Advances and Challenges in Treatment De-Intensification of HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Purpose of Review: Management paradigms for oropharyngeal carcinoma (OPC) have been rapidly evolving due to the recognition that cancers associated with the human papillomavirus (HPV) have a favorable prognosis. This is especially the case with radiation therapy as a principal curative modality, as it is associated with a number of significant treatment complications due to the anatomic density of the head and neck and the importance of the oropharyngeal organs in swallow function. This has consequently raised major questions as to whether management can be fundamentally de-intensified in terms of dose and volume, and thereby reduce injury to the surrounding normal tissue. Recent Findings: Several phase I/II clinical trials have supported the hypothesis that early stage HPV-OPC can be effectively treated with de-intensified therapies from an oncologic perspective, although there remain many unanswered questions regarding the optimal de-escalation strategy from a toxicity perspective. Confounding these efforts remains our inability to quantify normal tissue injury and its relationship to swallow function. To date, existing tools largely quantify the degree of swallow injury with varying degrees of reproducibility and granularity. Analyses of the relationship between radiation dose and swallow outcomes have also typically been limited to the dose delivered to isolated normal structures and have not considered spatial radiation dose to the complex “systems” of organs that govern swallow function. Summary: Treatment de-intensification for HPV-associated OPC represents a rapidly advancing field where early studies suggest that oncologic efficacy for early stage cancers may not be compromised with lower radiation dose and minimally invasive surgical techniques. Generalizing this conclusion remains limited by the number of patients evaluated in clinical trials. The ability to determine if these efforts are reducing normal tissue injury and swallow function is also limited by the existing instruments used to measure injury.