Proton therapy for primary and recurrent HPV-related oropharyngeal cancer

The incidence of Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has risen over the past two decades, now accounting for 44-75 % of cases in Europe and the USA. This review synthesized data from PubMed, additional academic sources, and ongoing studies to summarize the potential role of proton therapy (PT) role in treating HPV-related OPSCC. In vitro studies support PT radiosensitization of HPV-positive cells and clinical experiences report high locoregional control (LRC) rates of 88.6-97 % with significantly reduced side effects such as xerostomia by 12.5 % and brain necrosis by 2.3 %, compared to intensity-modulated radiation therapy (IMRT). A randomized trial (NCT01893307) has also recently provided level 1 evidence showing that PT is non-inferior to IMRT for tumor control while reducing treatment-related toxicities, such as feeding tube dependence (28 % vs. 42 %, p = 0.019) and facilitating better work resumption outcomes (71 % vs. 52 % at 2 years). Despite the success of radiation de-escalation achieving LRC up to 95 %, recent trials indicate potential survival risks when standard treatments are modified. Failure pattern analysis showed that up to 70 % of locoregional recurrences occurred in-field, highlighting the potential role of PT in achieving LRC while minimizing toxicity. PT could also play a role in the reirradiation of recurrent OPSCC, with reported 1-year LRC rates of 71.8-80.8 %, 2-year LRC rates of 72.8-80.3 %, 1-year overall survival (OS) rates of 65.2-81.3 %, 2-year OS rates of 32.7-69 %, and late grade ≥2 toxicities of 11.9-36.3 %. Methodologies improving reRT approaches include dose/volume histogram comparisons, which recommended PT when it resulted in lower predicted toxicities.