. Compared with previous systematic reviews [ 71 , 72 ], we expanded our search to include more recent studies in our analysis and obtained consistent results.

BOTs are morphologically similar to IOCs and follow a similar pathogenesis [ 73 , 74 ]. As the etiology of BOT was still unknown, it was difficult to explain the possible causal relationship between infertility and OI drugs. In our analysis, no significant increased risk of BOT was found following OI treatment, which appeared to contradict the increasing risk of BOT reported by Barcroft et.al (OR = 1.69, 95%CI: 1.27–2.25). With more studies included in our pooled analysis, we used further subgroup analyses based on study type to circumvent the heterogeneity issues caused by retrospective studies. Ultimately, the results of subgroup analysis were highly consistent in that OI treatment did not increase the risk of BOT.

In addition, during the review of the literature, we found several studies supporting that OI treatment could induce an increased risk of ovarian cancer in the nulliparous women [ 11 , 12 ]. A cumulative analysis conducted by Whittemore et.al indicated an increased risk of ovarian cancer (OR = 27.0, 95%CI: 2.3–315.6) in the nulliparous women who ever received OI treatment. Reigstad et.al also noted a greater increased risk of ovarian cancer (HR 2.49, 95% CI 1.30 to 4.78) in the nulliparous women treated with OI. As we know, parity was known as an established protective factor for ovarian cancer [ 75 ]. Previous studies have shown that the greatest reduction in ovarian cancer risk was associated with the first pregnancy and each subsequent pregnancy could also reduce the risk of ovarian cancer [ 11 , 75 , 76 ]. This protective mechanism has been attributed to anovulation, reduced gonadotropin production and increased progesterone levels [ 77 ]. Hence, whether OI treatment would increase the ovarian cancer risk in nulliparous and multiparous women remained controversial. Therefore, we conducted supplementary analyses based on fertility outcomes in light of the above questions. Among the multiparous women, we did not find a higher risk of IOC and BOT in the OI group than in the CT group. Similarly, among the nulliparous women, OI treatment also did not increase the risk of IOC. However, an increased risk of BOT was found in the nulliparous women treated with OI when compared to those nulliparous women who had not been treated with OI. Nonetheless, none of these included studies initially reported a higher risk of BOT in nulliparous women treated with OI. Based on a review of the included studies, this finding might be due to a lack of ovulatory pause caused by pregnancy and exposure to ovarian hyper-stimulation [ 8 – 10 , 12 ]. Notably, the BOTs were generally seen in younger women [ 78 – 81 ]. Hence, the above association might also be due to a diagnostic bias occurring in young nulliparous women who might pursue medical attention and undergo intensive monitoring [ 41 ].

Rodriguez et.al previously found that infertility itself might increase ovarian cancer risk without concomitant exposure to OI drugs [ 82 ]. A current meta-analysis based on nine prospective cohort studies also suggested that infertility in women was associated with an increased risk of ovarian cancer [ 83 ]. Moreover, a number of diseases that cause infertility, including polycystic ovary syndrome (PCOS) and endometriosis, had been found to be associated with ovarian cancer development. Previous studies had indicated that the genetic and epigenetic profile of patients with PCOS was similar to that of ovarian cancer [ 84 ]. Further, the risk of ovarian cancer, particularly serous borderline ovarian tumor, was shown to be increased in patients with PCOS [ 85 – 87 ]. We also found that ovarian clear cell carcinoma and endometrioid carcinoma were most often associated with ovarian endometriosis in previous studies [ 88 , 89 ]. Thus, infertility itself might be an independent risk factor for ovarian cancer [ 90 ]. In parallel, whether there existed a difference in cancer risk between nulliparous and multiparous women treated with OI was under discussion, as it was difficult to separate OI treatment from infertility as a risk factor for ovarian cancer. In our analysis, we used OI exposure as a control variable to evaluate the relationship between infertility and ovarian cancer and found that the nulliparous women treated with OI showed a higher risk of IOC and BOT than those multiparous women treated with OI. Nieto et.al performed a retrospective study of ovarian cancer in first-degree relatives of infertile patients and showed an increased risk of ovarian cancer in infertile patients who failed to conceive despite receiving OI treatment, which supported our findings [ 91 ]. Rizzuto et.al also noted that the risk of BOT was slightly higher in nulliparous women treated with OI than in multiparous women [ 72 ]. In summary, we believed that there was a necessity to conduct a rigorous medical follow-up in those nulliparous patients treated with OI. Consistent with previous studies, the vast majority of patients were found within 5 years after ovulation induction [ 92 – 98 ]. In our analysis, the included cohort studies had a follow-up period of more than 5 years, which in our opinion is sufficient to detect ovarian cancer. Therefore, follow-up periods longer than 5 years should be considered.

Indeed, it would be arbitrary to diagnose the relationship between OI and ovarian cancer solely based on the history of OI exposure. According to incessant ovulation hypothesis, more ovulatory cycles appeared to be associated with a higher risk of developing ovarian cancer [ 75 , 99 , 100 ]. Whether such a cumulative effect exists remained controversial. After reviewing previous studies, we found no meta-analysis reported an association between OI cycles and the risk of ovarian cancer. Thereby, we performed a further subgroup analysis based on OI cycles, which was the focal point of our analysis. In our analysis, we used 3, 6 and 12 OI cycles as cut-off points, respectively. Compared to the control population, we found no correlation between increasing OI cycles and increased cancer risk. Unfortunately, the data for BOT in this aspect were not available for meta-analysis.

In accession, several studies had reported the risk of individual ovarian cancers due to specific OI drug exposure [ 12 , 29 , 101 ]. Consequently, for further study, we performed subgroup analyses according to the type of OI drug to assess whether specific OI drugs would increase the risk of ovarian cancer. CC was the most common drug to induce ovulation, especially in patients with ovulatory disturbances [ 102 ]. Reigstad et.al reported an increased risk of cancer in nulliparous women exposed to CC (HR = 2.5, 95%CI: 1.3–4.8). Rossing et.al also reported an increased ovarian tumor risk in women exposed to CC (SIR = 2.5, 95%CI: 1.3–4.5). A current meta-analysis conducted by Barcroft et.al supported the view mentioned above, which concluded that the exposure to CC was associated with a significant increased cancer risk (OR = 1.40, 95%CI: 1.10–1.77). However, in our meta- analysis, we included additional studies but did not find an increased cancer risk in those women exposed to CC. GDTs were also commonly used in women with proven hypopituitarism and in women who were not sensitive to CC [ 103 , 104 ]. Shan et.al reported a slight increased ovarian cancer risk in women exposed to HMG (OR = 3.95, 95%CI: 1.3–12.2). While in our study, we found that GDTs were not associated with an increased risk of IOC and BOT. GnRH-a was introduced in anovulatory women, which could reproduce spontaneous menstrual cycle and induce ovulation [ 105 , 106 ]. Our findings indicated that GnRH-a did not increase the risk of IOC. Due to the lack of the data on BOT risk in women exposed to GnRH-a, further meta-analysis could not be performed. In summary, CC, GDT and GnRH-a were proven to be safe for OI treatment without increasing ovarian tumor risk.

Most of our findings were generally consistent with previous studies on this topic [ 71 , 72 , 107 , 108 ]. A new study was included in this latest update of the systematic review and meta-analysis compared to previous studies in this area. This study provides new data on the risk of BOT and IOC to CC exposure. To assess the impact of the latest studies on the outcome of this update, an additional sensitivity analysis was conducted. The sensitivity analysis without the latest study did not change the results that exposure to CC did not increase the risk of IOC (OR = 1.05, 95%CI: 0.89–1.21) and BOT (OR = 1.73, 95%CI: 0.96–2.50). And this latest study made the results more reliable. The results of the sensitivity analysis were shown in Supplemental Material Table S7 . To summarize, OI treatment was relatively safe and cancer risk was not increased more cycles of OI and specific OI drugs. However, for those nulliparous women treated with OI, they appeared to have a higher tumor risk. Therefore, rigorous monitoring and sufficiently long follow-up were necessary for these women.

Strengths and limitations of the study

This study included 34 studies from around the world and provided an up-to-date meta-analysis to explore the potential impact of OI treatment on ovarian cancer risk. The inclusion and exclusion criteria for this systematic review and meta-analysis had been made more rigorous. In addition, the included studies were updated and the process of meta-analysis was made more rigorous. In our analysis, lessons learned from previous studies were incorporated and further subgroup analyses were conducted based on study type, tumor type, parity, OI cycle and specific OI drugs. Of note, this meta-analysis was the first study to evaluate the relationship between the OI cycles and ovarian cancer.

However, our study still had some objective shortcomings. Firstly, further work should focus more attention on patient demographics and specific data including drug combinations, cycles of use, use dosage and administration methods. Secondly, loss of follow-up existed in included studies in our analysis and retrospective studies were always considered to be lower quality evidence due to the presence of recall bias. We needed more large and long-term prospective cohort studies with careful follow-up. Thus, follow-up process needed to be improved. Last but not least, the formation of symbiotic relationships between cancer registries and fertility services should be encouraged to link fertility data with cancer information. Communication and collaboration between fertility services should also be encouraged in order to collect adequate data. We believe that further exploration in this area will facilitate the further development of reproductive science.

Conclusions

OI treatment did not increase risk of ovarian cancer, regardless of treatment regimen and treatment cycle. However, nulliparous women treated with OI might have an increased risk of BOT compared to the nulliparous women not treated with OI. Meanwhile, nulliparous women treated with OI appeared to have a higher risk of IOC and BOT than multiparous women treated with OI. In view of the above, OI treatment was relatively safe but those nulliparous women treated with OI must be followed up rigorously.

Abbreviations

OI	Ovulation induction
OR	Odds ratio
BOT	Borderline ovarian tumor
IOC	Invasive ovarian cancer
CC	Clomiphene citrate
GDT	Gonadotrophin
GnRH-a	Gonadotropin-releasing hormone analogues

Authors’ contributions

YL & SJF performed the database search. YL & WQQ collected the data. YL performed the analysis and wrote the manuscript. ZS & XW supplemented the database search, polished the language of the article and provided third party arbitration. WXL provided guidance on research directions. All the authors participated in this analysis and approved the final version of the manuscript.

This work was supported by Jiangsu Provincial Commission of Health and Family Planning scientific research project (H2018017), Jiangsu Provincial Women’s and Children’s Health key talent project (RC201709).

Availability of data and materials

Declarations.

All authors agreed publication of the manuscript.

The authors declare no financial, personal, intellectual and professional conflicts of interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Liang Yu, Jiafan Sun, Qiqin Wang and Wennian Yu contributed equally to this work.

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Matthew Block, M.D., Ph.D., a Mayo Clinic medical oncologist, and Keith Knutson, Ph.D., a Mayo Clinic researcher, are developing a vaccine to prevent ovarian cancer tumors from returning in people with advanced ovarian cancer whose tumors have recurred after surgery and chemotherapy. White blood cells are extracted from a blood draw and ...
Ovarian Cancer Research Highlights
The ACS funds scientists who conduct research about ovarian cancer at medical schools, universities, research institutes, and hospitals throughout the United States. We use a rigorous and independent peer review process to select the most innovative research projects proposals to fund. These grant statistics are as of July 15, 2024.
Ovarian Cancers: Evolving Paradigms in Research and Care
Chapter 3 builds on this to discuss research on the prevention and early detection of ovarian cancers. On the topic of risk assessment, the chapter includes discussions of a wide range of genetic and nongenetic risk factors for the development of an ovarian cancer, risk-prediction models, and genetic testing. ... SU2C-ovarian cancer research ...
Ovarian Cancer Essays: Examples, Topics, & Outlines
Ovarian Cancer What Exactly Is. Pages: 8 Words: 3456. A mutation of the gene causing colorectal cancer or epithelial ovarian cancer are major risk factors for ovarian cancer, and genetic testing within the laboratory can identify most of these. However, the women who possess these inherited genes are at less risk than those women who do not ...
Current and Emerging Methods for Ovarian Cancer Screening and
1. Introduction. The term "ovarian cancer" (OC) encompasses a heterogeneous group of carcinomas that form in ovarian tissue, and which present with distinct clinicopathological and molecular features along with unique tissue origins [].Among them, ovarian high-grade serous carcinoma (HGSC) accounts for approximately 70-80% of all ovarian cancer diagnoses [2,3] and is the most lethal ...
Health Thesis Topics
1. Anatomy Thesis Topics. The impact of aging on muscle mass and function. Investigating the anatomical variations in the human liver. The role of the lymphatic system in cancer metastasis. Exploring the anatomy of the human brain in neurodegenerative diseases. Anatomical changes in the cardiovascular system due to hypertension.
Large-scale study confirms well-established cancer risk factors and
Principles of Mendelian randomization (MR) and study overview. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-46927-z
Ovulation induction drug and ovarian cancer: an updated systematic
Previous studies have shown that the greatest reduction in ovarian cancer risk was associated with the first pregnancy and each subsequent pregnancy could also reduce the risk of ovarian cancer [11, 75, 76]. ... Most of our findings were generally consistent with previous studies on this topic [71, 72, 107, 108]. A new study was included in ...