Disparities in Gynecologic Cancers.

Ovarian cancer remains the most lethal gynecologic cancer with an estimated 19,710 cases and over 13,000 deaths estimated in 2023 in the U.S. 6 Ovarian cancer is a heterogenous disease including epithelial ovarian cancer (EOC) representing over 80% of ovarian cancers (e.g., high and low grade serous, clear cell carcinoma), stromal cancers and germ cell tumors with different age and race distributions and survival outcomes. Most data at the population level reflects the EOC predominance. The high lethality and poor prognosis of EOC often obscures disparities among groups and ignores modifiable factors including access to higher volume specialty care. Over the past 20 years, ovarian cancer incidence has decreased (−2.9% annual percent change noted 2015–2019) and overall survival has minimally increased (51.5% relative 5-year survival). Though ovarian cancer is less commonly diagnosed in Black women compared to NHW (8.9 vs 10.5 per 100,000 women), survival has been consistently worse. Black women are diagnosed at later stages overall and may be diagnosed at younger ages. SEER data (2013–2019) show the 5-year relative survival rates to be lowest for non-Hispanic Black women (42.3%) and American Indian/Alaska Native women (45%) when compared to NHW women (49.8%). 49 Several large studies and meta-analyses have consistently shown increased mortality rates of up to 18–29% in Black women, 50 , 51 but no differences in mortality when comparing Hispanic or Asian women to NHW women. Disaggregated SEER data showed different incidence among Asians with highest rates in Asian Indian/Pakistani women and lowest in Korean women. 52 Insurance status, lower education attainment, and lower socioeconomic status have also been associated with higher mortality irrespective of race and ethnicity. A recent CDC funded Ovarian Cancer Executive Review Conference summarizes this literature and found disparities in domains of guideline concordant treatment, genetic testing, geographic barriers, and treatment at high volume centers. 53 There is no acceptable standard blood or radiologic screening test for ovarian cancer for average risk patients, so risk reduction strategies have focused on traditional modifiable epidemiologic factors and early detection by symptom recognition and triage. Early recognition of ovarian cancer symptoms and referral to gynecology or gynecologic oncology is critical but improved survival once a patient has significant symptoms has been harder to establish. Biases among providers and the public that non-white women are not at risk for EOC remain are being slowly countered by increased advocacy efforts. Traditional risk factors for increased ovarian cancer include obesity, early menarche, late menopause, nulliparity, endometriosis, and family history (hereditary cancer syndromes), while tubal ligation and oral contraceptive (OCP) use are protective. Most studies are limited by a low proportion of non-white patients. The Ovarian Cancer in Women of African Ancestry (OCWAA) consortium is a unique harmonized dataset of seven studies with over 1000 Black women and 3000 white women to better understand risk factors in Black women. 54 One such effort studied 10 EOC risk factors and found population risk attributable higher for Black women for all risk factors collectively including family history of breast cancer, BMI, OCP use, aspirin, and body powder. 55 Other studies found endometriosis, uterine fibroids but not early menarche to be relevant risks for Black patients with EOC. 56 , 57 Enriched datasets such as the OCWAA from diverse populations are critical to improve studies of disparities. A unique intervention for risk reduction and prevention is opportunistic salpingectomy, removal of fallopian tubes during benign gynecologic or obstetric surgery instead of ligation only. 58 This is recommended as a public health strategy for ovarian cancer prevention due to a paradigm shift in establishing the pathologic tubal origin of most EOC and recent studies showing decreased ovarian cancer diagnoses and cost effectiveness. 59 , 60 However, several authors have demonstrated that minority patients (Black, Hispanic and other non-white) are less likely to undergo salpingectomy. 61 , 62 A study of caesarean deliveries found Black patients were almost 50% less likely to have salpingectomy for sterilization. 61 Missed opportunities in prevention could heighten disparities if not intentionally and equitably adopted. High quality cancer care in ovarian cancer includes adequate cytoreductive and staging surgery, receipt of timely appropriate chemotherapy and genetic germline and tumor testing. In a large NCDB study, NCCN guideline non-adherence was found to be the single highest contributor to the disparity noted, explaining 36.4% of the 5 year overall survival disparity experienced by Black pateints. 63 , 64 Black ovarian cancer patients are less likely to receive full NCCN guideline recommended care than non-Hispanic white patients. 64 Several single institution retrospective studies at academic centers have not shown differences in treatment or survival by race or ethnicity as seen in larger datasets, suggesting that equity can be achieved in controlled settings but may be limited by bias of who can get care at these specialized centers. 65 , 66 Increased geographic distance from a high-volume hospital was also associated with less concordant care. Other patient-provider factors such as refusal of surgery, delays in diagnosis due to gaps or bias in provider education likely influence disparities but are harder to measure and mitigate. In a comprehensive meta-analysis, patients treated at low volume hospitals (five or fewer cases per year) or by low volume surgeons (< 1 case per month) were less likely to get appropriate guideline concordant care and had 8–16% increased mortality. 50 Patients living in rural areas were less likely to have surgery with a gynecologic oncologist or be treated in a high-volume center likely due to the skewed distribution of gynecologic oncologists favoring urban centers. 67 , 68 Rural patients having surgery with gynecologic oncology had increased appropriate surgery cytoreduction (OR 2.84; 95% CI 1.31–6.14) and chemotherapy (OR 4.22; 95% CI 1.82–9.78). 69 There is inherent tension between centralization of ovarian cancer care to improve access to high volume hospitals and surgeons with better outcomes and the burden this places on patients with travel limitations (e.g., rural, elderly or low income). Disparities in genetic testing and somatic testing affects care delivery for ovarian cancer and potential risk reduction of family members through cascade testing and preventive measures such as OCP use or risk reducing surgery. Germline pathogenic mutations are present in approximately 20 % of epithelial ovarian cancer including hereditary cancer syndromes related to BRCA1–2, BRIP1, RAD51D, PALB2, MLHI, MSH2, MSH6 and PMS2. Due the high rate of mutations and standard targeted treatment options such as PARP inhibitors, genetic testing is strongly recommended for all patients diagnosed with EOC regardless of age or family history, yet only 39% of patients are referred to counseling and 30% complete testing. 70 , 71 Testing uptake was even worse among minority patients (Black 25%, Asian 14% versus White 40%). Minority patients were referred more often only after a cancer diagnosis instead of high-risk family history reflecting potential provider bias. Those with no or government insurance also had less testing (23%, 26%) compared to those with commercial insurance (47%). Disparities extend to precision medicine testing, Gamble et al. 72 demonstrated that those with Medicaid were less likely to get germline or somatic tumor testing or other pathology testing than those with commercial insurance with the disparity widening over time. Policy and advocacy to promote biomarker coverage is critical to improve access. The Centers for Medicare & Medicaid Services (CMS) issued a coverage determination that increased access to biomarker testing and next-generation sequencing for Medicare (2020–22), but only five states had legislation supporting biomarker testing for Medicaid by 2022. 73 Failure to receive guideline care is multifactorial and likely a complex model of overall health care access that has been articulated by several authors. Montes et al in their analysis review measures of health care access dimensions to include: “affordability (ability to pay), availability (service type, quality, volume), accessibility (geographic location), accommodation, and acceptability (quality of patient-provider interaction, patient experience).” 64 An additional important framework ( Figure 5 ) considers proximal (individual, biologic), intermediate (social and physical environments) and distal structural factors to best explain causes of disparities and their interplay. 74

Uterine cancer encompasses endometrial cancer (EC) and less common uterine sarcomas and stromal malignancies. It is the fourth most common cancer diagnosed in U.S. women with 2023 estimates of over 66,000 new cases and over 13,000 deaths.. 6 Most patients with uterine cancer have low grade endometrioid histology, and early stage and have an overall good prognosis (over 80% 5-year survival) with surgical cure. These low-risk cancers are more associated with obesity, reproductive factors and are more hormonally driven in contrast to high-risk histology which have worse outcomes and significant disparity in race and age. Trends in rising incidence of uterine cancer in the U.S. are most pronounced in non-white patients. Increased annual percentage change (2007–2019) is higher for non-Hispanic minorities patients (Black-2.4%, Asian/Pacific Islander-2.5%, American Indian/Alaska Native- 2.5%) and Hispanic patients (2.9%) compared to non-Hispanic white (0.7%). 74 EC cases diagnosed those aged < 50 years (early onset) have also increased among Black, Hispanic, and non-Hispanic Asian Pacific Islander patients compared to NHW women. 75 Early onset EC tends to be hormonally driven and may be partially driven by trends in increasing obesity. Understanding and addressing these changing demographics particularly the rise in Hispanic women is a priority research area as the U.S. Hispanic population grows. Deaths due to uterine cancer are increasing for all groups but mortality rates remain most disparate for Black women 76 and are consistently close to double those of other racial and ethnic groups ( Figure 6 ). Recent SEER 5-Year Relative Survival Rates, 2013–2019, show Black women with significantly worse survival (63%) than non-Hispanic white women (84%), with even worse outcomes for Blacks over age 65 years (54.5%). 49 Black women are more likely to present at more advanced stages with worse survival at higher stage and older age ( Figure 7 ). A recent study which adjusted for varying rates of hysterectomy among populations found an overall increase in uterine cancer deaths (+1.7%) and a steeper rise in non-endometrioid high risk histology types (+2.7%). Non-endometrioid endometrial cancers including serous carcinomas, clear cell carcinomas and carcinosarcomas have a worse prognosis with a higher proportion of patients presenting in later stages, higher recurrence rates, and overall death rates. Approximately, 74% of all cases were shown to be endometrioid and contributed 40% of deaths, whereas the non-endometrioid types represented only 20% of cases but 45% of deaths. 77 Black women, compared to NHW women, are disproportionately affected by these high risk types (46.1% versus 21.6%) and are more likely to have an advanced disease stage (34.1% versus 19.8%), with worse outcomes after controlling for stage and treatment. 70 A SEER study (2000–2012) including all uterine sarcomas, another aggressive type, showed worse survival associated with age, Black race and advanced stage. 78 The differences in histology distribution introduces other potential gaps in care as patients require more complex treatment planning that integrates molecular classification with chemotherapy, targeted therapy, immunotherapy and/or radiation. Molecular profiling of endometrial cancer has rapidly changed the landscape for treatment as reflected in the new FIGO 2023 endometrial cancer staging incorporating tumor genomics based on prior TCGA categories. NCCN guidelines now reflect the need for more complex tumor testing such as microsatellite instability (MSI) and Her 2 neu testing; many are concerned about large scale equitable adoption of such precision medicine testing for all patients. There is no standard uterine cancer screening for asymptomatic patients. Timely diagnosis requires symptom recognition of postmenopausal or irregular premenopausal bleeding and appropriate workup with pelvic ultrasound and endometrial sampling. Disparities in stage at diagnosis and survival in Black women has been attributed to access variables (e.g., insurance, income), yet the picture is more complex and includes the efficacy of current diagnostic tools and guidelines, provider bias, and poor provider and patient knowledge. Lack of bleeding recognition and guideline concordant care prior to endometrial cancer diagnosis was associated with later stage at presentation for Black women. 79 Transvaginal ultrasound may actually underperform in Black women due to higher prevalence of fibroids distorting the endometrium and in high risk histology as lining thickness is not as predictive. False negatives can delay diagnosis if ultrasound is used as a triage tool instead of direct tissue sampling. Doll et al. 80 created a simulated cohort of Black and white women based on available survival data, ultrasound performance variables and histology; ultrasound missed four times more cases of EC in the Black cohort with a much lower sensitivity and positive predictive value. 80 Other authors demonstrated several delays in diagnosis in Black women compared to white women due to lack of or increased time before guideline-recommended diagnostic procedures, and more visits for abnormal bleeding before diagnosis was finalized. 81 Surgery with lymph node assessment is standard in early or localized endometrial cancer. Several studies have shown differences in surgery uptake contributes to the racial disparity in outcomes; Black women are less likely to have surgery or have less minimally invasive surgery. 82 , 83 In contrast to ovarian cancer, the association of high-volume hospitals or surgeon specialty to survival has not been as strong for uterine cancer. 84 Refusal of surgery has been another variable studied and found to be more common in older patients, Black patients, those without insurance or Medicaid, or those treated at a community hospital. 85 However, such association need further research as surgery refusal is likely influenced by multiple factors, other social determinants, patient-provider communication, trust, and/or provider bias. Patients with high-risk features including high grade histology, deeper myometrial invasion, or lymph node metastasis require adjuvant therapy with radiation and/or chemotherapy. Differences in guideline concordant care have been documented when comparing non-white to white patients. A study of over 19,000 women determined that non-white patients were less likely to get adjuvant radiation therapy (HR: Blacks 0.79, Hispanics/Asians 0.75). 86 Multivariate analysis also found lower income, non-academic hospital, and further distance from treatment center to be significantly associated with lack of radiation. Another analysis of NCCN guideline-concordant care found that Hispanic and non-Hispanic Black women were less likely to receive appropriate care even for high grade EC which in turn was associated with worse survival. 87 While adherence to quality standards provides potential strategies for intervention and mitigation by providers and health systems, several studies have shown that while quality treatment or other socioeconomic variables may improve survival, these factors alone do account for the persistent and growing disparities among minority women. 88 – 91 For example, a large study using NCDB data of over 270,000 Black and white women survival disparity was noted (5-year survival (58.6% vs 78.5%). 91 Estimated excess relative risk for survival was most attributable to histology in all women (~50%) and unexplained factors with slight differences in the proportional distribution by age (65 years or less versus older). Insurance was only a factor for younger patients accounting for 11.5% of the survival disparity in race. Progress towards health equity in in uterine cancer will require a multi-level approach that considers traditional gaps in diagnosis and treatment but also focuses specific attention on high-risk uterine cancer biology, early detection, development and delivery of more effective treatments. Increasing diversity in biospecimens and clinical trials will be central to such research efforts.

Nearly all cervical cancer can be prevented through identification and removal of pre-cancer caused by high-risk human papillomavirus (HPV). 2 Screening and early detection strategies have existed since the 1970s and led to a steady decline in U.S. incidence and mortality. The trend plateaued in the mid-2000s. The most recent data show declines in incidence among 15–29 year olds due to uptake of HPV vaccination by adolescents but worrisome increases in advanced stage diagnoses for White women in the Southern US region. 3 – 5 In 2023, an estimated 13,960 new cases of invasive cervical cancer will be diagnosed in the U.S. and about 4,310 patients will die of this preventable disease. 6 The cervical cancer burden is not equally distributed. 7 Race/ethnic minority groups experience higher incidence and/or mortality compared to non-Hispanic whites (NHWs). The cervical mortality rate is highest and 5-year relative survival is lowest for Black women. 6 , 8 Hispanic women have the highest incidence compared with other racial/ethnic groups (e.g., 32% higher than NHW women) but survival is more similar. 9 Native American/Alaskan Native populations have elevated incidence relative to NHW women (incidence rate ratio 1.64). 10 and 11 Besides race/ethnicity, rural residence, low socioeconomic status, and being uninsured are consistently associated with increased cervical cancer burden. 11 Rates of advanced stage cervical cancer are rising for white women in the Southern U.S. 5 Uninsured and publicly insured patients have a higher relative risk of late stage cervical cancer diagnosis than privately insured patients. 12 Disparities in age exist, as 20% are diagnosed over the age of 65 with worse survival outcomes. 13 Data is limited on whether these cases due to new HPV infections, inadequate screening history, or lack of appropriate follow up and whether current guidelines to stop screening after age 65 need adjustment. 14 Persistent disparities are attributed to poor access to and delivery gaps in the screening process. 15 In the U.S., adherence to guideline-recommended screening intervals declined from 86% in 2005 to 73% in 2021. 16 The COVID-19 pandemic exacerbated disparities in screening for minoritized and underinsured populations. From 2019 to 2021, screening adherence decreased less for NHW individuals than all other race/ethnic groups ( Table 1 ). These declines are problematic because over 50% of cases are in under-screened or never screened individuals. Cervical cancer is definitively linked to persistent HPV infection, with over 70% caused by HPV 16 and 18. 2 Development of new HPV-based technologies substantially changed clinical practice and guidelines in the U.S. ( Figure 2 ). Until the mid-2000s, the main prevention strategy was Papanicolaou (Pap) testing with triage to colposcopy for diagnosis and excisional treatment of pre-cancers. 17 Adolescent HPV vaccination was recommended in 2006. Technology to detect HPV nucleic acid was added to the US Preventive Services Task Force guidelines as an adjunct to Pap tests in 2012. 18 Currently, US guidelines recommend Pap testing every 3 years, primary HPV testing every 5 years, or co-testing (Pap and HPV) every 5 years for average-risk individuals irrespective of vaccination status. 14 , 19 Despite these new HPV-based technologies and guideline revisions, cervical cancer outcomes have not improved. To prevent cervical cancer, the entire process must be delivered in a timely fashion. Retrospective histories of cervical cancer cases in the U.S. have shown that 50–60% lacked a recent screening test; 15 , 20 , 21 in about 30% the test failed to detect an abnormality, and in 20% of cases, there was a failure to deliver diagnostic evaluation/treatment. U.S. data show problematic trends: cervical screening has stagnated at ~80% over the past 10 years and is substantially lower among uninsured (58%), low income (63%), less educated (57%), recent immigrants (56%), Hispanic (70%), Asian (68%), and Black (77%) populations. 22 The US Community Preventive Services Task Force (USCSPTF) recommends multi-component interventions to increase community demand for screening (e.g. reminders, incentives, media, one-on-one or group education), reduce structural barriers (e.g., patient navigators, community health workers, childcare assistance, alternative screening sites), and optimize provider delivery (e.g., provider assessment and feedback, incentives, and point of care reminders). 23 Data from the National Cancer Institute-funded Population-based Research to Optimize the Screening Process (PROSPR) Consortium shows significant variability in delivery of diagnostic evaluation. Across the three systems, 75.3% received a colposcopy within 12 months (site specific range 70.0 to 83.0%.) 24 Sites with more centralized processes to manage abnormal results (e.g., population health management or navigators) had higher proportions completing colposcopy. Given the complexity of guidelines, interventions by the healthcare system (e.g., information technology to support provider adherence to guidelines, address patients’ social determinants of health) are needed to improve quality and reduce variation. Less data exists in excisional procedures for diagnosis and treatment of precancer yet disparities in stage at diagnosis suggest delays in treatment. Once diagnosed with invasive cervical cancer, racial, age, insurance status and geographic disparities often reflect a failure to provide timely guideline concordant care. 25 A SEER-based analysis found mortality disparities and poorer outcomes in Black compared to white women could be attributed to insurance (18.6%) or treatment (47.2%). 26 , 27 Early-stage cervical cancer (tumors < 4 cm and limited to the cervix) can be treated and cured surgically with either simple hysterectomy or radical hysterectomy and lymphadenectomy/sentinel lymph node dissection depending on tumor size. Several studies of patterns of care show decreased rates of surgical treatment for Black women, older women, and those with Medicaid or no insurance. 28 , 29 As shown in Figure 3 , non-Hispanic Black women are more likely to have more advanced disease and require chemoradiation. Those lacking insurance, those of older age, and rural patients also present with higher stage disease. 5 , 11 , 29 Patients with locally advanced cervical cancer (LACC) require weekly chemotherapy and radiation with external beam pelvic radiation and intracavitary brachytherapy to achieve cure. 30 Treatment delay beyond 8 weeks is a quality metric and associated with decreased survival and local control of tumor spread. One study found Medicaid patients had significant delay from diagnosis to seeing radiation oncology compared to privately insured patients (Mean 76.9 v. 31.3 days, p = 0.03) and race and age were not significantly associated. 31 The financial, social and time burdens of the complex multimodal treatments are hardest on disadvantaged populations and introduce many possibilities for substandard care unless needs are addressed directly through navigation or improved care coordination. 32 Delivery of brachytherapy for LACC is another important quality metric with documented disparities by race (Blacks versus Whites). 32 – 35 Women over 60, and those with public insurance or uninsured, care in a non-academic center, or treatment in the Southern or Western U.S. regions also received less brachytherapy. 35 Disparities in access to advanced radiation modalities including intensity modulated radiation therapy (IMRT) lead to long term toxicities and poorer quality of life. 36 While quality care delivery of primary treatment is a modifiable intervention point, guideline concordant care does not completely mitigate disparities in survival; less traditionally measured factors such as stress, patient decision making, racism/bias, comorbidities, social determinants of health and social support should continue to be studied as mediators. 37 Recurrent cervical cancer is generally deemed incurable, but novel therapeutics including immunotherapy recently approved for cervical cancer have shown modest improvements in survival. Studies of access and utilization of biomarker-driven immunotherapy or other novel therapeutics are warranted to ensure equity in cervical cancer outcomes. 38 Achieving health equity in cervical cancer will require attention to primary and secondary prevention, and to equitable access and delivery of standard of care treatment for early and late-stage cervical cancer. Most cervical cancers arise in under-screened women; thus, the U.S. needs to invest in intervention programs to bring under-screened women into care. The most promising development is high risk HPV self-sampling as testing from patient-collected samples has equivalent sensitivity and specificity to clinician-performed HPV testing. 39 , 40 Several countries have incorporated HPV self-sampling 40 and approval by the US Food and Drug Administration is anticipated. In 2023, the Federal Cervical Cancer Collaborative 41 highlighted opportunities for federal, state, and local partners to advance cervical cancer control in collaboration with safety-net healthcare systems to better implement research into clinical practice to reach those at highest risk(e.g., racial/ethnic minority, low income, under/uninsured patients). Worldwide, cervical cancer is the fourth most common cancer and the fourth leading cause of cancer deaths in women, with an estimated 604,000 new cases and 342,000 deaths in 2020. 42 Approximately 90% of new cervical cancer cases and deaths occur in low- and middle-income countries (LMIC). Cervical cancer is the most commonly diagnosed cancer in women in 23 countries and the leading cause of cancer deaths in 36 countries located in Sub-Saharan Africa, Melanesia, South America, and South-Eastern Asia ( Figure 4 ). 43 Variance in mortality is attributable to poverty and the human development index (HDI); the latter indicating a country’s equitable implementation of HPV vaccination, cervical cancer screening, and treatment. Comparisons of LMIC to high-income countries (HIC) found differences in both screening (44% vs >60%, respectively) and HPV government vaccination programs (80%). Implementation of vaccination and screening must be adjusted to the local resources and healthcare setting capacity (e.g., visual inspection with acetic acid and “see and treat” programs in lower resource settings). Primary HPV testing via self-sample may overcome the barriers of transportation and hesitancy for pelvic exams. Several countries are offering this new modality to all eligible patients or to those not reached by traditional provider-based screening. 40 Treatment of pre-cancers and invasive disease continues to be challenging in LMIC. Cryotherapy is a common treatment option yet limited by availability of gas (e.g., nitrous oxide, carbon dioxide). 44 Loop electrosurgical excision procedure (LEEP) equipment is costly, requires electricity and more intense provider training. Limited availability of specially trained providers as well as radiation therapy, chemotherapy, and palliative care are other key targets. Programs to monitor quality of cervical cancer screening and treatment must be sustained as the COVID-19 pandemic illustrated vulnerability to disruption. 45 , 46 In 2020, the WHO called for the elimination of cervical cancer (i.e., ≤4 cases per 100,000 women worldwide) through: 47 Vaccinating 90% of girls by age 15; Screening 70% of women twice between the ages of 35 to 45 years; Treating at least 90% of precancers detected through screening. Modeling studies predict that if this goal is achieved, >74 million cervical cancer cases and >62 million deaths will be prevented over the next 100 years. 48

For cervical, ovarian, and uterine cancers, there are persistent racial and ethnic disparities in health outcomes with Black patients persistently experiencing the worst burden. Across all three gynecologic cancer types, research has become more nuanced in investigating how socioeconomic factors and social determinants of health contribute to disparities along the cancer care continuum. Timely delivery of screening and diagnostic evaluation is of paramount importance to eliminate cervical cancer disparities ( Figure 1 ). For ovarian and uterine cancer, due to the lack of screening options, it is critical that patients and healthcare providers recognize symptoms to ensure timely diagnostic evaluation; further, delivery of guideline-concordant cancer treatment, including tumor biomarker testing and somatic/germline genetic testing is important to promote cancer health equity ( Figure 1 ). Finally, the trends in high-risk uterine cancer histology, age of presentation, and disproportionate burden on non-Hispanic Blacks and Hispanics warrant additional investigation to identify mechanisms, modifiable factors and develop interventions along the continuum especially in potentially novel screening/early detection and treatment for high-risk disease.

Advances in the diagnosis and treatment of gynecologic cancers have not benefited all equally. Most disparities arise due to unequal delivery of cancer care across the continuum from primary prevention, detection, and diagnosis through treatment, and survivorship. 1 Understanding specific gaps in care at the health system, provider, and individual levels may offer insights for future interventions. Here, we highlighted how disparities manifest, drivers, and opportunities to achieve cancer health equity with respect to cervical, ovarian, and uterine cancers ( Figure 1 ).