Different Pattern of Treatment Failure After Chemoradiation Between p16+ and p16- Patients Affected by Oropharyngeal Carcinoma.

Gili, Riccardo; Bossi, Paolo; Lalli, Luca; Licitra, Lisa Francesca Linda; Maddalo, Marta; Bacigalupo, Almalina; Belgioia, Liliana; Cacicedo, Jon et al. · Head Neck · 2026

retrospective_cohort · Level III

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Abstract

Oropharyngeal cancer (OPC) exhibits distinct clinical behaviors according to HPV/p16 status and smoking exposure. While HPV-positive OPC generally shows superior survival, differences in recurrence patterns remain unclear. A retrospective multicenter analysis of 674 AJCC VII edition Stage III-IVa/b OPC patients treated with definitive IMRT ± systemic therapy was conducted across 14 Southern European centers. Recurrence patterns, disease-free survival (DFS), overall survival (OS), and survival after recurrence (rOS) were compared between p16 groups and across smoking categories. HPV-positive tumors showed a higher incidence of distant recurrence, particularly among heavy smokers, while p16-negative OPC displayed predominantly locoregional failure. p16-positive patients had significantly better DFS, OS, and rOS. Recurrence patterns in OPC differ by HPV status and smoking history. HPV-positive heavy smokers represent a distinct high-risk subgroup characterized by increased distant metastasis and inferior survival, warranting refined stratification beyond p16 status alone.

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