Novel Approach for Therapeutics of Cervical Cancer Based on HPV-Associated Carcinogenesis at the Cervix

Abstract

High-risk human papillomavirus (HPV) is associated with the carcinogenesis of not only cervical cancer but anal, penile, vulvar, vaginal, and oropharyngeal cancers. Although molecular biological mechanisms of high-risk HPV (HR-HPV)-associated carcinogenesis is well studied, it remains unclarified why cervical cancer is the most common among these HPV-associated cancers. Two major causes are that the cervix is a susceptible site to viral infection because of its immune deficiency to protect allogenic sperm in reproductive function and that the squamocolumnar junction (SCJ) where cervical neoplastic diseases develop is composed of tissue stem cells with self-renewal and pluripotency. This specific environment of the cervix allows HPVs to be persistently infected into the cervical epithelial cells, followed by the immortalization of the HPV-infected cells. We here focused on the carcinogenesis specific to the cervix as novel therapeutic strategies for cervical cancer, targeting cancer stem cells and mucosal immunotherapy.