BACKGROUND: Little information has been reported on regional and time trends of human papillomavirus (HPV) prevalence rates of oropharyngeal cancer (OPC) and non-OPC. METHODS: The study consisted of a systematic review and meta-analysis using random effects logistic regression models. RESULTS: Overall HPV prevalence in OPC (47.7%; 95% confidence interval [CI], 42.9-52.5%) increased significantly over time: from 40.5% (95% CI, 35.1-46.1) before 2000, to 64.3% (95% CI, 56.7-71.3) between 2000 and 2004, and 72.2% (95% CI, 52.9-85.7) between 2005 and 2009 (p <.001). Prevalence increased significantly in North America and Europe, and the significant gap between them that existed before 2000 (50.7% vs 35.3%, respectively, p = .008) has now disappeared (69.7% vs 73.1%, respectively, p = .8). Prevalence in non-OPC (21.8%; 95% CI, 18.9-25.1%) has not increased over time (p = .97) CONCLUSIONS: The sharp increase in the proportion of HPV-positive OPC over the last decade has occurred at a faster rate in Europe compared with that in North America. In contrast, the relatively low prevalence of HPV in non-OPC remains unchanged. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.