Human Papillomavirus in Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

Simple Summary The causative role of human papillomavirus (HPV) in sinonasal squamous cell carcinoma (SNSCC) remains unclear and is hindered by small studies using variable HPV detection techniques. This meta-analysis aims to provide an updated overview of HPV prevalence in SNSCC stratified by detection method, anatomic subsite, and geographic region. From 60 eligible studies, an overall HPV prevalence was estimated at 26%. When stratified by detection method, HPV prevalence was lower when using multiple substrate testing compared to single substrate testing. Anatomic subsite HPV prevalence was higher in subsites with high exposure to secretion flow compared to low exposure subsites. HPV prevalence in SNSCC followed the global distribution of HPV+ oropharyngeal squamous cell carcinoma. Taken together, this meta-analysis further supports a role for HPV in a subset of SNSCCs. Human papillomavirus (HPV) drives tumorigenesis in a subset of oropharyngeal squamous cell carcinomas (OPSCC) and is increasing in prevalence across the world. Mounting evidence suggests HPV is also involved in a subset of sinonasal squamous cell carcinomas (SNSCC), yet small sample sizes and variability of HPV detection techniques in existing literature hinder definitive conclusions. A systematic review was performed by searching literature through March 29th 2020 using PubMed, Embase, and Web of Science Core Collection databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed by two authors independently. A meta-analysis was performed using the random-effects model. Sixty studies (n = 1449) were eligible for statistical analysis estimating an overall HPV prevalence of 25.5% (95% CI 20.7-31.0). When stratified by HPV detection method, prevalence with multiple substrate testing (20.5%, 95% CI 14.5-28.2) was lower than with single substrate testing (31.7%, 95% CI 23.6-41.1), highest in high-exposure anatomic subsites (nasal cavity and ethmoids) (37.6%, 95% CI 26.5-50.2) vs. low-exposure (15.1%, 95% CI 7.3-28.6) and highest in high HPV+ OPSCC prevalence geographic regions (North America) (30.9%, 95% CI 21.9-41.5) vs. low (Africa) (13.1, 95% CI 6.5-24.5)). While small sample sizes and variability in data cloud firm conclusions, here, we provide a new reference point prevalence for HPV in SNSCC along with orthogonal data supporting a causative role for virally driven tumorigenesis, including that HPV is more commonly found in sinonasal subsites with increased exposure to refluxed oropharyngeal secretions and in geographic regions where HPV+ OPSCC is more prevalent.