Co-Incidence of Human Papillomaviruses and Epstein-Barr Virus is Associated with Advanced Tumor Stage: A Tissue Microarray Study of Head and Neck Cancers

Abstract

Background: Human papillomaviruses (HPVs) and Epstein-Barr virus (EBV), are known oncoviruses and can be co-present and hence cooperate in the development of human carcinomas, including head and neck. Methods: We herein explore for the first time the co-prevalence of high-risk HPVs and EBV in 98 head and neck (HN) squamous cell carcinoma (SCC) tissues from Bosnian patients using polymerase chain reaction (PCR) and immunohistochemistry (IHC) analysis, as well as tissue microarray methodology. Results: The majority of these cancer tissue cases were from the oral cavity (68%). We found that high-risk HPVs and EBV are co-present in 34.7% of SCC samples; with a significant correlation between various high-risk HPV types and EBV co-incidence (p=0.03). Our data showed that 30.8% of oral SCCs are positive for E6 oncoproteins of high-risk HPVs and 44.6% are positive for LMP1 of EBV. The most commonly expressed HPVs in our HNSCC samples include HPV types 16, 18, 45 and 58. More importantly, 37.5% of oral SCCs are positive for both HPVs and EBV, with statistically significant association between high-risk HPV types and EBV (p<0.05). More significantly, we report that the co-presence of HPV and EBV is highly correlated with advanced tumor stage (p=0.035). Conclusion: In conclusion, HPV and EBV oncoviruses are co-present in HNSCC, particularly in oral cancer, where they can cooperate in the initiation and/or progression of this cancer. Thus, further studies are necessary to elucidate the mechanism of high-risk HPVs and EBV cooperation in human carcinomas