Human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The most recent (8th) edition of the Union for International Cancer Control/American Joint Committee on Cancer staging system separates HPV-OPSCC from its HPV-negative counterpart to account for the improved prognosis seen in the former. Indeed, owing to its improved prognosis and greater prevalence in younger individuals, numerous ongoing trials are examining the potential for treatment deintensification as a means to improve quality of life while maintaining acceptable survival outcomes. Owing to the distinct biology of HPV-OPSCCs, targeted therapies and immunotherapies have become an area of particular interest. Importantly, OPSCC is often detected at an advanced stage, highlighting the need for diagnostic biomarkers to aid in earlier detection. In this review, we highlight important advances in the epidemiology, pathology, diagnosis, and clinical management of HPV-OPSCC and underscore the need for a progressive understanding of the molecular basis of this disease toward early detection and precision care.
Keywords: head and neck squamous cell carcinoma; human papillomavirus; immune escape; nonkeratinizing; oropharynx.