Human Papillomavirus and WHO Type I Nasopharyngeal Carcinoma

Objectives: Nasopharyngeal carcinoma (NPC) is a rare cancer in the United States. An association between NPC and Epstein-Barr virus (EBV) is well-established for World Health Organization (WHO) types II and III (WHO-II/III) NPC but less well-established for WHO type I (WHO-I) NPC. Given the rise in oropharyngeal tumors positive for high-risk human papillomavirus (HPV) and the unique biology of WHO-I NPC, we examined the relationship between HPV and WHO-I NPC. Study Design: Retrospective case-comparison study. Methods: A search of a large multidisciplinary cancer center tumor registry identified 183 patients seen from January 1999 to December 2008 with incident NPC and no prior cancer. Available paraffin-embedded tumor specimens (N = 30) were analyzed for oncogenic HPV status by in situ hybridization (ISH) and polymerase chain reaction (PCR) for HPV-16 and HPV-18; EBV status by ISH; and p16 expression by immunohistochemistry. Demographic parameters, including race and smoking, were obtained from the medical records. Results: Among the 18 WHO-I NPC patients, 66% (N = 12) were smokers and 17% (N = 3) Asian; among the 165 WHO-II/III NPC patients, 44% (N 73) were smokers and 24% (N = 39) Asian. Eight WHO-I NPC patients had available paraffin blocks; five of six were HPV-16-positive by PCR and four of eight were HPV-positive by ISH; only two of eight (25%) were EBV-positive. Twenty-two WHO-II/III NPC patients had available paraffin blocks; only 1 was HPV-positive by ISH, and 13 of 22 (60%) were EBV-positive. Conclusions: These results suggest that WHO-I NPC is associated with oncogenic HPV, although larger studies are needed to verify these findings.