Controversies in Treatment Deintensification of Human Papillomavirus–Associated Oropharyngeal Carcinomas: Should We, How Should We, and for Whom?

It has been little more than a decade since the recognition of the epidemiology, distinct molecular biology, and profile of risk factors, patient demographics, and tumor characteristics of human papillomavirus (HPV) ‐associated oropharyngeal squamous cell carcinoma (OPSCC). 1-3 From prospective and retrospective studies, we know that patients with locally advanced, stage III/IV, HPV-associated OPSCC who are treated with standard cisplatin-based concurrent chemoradiotherapy have significantly better overall survival and reduced risk of recurrence compared with patients with HPV-negative OPSCC. 4-6 More than 80% will likely be cured of their cancer. That said, it is also evident that a subset of patients demonstrate an aggressive phenotype with the development of distant spread and death as a result of their cancer. Given that the typical patient with HPV-associated OPSCC is younger (age 40 to 60 years) and without major comorbidities, increasing discussion has been focused on deintensification of treatmentinthehopesofminimizingtreatment-relatedmorbidity without compromising the current cure rates. In particular, attention has been focused on reducing the morbidity of severe late swallowing complications that result in the need for enteral nutritional support, because this has been shown to substantially affect patient quality of life. 7 Historically, typical rates of long-term gastrostomy-tube dependence were reported to be 15% to 20%. 8,9 However, with advances in radiationtechnology(suchasintensity-modulatedradiationtherapy), target delineation has become more complex, with steeper dose gradients and shifting of dose away from organs at risk, such that the current frequency of severe swallowing dysfunction needs to be reestablished. Nonetheless, maximizing quality of life by not overtreating patients is a uniformly supported goal. Deintensificationstrategieshavetodatebeenbasedonanunder