BACKGROUND: The significance of human papillomavirus (HPV) in nasopharyngeal carcinomas (NPCs) in a low-incidence population remains unknown. METHODS: Samples from 90 patients with NPC (years, 1957-2012) were analyzed for Epstein-Barr virus (EBV). Clinical data, EBV, HPV, and p16 status were correlated with overall survival (OS; 63 cases; years, 1981-2012). RESULTS: Of 9 HPV-positive cases, 3 extended from extra-nasopharyngeal sites. Nasopharyngeal origin was confirmed in 6 cases. HPV-positive NPC had OS similar to EBV-positive NPC (85 vs 141 months; p > .05). The OS of patients with EBV/HPV-negative NPC was worse (34 months; p = .004). Nonkeratinizing histology was associated with better outcome than keratinizing (115 vs 25 months; p = .001). Over the last several decades, the proportion of keratinizing NPC decreased from 34.5% to 14.3% (p = .026). CONCLUSION: The etiologic role of HPV in NPC is confirmed. The favorable prognostic significance of HPV positivity is similar to that of EBV positivity. © 2013 Wiley Periodicals, Inc. Head Neck, 2013.