Purpose/Objective(s): Outcomes following recurrence or metastasis of Human Papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) have not been studied extensively. Herein, we report patterns of failure and the natural history following recurrence in a large cohort of locally advanced OPC patients treated with definitive loco-regional treatment using modern radiation techniques (IMRT). Materials/Methods: We reviewed outcomes from 734 consecutive locally advanced OPC patients treated with definitive chemoradiation using IMRT between July 2001 and December 2013 at a large cancer center. HPV/p16 status was available for 417 OPC patients (56.8%) with 302 HPV+ patients (72.4%) and 115 HPV-patients (27.6%). We compared patterns of failure between HPV+ and HPV-OPC cases as well as survival following locoregional recurrence (LRR) recurrence or distant metastasis (DM). Median follow-up was 63.8 months in surviving patients. Survival rates were estimated using the Kaplan-Meier method and compared with log-rank testing. Results: Five year rates of local control, regional control, distant control and overall survival in HPV+ vs HPV-OPC were 94.6% vs. 84.2% (P Z 0.001), 93.2% vs 85.9% (P Z 0.011), 92.2% vs 79.1% (P < 0.001) and 86% vs 69.2% (P < 0.001). Time to progression was not significantly different between HPV+ and HPV-OPC (10.3 vs 10.6 months, respectively). The proportion of patients with isolated LRR did not differ between the two groups: 78% of LRRs were isolated in HPV+ OPC vs. 77% in HPV-OPC. Time from DM to death was not significantly different between HPV+ and HPV-OPC (16.1 vs. 20.2 months, P Z NS) but time from isolated LRF to death was significantly longer in HPV+ OPC compared to HPV-(median 36.5 vs 18.8 months, P Z 0.04). Conclusion: HPV+ and HPV-OPC display similar proportions of local, regional and distant failures. Survival following DM is independent of HPV/p16 status but survival following LRR in HPV+ OPC is favorable compared to HPV-disease. HPV status is an important factor to consider in the design of clinical trials for recurrent OPC, particularly in the setting of isolated locoregional recurrence.
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