Treatment de-intensification and immunotherapy in human papillomavirus-related oropharyngeal squamous cell carcinoma – A review

Human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is increasingly prevalent among younger patients, necessitating treatment strategies that balance effective oncological outcomes with reduced treatment-related toxicities. Traditional concurrent chemoradiation has been linked to significant adverse effects, prompting research into de-escalation strategies aimed at minimizing treatment intensity without compromising survival rates. This paper reviews various de-escalation approaches under investigation, including reduced radiotherapy doses, alteration or omission of concomitant chemotherapy, and the use of induction chemotherapy for patient selection. Notable clinical trials such as MC1273, ECOG 3311, and ORATOR have shown promising results in maintaining oncological control while enhancing quality of life; however, definitive recommendations are limited due to the absence of positive Phase III evidence. In addition, immunotherapy, particularly checkpoint inhibitors, presents a potential avenue for replacing toxic chemotherapy due to the unique immunogenic profile of HPV+ tumors. Despite the encouraging findings from Phase I and II trials, the current clinical guidelines do not endorse de-escalated treatments outside clinical trials, emphasizing the need for ongoing research to establish validated, personalized treatment protocols that optimize outcomes for patients with HPV+ OPSCC.