HPV-Positive Oropharyngeal Cancer: An Umbrella Review of Global Prevalence and Survival Outcomes

Human papillomavirus (HPV) has transformed oropharyngeal cancer (OPC) epidemiology, creating distinct disease entities. This umbrella reviews synthesized evidence on HPV-positive OPC prevalence and survival. Four databases were searched for systematic reviews (SRs) examining HPV prevalence and survival in OPC. Meta-analysis was performed using random effects methodology. Quality was assessed using A Measurement Tool to Assess systematic Reviews 2 (AMSTAR 2) and evidence certainty was rated by utilizing Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. A Corrected Covered Area (CCA) analysis was conducted to measure the degree of overlapping literature among the included SRs. Twenty-four SRs encompassing 783 primary studies and 146,218 OPC patients were included. Overall HPV prevalence was 43% (95% CI: 41-46%). HPV-16 predominated (79%), with highest prevalence in tonsils (60%), followed by base of tongue (43%). The pooled prevalence of HPV in soft palate was 8%. Males showed higher prevalence than females (47% vs. 35%). North America had the highest regional prevalence (59%), followed by Oceanica (49%), Europe (44%), and Asia (37%). The comparison of the meta-analyses (MAs) before and after 2020 showed a reduction in prevalence from 48% to 41%, although the difference was not statistically significant. For the virus detection method, p16 and in situ hybridization positivity resulted in higher prevalences compared to Polymerase Chain Reaction (PCR) alone. Significant presence of heterogeneity and publication bias, large CIs and the observational nature of the included study designs led to "low" evaluation of all the pooled analyses assessed by GRADE. HPV-positive patients demonstrated superior survival outcomes, though HPV-non16 subtypes showed poorer prognosis. In conclusion, HPV affects nearly half of OPC cases globally, with significant anatomical, demographic, and geographic variations. These findings support individualized treatment approaches beyond binary HPV status classification.