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

Background 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.Methods 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.Results 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.Conclusion 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.