p16 expression as a surrogate marker for HPV‐related oropharyngeal carcinoma: A guide for interpretative relevance and consistency

Recent studies of oropharyngeal carcinoma have reported remarkable correlation between integrated human papillomavirus (HPV) viral detection and p16 protein overexpression in tumor cells. These findings led to calls for the substitution of p16 expression for the more demanding HPV testing in clinical practice. The rationale for such practice is largely driven by the simplicity, low cost, and the feasibility of the immunohistochemical (IHC) analysis. There are, however, several caveats that need to be fully considered. These include the subjective nature of IHC evaluation, the variable mechanisms of p16 expression in head and neck squamous cell carcinoma, and the lack of scoring and interpretive criteria. This perspective addresses the conceptual and practical issues associated with the p16 expression analysis and provides a broad outline for its application and evaluation in patients with oropharyngeal carcinoma.