Genome-wide methylation and proteomic analysis of uterine lavage and cervical swab for early detection of ovarian cancer

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Project Summary/Abstract – Overall A three-decade research program developing, optimizing, and testing an annual blood-based test for the early detection of ovarian cancer in normal risk postmenopausal women failed to show a cancer-specific mortality reduction. The likely fundamental reason for the failure is the short window of opportunity provided by a blood-based signal. The proposed BCC will seek to identify an alternative biospecimen for the source of signal which has a much greater window of time for detection in early-stage disease so that an annual testing frequency will have a high likelihood of detecting ovarian cancer during its curable stages. Due to the direct connection of the uterus to the fallopian tube, where the cell of origin resides, a uterine lavage will likely contain the earliest biological signals of the presence of ovarian cancer. Identifying a minimal ovarian cancer signal amongst a much greater background of uterine epithelium cells and cellular material requires a very sensitive test. Our BCC will build on a recently developed innovative genome-wide methylation test and combine it with a sensitive antibody based proteomic test. Having optimized the combined test to detect a signal in uterine lavage, the BCC will determine its sensitivity in Pap smears. The BCC will optimize the combined test on training uterine lavage samples, validate the test on independent validation cohort of uterine lavage samples, and assess its performance in Pap smear samples. If the optimized test is sensitive in Pap smears, then the overall goal of a clinically acceptable and readily performed test (Pap smear) conducted at a feasible frequency of every 12 months will be a crucial step towards an annual test for the early detection of ovarian cancer in normal risk postmenopausal women, the population in which 80% of ovarian cancers occur. The long-term goal is an early detection program resulting in a significant reduction in ovarian cancer mortality. The intended use of the test developed by the BCC will be as a clinical decision-support tool for screening normal risk postmenopausal women for early detection of ovarian cancer. Such a test will fill an unmet health gap since there is currently no early detection test for ovarian cancer.