Project Funding Details

The high lethality of ovarian cancer and abnormal p53 (p53abn) endometrial cancer is related to their late diagnosis. Early detection of these gynaecological cancers would significantly increase patients' survival. The recent understanding of the natural history and molecular biology of these tumours has considerably improved, rendering an entirely novel approach to their early detection feasible. The hypothesis underlying this project is that DNA from tumour cells in the ovarian surface, the Fallopian tube lining, or the endometrial tissue shed into the luminal space and reach the cervical canal at an initial phase of tumour development. Thus, early diagnosis could be achieved through molecular analysis of cervical smear samples, that are currently routinely used as a screening method for the early detection of cervical cancer. Our previously published results have shown the feasibility of this approach. Through a proof-of-principle study, we have demonstrated that tumour genomic aberrations can be detected in DNA from cervical smears many years prior to the diagnosis of high-grade serous ovarian cancer. This proposal aims to assess the diagnostic performance of a new test (EVA test) for early diagnosis of high-grade serous ovarian cancer - using a much larger number of cases than previously used in the proof-of-principle study - of low-grade serous, clear cell, endometrioid ovarian cancers, and of abnormal p53 endometrial cancer. Further aims are to investigate whether any demographic/clinical factors influence the diagnostic performance of the EVA test, and to evaluate the performance of the EVA test longitudinally, i.e. at different time intervals before diagnosis. A retrospective clinical study engaging 23 Italian clinical centres will be organized. We plan to recruit at least 320 women with ovarian cancer, 200 women with endometrial cancer and 400 healthy women (controls). For each woman, archival cervical smears, primary tumour biopsies and some demographic/clinical data will be collected. DNA will be purified from all specimens and genomic alterations will be measured. A statistical analysis will elaborate the output and calculate the performance measures (sensitivity, specificity, accuracy) of the EVA test for each ovarian cancer histotype and p53abn endometrial cancer. We expect to confirm the results previously obtained in high-grade serous ovarian cancer in a large population of women, thus allowing a more precise definition of the performance measures of the EVA test. We expect to assess its diagnostic accuracy also in other ovarian cancer histotypes and p53abn endometrial cancer. The EVA test could be included in the universally used screening programs for cervical cancer diagnosis in the overall female population. As to the long-term perspective, the application of the EVA test will help anticipate the diagnosis of ovarian cancer and p53abn endothelial cancer, thus increasing their curability.