Beyond stage and HPV status: the evolving landscape and future of multidisciplinary deintensification in human papillomavirus-related oropharyngeal cancer

The rising incidence of oropharyngeal cancer (OPC), primarily driven by human papillomavirus (HPV), presents a significant public health challenge. Given the markedly better prognosis associated with HPV-positive OPC, there is a compelling need to balance oncologic efficacy and reduce treatment morbidity. Although early de-escalation trials did not change standards, selective, biomarker-informed strategies show promise. This review synthesises evidence across transoral robotic surgery (TORS), reductions in RT dose and elective volumes, systemic therapy modification and the integration of circulating HPV DNA, immune profiling and functional imaging to guide truly personalised de-escalation. Ultimately, successful deintensification will require integration of biomarkers, multidisciplinary collaboration and patient-centred decision-making, moving beyond stage and HPV status alone.