Human papillomavirus and WHO type I nasopharyngeal carcinoma

Abstract

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; 5 of 6 were HPV-16-positive by PCR and 4 of 8 were HPV-positive by ISH; only 2 of 8 (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, though larger studies are needed to verify these findings.

Human papilloma virus detection in neoplastic and non-neoplastic nasopharyngeal tissues in Taiwan

“…Also, of the latter four studies18 23–25 from areas non-endemic for NPC and including HPV-positive WHO-I NPCs, only one18 found co-infection of EBV in HPV-positive WHO-I NPCs. In contrast, of the six studies13 18 19 22 24 25 from non-endemic areas including HPV-positive WHO-II/III NPCs, four13 18 22 24 showed co-existence of EBV in HPV-positive WHO-II/III NPC cases. Thus, in both endemic and non-endemic areas, HPV infection occurs more commonly in WHO-I NPCs than in WHO-II/III NPCs.…”

“…Also, compared with HPV-positive WHO-II/III NPCs, HPV-positive WHO-I NPCs are less likely to be EBV-positive. These observations raise the possibility that HPV infection may be important in the pathogenesis of some EBV-negative WHO-I NPCs 19 25. Further investigations are required to clarify this issue.…”

Oncogenic human papillomavirus-associated nasopharyngeal carcinoma: an observational study of correlation with ethnicity, histological subtype and outcome in a UK population

“…The reported incidence of HPV in NPC ranges from 9–52.9% [8-10,12-14]. Although this wide range may be attributed to differences in geographic variation with regard to aetiology and prevalence of NPC, it is more likely a result of non-standardised viral detection methods.…”

The interaction between human papillomavirus and other viruses

“…Although both low-risk and high-risk HPVs (6, 11, 16, and 18) were detected, HPV16 and 18 were more prevalent, accounting for 66.7% of HPV-positive NPC tumors in a Chinese cohort (Tung et al, 1999). In contrast, co-infections were rarely detected in NPC from non-endemic areas (Stenmark et al, 2014), and several studies have suggested that HPV and EBV appear to be mutually exclusive in NPC with oncogenic HPV types 16, 18, 39, 45, and 59 only detected in EBV-negative NPC (Dogan et al, 2014; Lin et al, 2014; Lo et al, 2010; Maxwell et al, 2010; Robinson et al, 2013). The presence of EBV or HPV in NPC correlated with an overall improved survival compared to virally-negative NPC, a similarity noted for HPV-positive OSCC (Dogan et al, 2014; Stenmark et al, 2014).…”