Evolving role of human papillomavirus as a clinically significant biomarker in head and neck squamous cell carcinoma.

: The majority of squamous cell carcinoma (SCC) of the oropharynx, one of the sites within the head and neck region, is now associated with high-risk human papillomavirus (HPV) in North America. Several modalities are available to determine the HPV status, however, the understanding of each assay in its application and limitations is essential for accurate interpretation and appropriate utilization of results in management of these patients. : This expert review will cover the role of HPV in head and neck squamous cell carcinoma (HNSCC), indications for HPV testing, HPV detection methods in tumors, saliva and serum, and exploiting HPV status as a prognostic biomarker of clinical outcome in HNSCC. : The HPV status is the most significant diagnostic and prognostic biomarker in HNSCC, specifically in the oropharynx. Research underway is currently delineating the role of HPV and p16 testing in non-oropharyngeal sites. While the feasibility of non-invasive serum and saliva testing for HPV detection has been established, the clinical application of these assays is still evolving.