Human Papillomavirus Infection as a Risk Factor for Oral Leukoplakia: A Systematic Review and Meta-Analysis

The correlation between human papillomavirus (HPV) infection and cervical neoplasia has been well documented. Nonetheless, its correlation with the progression of oral cancer and oral leukoplakia (OL) remains contentious. We aimed to conduct a comprehensive meta-analysis to examine the most recent evidence on the association between HPV infection and OL.

The protocol was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocol, INPLASY (INPLASY202540033) and complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PRISMA 2020 requirements. A systematic literature review was performed using the electronic databases PubMed, Scopus and Wiley Library without any date or time restrictions to identify observational studies that documented any association between HPV and OL. A pooled odds ratio (OR) estimate and its associated 95% confidence interval (CI) were calculated utilising the random effects model. The I² statistic and Cochran's Q test were used to evaluate heterogeneity among studies. Sensitivity analysis and credibility ceiling tests were conducted to assess the robustness of the findings.

The database search retrieved 1716 articles, out of which 32 articles were selected for final analysis, meeting the inclusion criteria. The overall pooled OR and the corresponding 95% CI, estimated from a total of 1236 cases and 2916 controls in a random-effects model, demonstrated a positive association between HPV detection in OL (OR = 3.16; 95% CI, 2.06-4.95). OL was more strongly associated with high-risk HPV than low-risk HPV (OR = 5.42; 95% CI, 2.52-11.69 and OR = 1.90; 95% CI, 1.10-3.29, respectively). The sensitivity analysis and credibility ceiling test validated the robustness of the finding.

Oral HPV infection, especially with high-risk HPV, is significantly associated with OL. Further prospective trials are encouraged to validate these results and elucidate the exact role of HPV in OL.