The DETECT Study: Discovery and Evaluation of Testing for Endometrial and Ovarian Cancer in Tampons

BACKGROUND:

Endometrial cancer is the most common and second deadliest gynecological cancer in women in the United States, with over 65,000 new cases and 12,000 deaths expected to occur in 2022. Unlike most cancers, endometrial cancer incidence and mortality are increasing, due primarily to rising rates of aggressive subtypes of endometrial cancer (non-endometroid tumors, i.e., serous or clear cell histology), which are more common in Black or African American (henceforth referred to as "Black") women. In addition to being more clinically aggressive, these non-endometrioid tumors are thought to have different risk factor profiles, precursor lesions, and molecular features than the more common and less aggressive endometrioid subtypes.

The same morphologic subtypes (serous and endometrioid) with similar molecular profiles are also found in ovarian cancers, which share many risk factors with endometrial cancers.

Racial disparities in endometrial cancer incidence and mortality have been reported, with Black women experiencing more rapid increases in incidence, as well as a higher burden of endometrial cancer mortality compared to other racial/ethnic groups. The underlying basis for these disparities is likely multifactorial, involving biological differences, as well as clinical factors related to access to care, delayed diagnosis, and differences in treatment and surgical management.

If identified early, endometrial cancer can be highly curable; however, the earliest stages may be asymptomatic, and clinical symptoms are often missed. Combining sensitive molecular testing approaches with non-invasive sampling techniques may to lead to the development of novel endometrial cancer early detection approaches with the potential to overcome disparities in access to care and time to diagnosis and treatment.

In contrast to endometrial cancer, ovarian cancer is typically detected at advanced stages with poor survival since symptoms manifest only late in the disease process and are very unspecific. Racial disparities in ovarian cancer incidence and mortality are also much less pronounced. Racial disparities can manifest particularly when screening, symptom appraisal and early detection, and effective treatment interventions have important roles in determining outcomes of cancers. Contrasting ovarian and endometrial cancers, which have similar risk factors and biologic underpinnings, but very different clinical courses, can further help to elucidate the role of behavioral and healthcare system-related causes of endometrial cancer disparities.

The investigators and others have recently shown that lower genital tract sampling approaches such as vaginal tampons, offer an acceptable and feasible method for identifying molecular markers with high sensitivity and specificity for endometrial and ovarian cancers. Importantly, these proof-of-principle studies have been conducted in predominantly non-Hispanic white (white) populations, and studies of molecular markers for endometrial and ovarian cancer, including those involving vaginal tampons, are lacking in black women.

OBJECTIVES:

The primary objectives of this study are to Aim 1) Characterize racial differences in risk factor associations with endometrial and ovarian cancers by histologic subtype; Aim 2) Assess associations of care delays related to symptom appraisal with endometrial cancer diagnosis and whether delays are associated with tumor characteristics; Aim 3) Evaluate determinants of acceptability and feasibility of vaginal tampon sampling; 4) Evaluate the performance of molecular biomarkers for endometrial cancer detection in paired tampon-collected and tissue specimens, overall and by race and histologic subtype; 5)Evaluate clinical, molecular, and epidemiological factors associated with endometrial cancer recurrence and survival overall and by race.

The secondary objective of this study are to: 1) Compare findings in ovarian cancer cases and controls to findings in endometrial cancer cases and controls as described in primary aims 1-5. For each specific aim above, ovarian cancer will represent an important comparison to (1) understand novel risk factor and biological associations by comparing histologic subtypes across cancer sites, (2+3) to better understand the role of behavioral and healthcare system-related causes of endometrial cancer disparities, (4) to evaluate biomarkers for gynecological cancer detection, and (5) to study factors associated with prognosis and outcomes; 2) Support discovery and validation efforts of liquid biopsy markers and artificial intelligence approaches for prognostic applications.

The goal of this study is to evaluate the acceptability, feasibility, and clinical performance of vaginal tampon sampling for molecular testing of endometrial cancer early detection biomarkers in a racially diverse clinical population.

ELIGIBILITY:

Eligible participants will include people with a uterus (hereafter referred to as "women") aged ≥18 years undergoing clinically-indicated hysterectomy and/or bilateral salpingo-oophorectomy for endometrial or ovarian cancer, cancer precursors, or benign conditions at the University of Alabama's Division of Gynecologic Oncology and Department of Gynecology.

DESIGN:

This is a case-control study with prospective follow-up of the electronic health record for up to 5 years. Cases will be defined as women with histologically-confirmed endometrial or ovarian cancer or cancer precursors diagnosed at hysterectomy/oophorectomy. Controls will have no histologic evidence of endometrial or ovarian cancer or cancer precursors diagnosed at hysterectomy/oophorectomy.

The primary endpoints of this study will be: 1) Associations of clinical and epidemiologic factors with odds of endometrial and ovarian cancer by race and subtype; 2) Associations of factors related to symptom appraisal and care delay with tumor characteristics, overall and by race; 3) The acceptability and feasibility of vaginal tampon sampling, assessed by evaluating 10 items from a brief survey regarding tampon sampling and the DNA yield from the vaginal tampon, respectively; 4) The prevalence, sensitivity, and specificity of endometrial and ovarian cancer molecular biomarkers in tampon and tissue samples in cases and controls; 5) Associations of clinical, molecular, and epidemiologic predictors of endometrial and ovarian cancer recurrence and survival.