De-escalated radiation for human papillomavirus virus-related oropharyngeal cancer: evolving paradigms and future strategies

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma has increased dramatically in recent years reaching epidemic-like proportions. Data has emerged not only showing that these cancers are a unique entity with distinct molecular characteristics but that they also have a significantly improved prognosis as a result of their exquisite radiosensitivity compared to their HPV-negative counterparts. This, it has been increasingly suggested that these tumors can be targeted with de-escalated approaches using reduced doses of radiation. The overriding goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the incidence of both short- and long-term toxicity. Although the exact reason for the improved radiosensitivity of HPV-positive oropharyngeal carcinoma is unclear, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain the high rates of cure and preserve quality of life for appropriately selected patients with this disease. However, these studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in treatment, inclusion criteria, and follow-up. As the data continues to mature on de-escalation, it is unquestionable that treatment paradigms for this disease will evolve. The ongoing quest to define a standard regimen comprises the subject of this review.