
Human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is rising, surpassing cervical cancer as the predominant HPV-induced cancer in developed regions. While standard treatments yield positive outcomes for HPV+ OPSCC patients, the focus is shifting toward reducing treatment intensity. However, recent multi-centre trials failed to establish the non-inferiority of de-escalation strategies at a population level, emphasizing the need for precision medicine. This review explores the heterogeneity within HPV+ OPSCC, seeking biomarkers for patient stratification and personalized treatment. It delves into clinical, morphological, and molecular perspectives, examining the challenges and potential future directions, including addressing racial and ethnic differences.
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