HPV-related squamous cell carcinoma of the head and neck: An update on testing in routine pathology practice

Oropharyngeal squamous cell carcinoma caused by high-risk types of human papillomavirus (HPV) is now a well-recognized tumor entity whose incidence is on the rise. Most HPV-related oropharyngeal squamous cell carcinomas have a distinct histomorphology, and most patients fit a typical clinical profile. Importantly, HPV-related oropharyngeal carcinoma patients overall have significantly improved outcomes when compared to their HPV-negative counterparts, and the differences in tumor biology may soon lead to modifications in how they are treated. While high-risk HPV can be detected in a significant minority of head and neck squamous cell carcinomas across anatomic subsites in the head and neck, it has become clear in recent years that the biologically and clinically favorable features are limited to tumors that harbor transcriptionally active, high-risk HPV, something that occurs predominantly (but certainly not exclusively) in the oropharynx. It is now acknowledged that detecting transcriptionally active, high-risk HPV is a necessity in routine clinical practice, but there is considerable confusion among pathologists and clinicians alike about the subsites and settings in which HPV testing should be performed. Compounding this lack of clarity is the fact that there are multiple HPV testing options available, but currently there is no clear consensus on which test or combination of tests is optimal for routine diagnostic use. This review serves as an update for practicing pathologists on the current status of HPV (and surrogate marker) testing in head and neck cancers.