Advanced oropharyngeal squamous cell carcinoma: Pathogenesis, treatment, and novel therapeutic approaches

Oropharyngeal cancer accounts for approximately 2.8% of newly cancer cases. Although classically a tobacco related disease, most cases today are related to infection with human papilloma virus (HPV) and present with locally advanced tumors. HPV related tumors have been recognized as a molecularly distinct entity with higher response rates to therapy, lower rates of relapse, and improved overall survival. Treatment of oropharyngeal cancer entails a multi-disciplinary approach with concomitant chemoradiation. The role of induction chemotherapy in locally advanced tumors continues to be controversial however large studies have demonstrated no difference in survival or time to treatment failure. Surgical approaches may be employed with low volume oropharyngeal cancers and with development new endoscopic tools, more tumors are able to be resected via an endoscopic approach. Given advances in the understanding of HPV related oropharyngeal cancer, ongoing research is looking at ways to minimize toxicities via de-intensification of therapy. Unfortunately, some patients develop recurrent or metastatic disease. Novel therapeutics are currently being investigated for this patient population including immunotherapeutics. This review discusses the current understanding of the pathogenesis of oropharyngeal cancer and treatment. We also discuss emerging areas of research as it pertains to de-intensification as well novel therapeutics for the management of metastatic disease.