Evolving Treatment Paradigms for HPV-Related Oropharynx Cancer

It is now well-established that human papillomavirus (HPV)-associated squamous cell carcinoma, which comprises an increasing proportion of all oropharyngeal cancers, represents a unique entity with distinct clinical and molecular characteristics. Data also has emerged demonstrating that patients with HPVpositive head and neck cancer have an improved prognosis compared to their HPV-negative counterparts, with several series showing that patients with HPV-related tumors arising from the oropharynx have at least half the risk of death. However, these studies have been complicated by such factors as the limited quality of data, small sample sizes, as well as the variability in treatment, inclusion criteria, and follow-up. Although the exact reason for the improved survival among HPV-positive patients is unclear, many investigators have proposed that HPV-related head and neck cancer is more sensitive to the effects of radiation therapy than HPVnegative tumors arising in the setting of traditional environmental exposures. Despite the attractiveness of this hypothesis, the data focusing on possible de-intensification approaches remains preliminary, and treatment paradigms will likely continue to evolve as findings from innovative clinical trials yield answers to many provocative questions.