Future treatment directions for HPV-associated head and neck cancer based on radiobiological rationale and current clinical evidence

•HPV status is a new variable in the equation of head and neck cancer treatment.•HPV+ oropharyngeal cancer exhibits different biological behaviour from HPV− tumours.•HPV+ oropharyngeal cancer is more responsive to therapy.•Dose de-escalation would be beneficial in reducing toxicity.•Robust biomarkers are needed for patient stratification.

A relatively new entity of head and neck squamous cell carcinoma located in the oropharynx and associated to the human papillomavirus (HPV) is on the rise. This cancer represents a distinct entity from the non-HPV tumours, holds different biological characteristics and responds differently to treatment. An outcome analysis of locoregionally-advanced oropharyngeal versus non-oropharyngeal cancers treated with chemo-radiotherapy revealed a statistically significant improvement for oropharyngeal cancers, which are thought to be due to their HPV-association. Consequently, more attention is paid to HPV-related head and neck cancers, given that HPV status serves as prognostic marker in oropharyngeal cancer patients. Yet, HPV positivity is a simplistic approach for risk stratification, thus more robust biomarkers are needed to fulfil this task.Despite differences in clinical response, HPV-related oral cancers undergo similar therapy to their non-HPV counterparts. This review discusses future treatment directions for HPV-related oropharyngeal cancers based on radiobiological rationale and current clinical evidence.