New insights into the pathogenesis of ovarian carcinoma: time to rethink ovarian cancer screening.

Recent discoveries about the pathogenesis of ovarian cancer have suggested that it can no longer be thought of as a single entity, but that the histologically defined ovarian cancer subtypes are different diseases, with different precursor lesions and distinct biomarker expression profiles. Most serous carcinomas probably arise from the fallopian tube. Clear cell and endometrioid carcinomas are associated with endometriosis and likely originate from ectopic endometrium. The focus of large ovarian cancer screening trials has been detection of macroscopic ovarian abnormalities by ultrasonography and detection of serum biomarkers associated with the most common (serous) subtype of ovarian cancer. The only completed and phase three randomized controlled trial failed to achieve the objective of reducing ovarian cancer mortality and was not able to demonstrate a stage migration effect of the screening. Future screening strategies have to incorporate our growing understanding of each subtype of pelvic (ovarian or fallopian tube) cancer, its organ of origin, and disease-specific biomarkers. We review how our current understanding of pathogenesis should prompt a reexamination of data from ovarian cancer screening studies and discuss potential designs for future screening strategies.