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.

Contemporary review.

Published journal articles identified through PubMed and conference proceedings were reviewed.

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.

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 HPV‐associated oropharyngeal carcinoma may lead to novel therapeutics for patients with carcinogen‐associated carcinomas. Laryngoscope, 2010