In this Fast Track application, a path to commercialization will be pursued for a breakthrough genetic cytology test capable of detecting both ovarian and endometrial cancer from routinely collected Pap specimens. In deference to the notable success of the Pap test in reducing deaths due to cervical cancer, and in reference to the core enabling genetic sequencing technology, this new test has been named PapGene. The PapGene test detects ovarian and endometrial cancers by applying newly affordable sequencing technology to Pap specimens; specimens that are safely and routinely collected from 50 million women each year in the United States. The PapGene test is a genetic cytology assay that achieves sensitivity and specificity through identifying DNA mutations causative of cancer from routinely collected clinical specimens. With traditional cytology (e.g., Pap testing), cells are subjectively analyzed for abnormal cell morphology through visualization by light microscopy. The PapGene test allows cells to be analyzed objectively with a massively parallel sequencing-based assay. The test uses a proprietary sequencing error-reducing strategy to accommodate the relatively low proportions of cancer-derived DNA that may exist in clinical specimens. In Phase I, this study will determine the accuracy, precision, analytical sensitivity, analytical specificity, reportable range, and reference range of the PapGene genetic cytology assay (Aim 1). A retrospective study will also be completed on previously-collected samples to demonstrate the clinical validity of the PapGene assay (Aim 2). In Phase II, this study will demonstrate clinical utility of the PapGene test for women at high risk for ovarian and endometrial cancer. A prospective study will be completed by applying the PapGene assay to two prospective cohorts - patients with postmenopausal bleeding undergoing endometrial biopsy and patients with a germline BRCA1 or BRCA2 undergoing Risk Reducing Salpingo-Oophorectomy (RRSO) (Aim 3). Regulatory approval for the PapGene test will be pursued by establishing a CLIA-certified laboratory for high-complexity testing to allow for commercial use of a Laboratory Developed Test (LDT). Discussions with the FDA will be started regarding premarket clearance and approval for the PapGene test to allow for more widely distributed use (Aim 4).
This research will advance the development of a clinically useful genetic cytology assay for the detection of early stage endometrial and ovarian cancer. Future benefits include the potential availability of a screening test to detect ovarian and endometrial cancer while still surgically curable.