Personalised treatment in hpv-positive oropharyngeal squamous cell cancer: Insights from molecular biology to clinical trials

ObjectiveTo review current evidence on the epidemiology, molecular biology, and evolving treatment strategies of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), with particular emphasis on treatment de-escalation and personalized therapeutic approaches.Data SourcesA systematic literature search was performed using PubMed/MEDLINE, Scopus, Web of Science, Embase, and ClinicalTrials.gov. Studies published between January 2000 and March 2026 were identified using keywords related to HPV-positive OPSCC, tumor biology, treatment de-escalation, immunotherapy, and circulating tumor HPV DNA. Of 145 records retrieved, 25 duplicates were removed and 120 studies were screened. Following full-text assessment, 67 HPV-positive OPSCC-related studies were included in the final qualitative synthesis.Data SummaryHPV-positive OPSCC has emerged as a distinct clinical and biological entity with rapidly increasing incidence, particularly in high-income regions. Compared with tobacco-associated head and neck cancers, HPV-positive disease affects younger individuals and demonstrates improved treatment responsiveness and survival outcomes. Viral oncoproteins disrupt cell-cycle regulation, immune surveillance, and genomic stability, driving tumor development. Despite favorable survival, long-term treatment-related morbidity remains significant. Consequently, numerous clinical trials are evaluating treatment de-escalation strategies, including reduced-dose radiotherapy, modified systemic therapy, and surgery-based approaches in selected patients.ConclusionsAdvances in molecular understanding and biomarker-driven approaches are shaping personalized management strategies for HPV-positive OPSCC. Carefully designed clinical trials and improved patient selection are essential to optimize oncologic outcomes while minimizing treatment-related toxicity.