Global HPV genotype distribution and coinfections in oropharyngeal squamous cell carcinoma: systematic review and meta-analysis

PURPOSE: This study systematically reviewed and meta-analyzed the global prevalence and genotype distribution of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: Six databases and gray literature were searched and identified studies of biopsy-confirmed OPSCC with HPV detected by molecular methods. A meta-analysis was performed using random-effects generalized linear mixed models to calculate pooled prevalence estimates with 95% confidence intervals. Temporal trends were explored by meta-regression, and risk of bias was assessed using Joanna Briggs Institute tools. RESULTS: A total of 183 studies with 34,627 OPSCC patients from 35 countries were included; of these, 17,443 were HPV-positive with available genotyping data. The meta-analysis showed that HPV16 was the predominant genotype (92.5% of single infections), followed by HPV33 (3.3%), HPV18 (2.8%), and HPV35 (2.8%). Coinfections were rare (1.3%), most frequently involving HPV16 with other high-risk genotypes such as HPV18, 33, and 31. Meta-regression revealed a temporal decline in HPV16 concurrent with a rise in non-HPV16 genotypes. CONCLUSION: HPV16 remains the predominant genotype in OPSCC worldwide, the contribution of other oncogenic types is increasing. These findings reinforce the importance of HPV genotyping to support surveillance and vaccination strategies and to improve understanding of HPV-driven OPSCC tumor biology.