Redefining oropharyngeal cancer in the HPV era: integrating precision medicine and immunotherapeutic frontiers

Oropharyngeal cancer (OPC) is increasingly driven by human papillomavirus (HPV), particularly HPV16, marking a shift in its epidemiology, prognosis, and treatment approach. This review explores the distinct molecular biology of HPV-positive OPC, highlighting how it differs from tobacco-related cases in terms of tumor behavior, immune environment, and therapeutic response. Advances in immunotherapy and biomarker-guided strategies have improved outcomes for some patients, though challenges such as resistance, variable biomarker accuracy, and limited vaccine uptake remain significant. Emerging technologies such as artificial intelligence, liquid biopsies, and nanotechnology demonstrate encouraging diagnostic and prognostic potential; however, most current data derive from early-phase or retrospective studies with limited external validation. Their translation into routine clinical practice will require prospective, multi-institutional validation to ensure reproducibility and clinical utility. Gaps in HPV vaccination coverage and access to novel therapies, especially in low-resource settings, further complicate global disease control. By outlining both current practices and future directions, this review emphasizes the need for evidence-based, equitable approaches to improving outcomes for patients with HPV-associated OPC.