Human Papillomavirus–Attributable Head and Neck Cancers in India—A Systematic Review and Meta-Analysis

Abstract

PURPOSE Head and neck cancer accounts for about one third of the global burden in India. Mucosal high-risk human papillomavirus (HPV) has been hypothesized as a contributory risk factor for head and neck cancer (HNC) but its prevalence in Indian patients is not well established. Therefore, this systematic review and meta-analysis aimed to estimate the prevalence of HPV in HNC in India and their attributable fraction by considering the biomarkers of carcinogenesis, p16, and HPV E6/E7 mRNA. METHODS A systematic literature search was done in Medline via PubMed, Embase, Scopus, ScienceDirect, ProQuest, and Cochrane to identify studies on HPV and HNC in the Indian population, published between January 1990 and October 2022. Fifty-four eligible studies were identified and relevant clinical information was collected. Meta-analysis was conducted to estimate the pooled prevalence of HPV DNA, p16INK4a, and E6/E7 mRNA percent positivity by random-effect logistic regression model using Metapreg, STATA 18. RESULTS Thirty-four high-quality studies were taken for meta-analysis. The pooled prevalence of HPV in HNC was 20% (95% CI, 12 to 32) with a high level of heterogeneity ( I2 = 90.79%). The proportion of HPV in oropharyngeal cancer (OPC; 22% [95% CI, 13 to 34]) and laryngeal cancer (LC; 29% [95% CI, 17 to 46]) was higher than in oral cancer (OC; 16% [95% CI, 8 to 30]). The HPV-attributable fraction of OPC, considering the E6/E7 mRNA and p16 positivity, was 12.54% and 9.68%, respectively, almost similar to LC (11.6% and 9.57%), while it was much lower in OC (3.36% and 4%). CONCLUSION The HPV-attributable fraction is considerably lower for OC, suggesting a negligible causative role of HPV in OC. A significant proportion of OPC and LC are attributed to HPV; however, their exact causative role is unclear because of the presence of other known risk factors.