The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck

Human papillomavirus (HPV)+ squamous cell carcinoma of the head and neck (SCCHN) is an entity distinct from that of HPV- SCCHN, possessing unique risk factors, etiology, epidemiology, biology, and clinical behavior. HPV+ and HPV- SCCHN are currently being treated similarly in the clinic. Future management of SCCHN should be optimized according to HPV status in order to reflect these important differences.Squamous cell carcinoma of the head and neck (SCCHN) was traditionally associated with smoking and alcohol use; however, human papillomavirus (HPV) infection has recently been implicated as a novel risk factor for oropharyngeal tumors. Furthermore, HPV-associated oropharyngeal carcinoma (OPC) appears to be a distinct entity with different epidemiology, biology, and clinical outcomes. Here, we comprehensively review the existing data regarding HPV status and prognostic or predictive outcomes in both the locoregionally advanced (LA) and recurrent/metastatic (RM) disease setting and discuss ongoing trials that may eventually impact the treatment of patients with HPV-positive (HPV+) SCCHN. A body of retrospective and prospective data established an association between HPV+ OPC and better survival, particularly for LA disease. Current data on RM disease are limited, but they also suggest prognostic significance for HPV. Better outcomes in HPV+ LA disease may allow for less aggressive treatment in the future, and several trials are evaluating deintensified regimens in patients with HPV+, LA OPC; it should be emphasized that deintensification strategies are appropriate only in a clinical research setting and only for selected subgroups of HPV+ patients. In addition, HPV-targeted strategies, such as vaccines, are currently undergoing clinical evaluation. On the other hand, the prognostic impact of HPV in RM disease requires further validation before any modifications in treatment can be made. Likewise, the predictive significance of HPV status in both disease settings remains to be defined. NCT00226239, NCT00301028, NCT00387127, NCT00410826, NCT00503997, NCT00514943, NCT00544414, NCT00768664, NCT00939627, NCT01084083, NCT01302834, NCT01687413, NCT01706939.