Prevalence of Human Papillomavirus and Co-Infection with Epstein-Barr Virus in Oral and Oropharyngeal Squamous Cell Carcinomas

BACKGROUND: Head and neck squamous cell carcinoma is one of the most important malignancies, worldwide. Oncogenic viruses, such as human papilloma virus (HPV) and Epstein-Barr virus (EBV), are linked to these cancers and studies suggest a possible interaction between HPV and EBV during co-infections to promote oncogenesis. Nonetheless, these reports are controversial and demand more investigations in this regard. The present work to assessed the prevalence of HPV and co-infection with EBV in oral and oropharyngeal squamous cell carcinomas. METHODS: Formalin-fixed paraffin-embedded tissues were collected from 166 archived oral and oropharyngeal squamous cell carcinoma samples from Ahvaz Imam Khomeini hospital, Ahvaz, Iran, from March 2013 and December 2019. Nested-PCR was used to detect the viruses and type-specific PCR/nested-PCR and sequencing were performed for virus genotyping. Results: Out of the 166 specimens, 84.33% and 16.42% were from oral cavity and oropharynx, respectively; of which, 32 cases (19.3%) were HPV-positive (16.42% of oral cavity and 34.6% of oropharynx). HPV was detected in 36.36%, 25%, and 16.42% of base of tongue, tonsil, and oral tongue tumors, respectively. HPV was more associated with well differentiated tumors (24;18.04%) in compared to moderately and poorly differentiated ones. Regarding HPV-16 genotyping, 7 (21.8%) out of the 32 samples were found to be HPV-16 (4/26 (15.38%) for oropharynx and 3/140 (2.14%) for oral cavity). Moreover, 90 samples were evaluated for EBV infection and co-infection; of which, 4 (4.4%) subjects tested positive for EBV, including two cases with HPV co-infection. All the positive cases were EBV type B, from oral cavity, and histologically well differentiated. CONCLUSIONS: HPV was more associated with oropharyngeal cancer. This association has been linked to various factors such as repeated oral and oropharyngeal exposure to HPV due to change in patterns of sexual behaviors; a phenomenon that may demand routine HPV vaccination.