Screening and Prevention for High-Grade Serous Carcinoma of the Ovary Based on Carcinogenesis-Fallopian Tube- and Ovarian-Derived Tumors and Incessant Retrograde Bleeding.

High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian carcinoma. Many HGSCs are now believed to originate in the fallopian tube epithelium; ovarian surface epithelium is another possible origin. Thus, current screening methods, i.e., ultrasonography and serum CA-125 measurements, have a limitation in their early detection. Recently, circulating biomarkers, such as tumor DNA, autoantibody, and microRNA, have been investigated to detect HGSCs. As cancer cells in the fallopian tube flow into the endometrial cavity, the detection of exfoliated cells, tumor DNA, and proteome from samples obtained from the endometrial cavity or the cervix may be useful. The risk of ovarian serous carcinoma is affected by the use of oral contraceptive and menopausal hormone therapy (MHT). MHT regimens causing endometrial bleeding increase serous carcinoma risk, hence, incessant retrograde bleeding from the endometrial cavity into the Douglas pouch appears to play an important role in high-grade serous carcinogenesis. In this review, we provide an overview of current and novel screening methods and prevention approaches for ovarian and fallopian tube HGSC.