Human Papillomavirus and Oropharynx Cancer: Biology, Detection and Clinical Implications

Objectives: To review evidence for the role of human papillomavirus (HPV) in the etiology of oropharyngeal cancers, methods of viral detection, and the resulting clinical implications. Study Design: Contemporary review. Methods: Published journal articles identified through PubMed and conference proceedings were reviewed. Results: HPV-associated squamous cell carcinomas represent a distinct disease entity from carcinogen-associated squamous cell carcinomas. HPV oncoproteins lead to mucosal cell transformation through well-defined mechanisms. Different methods of detecting HPV exist with variable levels of sensitivity and specificity for biologically active virus. Although virus is detected in a number of head and neck subsites, studies demonstrate improved outcomes in HPV-associated carcinoma of the oropharynx only. The cell cycle regulatory protein p16 is upregulated by biologically active HPV and serves as a biomarker of improved response to therapy. Conclusions: HPV-associated squamous cell carcinoma of the oropharynx is a biologically distinct entity from carcinogen-associated carcinoma. Understanding the molecular mechanisms behind the improved outcomes in patients with H2V-associated oropharyngeal carcinoma may lead to novel therapeutics for patients with carcinogen-associated carcinomas.