Can we safely de-escalate HPV+ oropharyngeal cancers? - A review of current practices and novel approaches.

Oropharyngeal carcinomas linked to high-risk types of human papillomavirus (HPV⁺OPC) as a distinct tumor entity, have a better prognosis than HPV^-OPC. Current treatment approaches do not differentiate between HPV-positive and negative disease, but ongoing studies are exploring de-escalation strategies, aiming to reduce therapy-related morbidity and improve patient quality of life, particularly focusing on reducing late effects from radiotherapy.We performed a literature search for both published and ongoing clinical trials and critically discussed the presented concepts and results. Those include reduction in radiotherapy dose or volume, omission or modification of concomitant chemotherapy/immunotherapy, usage of induction chemotherapy and utilization of advanced molecular and imaging biomarkers and radiomics for selected subgroups of HPV⁺OPC patients. While promising data have been reported from various Phase II trials, evidence from Phase III de-escalation trials has failed to demonstrate improved outcomes. Therefore, further data and an improved risk stratification are required before de-escalated radiation treatments can be recommended outside of clinical trials.The review aims to outline current de-escalation strategies and future possibilities for enhancing patient outcomes in HPV⁺OPC.