Human papillomavirus (HPV) and Epstein-Barr virus (EBV) in keratinizing versus non- keratinizing squamous cell carcinoma of the oropharynx

Background: Oral and oropharyngeal squamous cell carcinomas (OSCC and OPSCC) represent the majority of head and neck squamous cell carcinomas (HNSCC). Human papillomavirus (HPV) is an important etiologic factor together with Epstein-Barr virus (EBV). Little is known on the prevalence of major herpesviruses [EBV, cytomegalovirus (CMV) and HHV-6, - 7 and - 8] in HNSCCs. Methods: Fifty-one formalin-fixed paraffin-embedded (FFPE) tissue samples taken at surgery (40 oropharyngeal, 11 oral) were analyzed for 40 HPV genotypes (20 high-risk types), EBV, CMV, HHV-6, - 7 and - 8 by quantitative PCR. Expression of the HPV-induced p16INK4A protein was also investigated by immunohistochemistry (IHC). Results: In SCC, the prevalence of EBV was significantly higher compared to that of HPV (EBV 51% vs. HPV 19.5%; P = 0.005). HPV infection was found in 25% of OPSCC and in none of the OSCC; conversely, higher prevalence of EBV was found in OSCC (72.7%). HPV and EBV co-infection was detected only in 4 (10%) OPSCC. CMV was detected in only two cases, whereas HHV-6, - 7 and - 8 resulted negative. The prevalence of HPV but no EBV was associated with the non-keratinizing SCC type (NKSCC) compared to the keratinizing SCC type (KSCC)(HPV-DNA P < 0.005; EBV = 0.054). Conclusions: Single HPV or EBV positivity was higher in OSCC than in OPSCC. Other potentially oncogenic herpesvirus types were minimally or not represented.