Should patients with HPV-positive or negative tumors be treated differently?

The striking rise in the incidence of HPV-related oropharyngeal squamous cell carcinomas and their improved prognosis compared to classical oropharyngeal cancer raises the question as to whether this subset of patients could benefit from less aggressive treatment without compromising efficacy. To achieve that goal, it is critically important to advance our understanding of the behavior of HPV-positive tumors. It is necessary to identify relevant clinical risk factors and to refine the current staging system. Several clinical trials studying various deintensification strategies are currently underway. This review presents some of the most valuable evidence in this regard in an attempt to encourage further exploration of risk stratification and risk-based therapy for patients with oropharyngeal cancer.