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.