Outcomes of p16-Positive EBV-Negative Nasopharyngeal Carcinoma Treated with Definitive Chemoradiation at a Large North American Cancer Center

Abstract

There is a subtype of nasopharyngeal carcinoma (NPC) that is not associated with the Epstein Barr virus (EBV), but instead appears to be human papilloma virus (HPV)-related. Existing single-institution series are conflicting on the prognosis of this group. It remains unclear whether the outcomes are significantly different than EBV-driven NPC, and if this population carries a favorable prognosis as it does in HPV-related oropharyngeal carcinoma (OPC). Here, we compared the outcomes and assessed the prognostic implications between HPV-related and EBV-driven NPC patients. We retrospectively identified 58 consecutive patients with newly diagnosed, non-metastatic nasopharyngeal cancer treated with definitive radiation therapy (RT) between 2005 and 2016 at our institution for whom EBV and p16 status was available, which was used as a surrogate marker for high-risk HPV. Endpoints included local, regional, and distant control, and overall survival. Survival was estimated using the Kaplan-Meier method and cox proportional hazard models were utilized. We identified 17 patients with p16+ EBV- NPC, of which 13 were also confirmed to be HPV+ by immunohistochemistry, 2 were HPV-, and 2 had no HPV testing available. An additional 35 patients were EBV+ p16-, of which the 12 for whom HPV testing was available showed no HPV positivity. We found no cases that were both EBV+ and p16+. All patients were treated with definitive chemoradiation to 70 Gy with IMRT except three with T1 N0 disease that received radiation alone. In the p16+ group, 35% (6) received concurrent and adjuvant chemotherapy, 53% (9) received concurrent only, and 5.9% (1) underwent induction and concurrent treatment; in the EBV+ group, the respective proportions were 51% (18), 34% (12) and 8.5% (3) and not significantly different from the p16+ cohort (p=0.628). p16+ EBV- patients were significantly older (mean age 59.8 years vs. 49.6, p=0.013) and had more advanced T stage (53% T4 vs. 23%, p=0.026) than p16- EBV+ patients. With a median follow-up of 14.3 months, 7 locoregional failures (LRF), 7 distant failures (DF), and 4 deaths, we found no significant difference in overall survival (OS; p16+ EBV- vs. p16- EBV+, HR 2.49, p=0.401), locoregional control (HR 2.40, p=0.407), progression free survival (PFS; HR 1.39, p=0.589), or distant metastasis (HR 0.78, p=0.763) between the two groups. Controlling for the advanced T stage and age of p16+ patients, we did not find p16 status to predict for LRF, DF, or OS on multivariate analysis. HPV-related NPC apparently does not portend a significantly different outcome than EBV-related NPC in our data, despite presenting with older age and more advanced T-stage. Given our results and the rare incidence of HPV-related NPC, further multi-institutional studies will be necessary to validate these findings.