The role of human papillomavirus in oral squamous cell and verrucous carcinomas: a systematic review with case series

Introduction: Oral cancer (OC), particularly squamous cell carcinoma and its variants such as verrucous carcinoma, represents a growing public health concern due to increasing global incidence. While tobacco and alcohol remain the main risk factors, attention has turned to the potential role of human papillomavirus (HPV), particularly with particular consideration on high-risk genotypes. Objective: This systematic review evaluates current evidence on the association between HPV and OC. Methods: A structured search was conducted in PubMed, Scopus, and Web of Science using keywords including “oral carcinoma,” “oral squamous cell carcinoma,” “oral verrucous carcinoma,” and “HPV.” Screening followed PRISMA guidelines, and 15 articles were selected. Additionally, a case series of patients treated at the Department of Interdisciplinary Medicine, University of Bari “Aldo Moro,” are presented to provide clinical context. Results. The evidence suggests a possible association between HPV infection, especially genotype 16, and a subset of oral squamous cell carcinomas. However, differences in detection techniques and study design contribute to variability in findings. Conclusion: While HPV may play a role in oral carcinogenesis, further high-quality studies are required to clarify its impact. These findings may have implications for screening, prognosis, and prevention strategies, including HPV vaccination.