Immunohistochemical Study of the Role of Human Papillomavirus, Epstein–Barr Virus, and P16INK4a Expression in Head‑and‑Neck Squamous Cell Carcinomas

Abstract

Background: Studies over the years have established that human papillomavirus (HPV) and Epstein–Barr virus (EBV) are major etiological agents in subsets of head‑and‑neck squamous cell carcinomas (HNSCCs). This study further explores the concurrence of HPV and EBV together with P16^INK4a expression in HNSCCs, providing additional insights into their unique role in establishing a virus‑induced carcinogenesis. Materials and Methods: A retrospective cross‑sectional study utilizing immunohistochemistry was employed to establish the presence of HPV, EBV, and P16^INK4a expression in HNSCC archived tissue samples. Results: A total of 121 selected HNSCC cases were included in the study, with male preponderance (n = 86) and majority of the cases occurring in patients ≤54 (n = 62). The most common site of occurrence was the oral cavity (n = 29), followed by larynx (n = 27) and nasal cavity and paranasal sinuses (n = 24), respectively. The study recorded 18 (14.9%) HPV‑positive tumors, 7 (5.8%) EBV‑positive tumors, and 2 (1.7%) tumors coinfected with HPV and EBV. P16^INK4a expression was recorded in 42.1% (n = 51) of the tumors. Although P16^INK4a expression correlated weakly with both HPV (r = 0.116) and EBV (r = 0.205) positivity, it showed a statistically significant expression with EBV positivity (p = 0.024). Conclusion: The observed pattern of HPV association with P16^INK4a overexpression was consistent with earlier reported studies, and as such, the study reinforces the assertion that P16^INK4a can be used as a surrogate marker for HPV‑positive tumors. However, additional studies are required to validate its suitability in tumor sites other than oropharyngeal squamous cell carcinoma.