Human papillomavirus-associated oropharynx cancer (HPV-OPC): treatment options.

opinion statementHuman papillomavirus-associated oropharynx cancer (HPV-OPC) is growing in incidence and has distinct clinical, pathologic, molecular, and epidemiologic features. However, the management of HPV-OPC does not presently differ from HPV-negative OPC based on the current evidence and requires complex multidisciplinary approaches. The superior prognosis of HPV-OPC and the toxicities of current multimodality treatment in a young population serve as the impetus to evaluate de-intensification treatment regimens aimed at reducing toxicity while maintaining therapeutic efficacy. Clinical trials are underway to evaluate reduced doses of radiation or less toxic systemic therapy regimens in HPV-OPC. Minimally invasive surgical approaches in the HPV-OPC population with early tumor stage also are being investigated. De-intensification strategies should only be employed in the context of clinical trials, and HPV-OPC patients should be offered clinical trials' participation. Appropriate patient selection is critical to the development of de-intensification regimens, and this requires greater understanding of risk factors within the HPV-OPC population, HPV-OPC biology, and how HPV modulates response to specific therapies. Smoking history and bulky nodal disease have been shown to impact negatively the favorable prognosis of HPV association. Validated biomarkers within the HPV-OPC population are lacking, although alterations in the PI3K pathway and markers of immune response may emerge as important considerations in the future. Novel therapeutic strategies are desperately needed particularly for HPV-OPC patients who fail definitive therapy, and select patients with recurrent or metastatic disease may benefit from aggressive approaches.