HPV as a marker for molecular characterization in head and neck oncology: Looking for a standardization of clinical use and of detection method(s) in clinical practice

Background: A consensus about the most appropriate diagnostic method(s) for head and neck human papillomavirus (HPV)‐induced carcinogenesis is still lacking because most of the commercially available assays have been designed for the cervix. Methods: This article summarizes current data and trends concerning HPV diagnostic strategies in oropharyngeal squamous cell carcinoma (OPSCC). Six main approaches are described. Results: The diagnostic gold standard for HPV‐related OPSCC, focusing on E6/E7 mRNA detection, requires fresh samples. Because most frequently available samples are formalin‐fixed paraffin‐embedded (FFPE), the pros and cons of the different approaches were analyzed. Conclusions: In the FFPE samples, the immunohistochemistry of p16, which is considered appropriate to assess HPV‐driven carcinogenesis in OPSCC according to the 8th American Joint Committee on Cancer TNM classification, may not be specific enough to become the diagnostic standard in the perspective of treatment deintensification. p16 may play a safer role in combination with another highly sensible assay. Other promising approaches are based on DNA detection through real‐time polymerase chain reaction and RNAscope.