Objectives: We aimed to provide pooled estimates of human papillomavirus (HPV) prevalence in oral potentially malignant disorders (OPMD) and evaluate the impact of presence of epithelial dysplasia. Methods: We searched PubMed, Embase, and Cochrane Library databases for studies that examined the prevalence of HPV DNA in OPMD tested by polymerase chain reaction (PCR). Results: Across 52 eligible studies (2,677 cases), we found an overall pooled HPV prevalence of 22.5% (95% confidence interval [CI] 16.6–29.0). Between-study heterogeneity was 93%. When stratified by subgroup, the pooled HPV prevalence in leukoplakia (1,232 cases) was 20.2% (95% CI 11.2–31.1), lichen planus (767 cases) 23.0% (95% CI 15.0–32.2), oral submucous fibrosis (238 cases) 28.6% (95% CI 23.0–34.5), proliferative verrucous leukoplakia (60 cases) 24.7% (95% CI 1.8–62.0), and OPMD unspecified (377 cases) 25.4% (95% CI 16.2–35.8). Information on presence of epithelial dysplasia was available in 19 studies, and the results did not vary substantially between non-dysplastic and dysplastic samples. HPV16 was the predominant genotype among HPV-positive OPMD cases (48.2%, 95% CI 31.4–65.2). Conclusion: We found a pooled HPV DNA prevalence of 22.5% in OPMD cases with great between-study heterogeneity. The HPV prevalence appeared to be comparable across subgroups and independent of epithelial dysplasia.