Exploiting HPV-Induced Carcinogenesis for a Rational Drug Development in Cervical Cancer

Abstract

Cervical carcinomas are almost universally associated with high-risk human papillomavirus (HPV) infections, and are a leading cause of cancer death in women worldwide. Since the late 1990s, when a spate of studies reported the benefit of cisplatin-based chemotherapy, there had been a dearth of clinical trials in cervical cancer (CC). More effective therapies in locally advanced and recurrent or metastatic CC are an urgent clinical need. In the era of molecular oncology one should look beyond conventional chemoradiation and chemotherapy for locally advanced and advanced CC. The fact that the initiating oncogenic insult, infection with a high-risk HPV and viral oncoprotein expression is common to almost all CC offers unique opportunities for disease control. Diverse biologic pathways with an implication in the development and progression of CC are being explored. For the first time, increase in overall survival has recently been obtained for advanced CC patients with a target drug, the antiangiogenic agent bevacizumab, and durable complete responses after HPV-targeted adoptive T cell therapy in metastatic CC patients were achieved. In this review, we will summarize molecular aspects of HPV infection focusing on potential targets to stop the carcinogenic process, present updated drug development data, and discuss challenges and prospects for the future.