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

Abstract

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.

Keywords: anatomic subsite; detection method; human papillomavirus; prevalence; sinonasal squamous cell carcinoma.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart depicting the study selection process.

Figure 2

HPV prevalence distribution by sinonasal anatomic subsite. (A). Sagittal section of the nasal cavity with arrows displaying the entry and distribution of HPV prevalence estimates by anatomic subsite using the random-effects model. (B). HPV prevalence estimates stratified by high- and low-exposure anatomic subsites. * With multiple subgroups in one study, Comprehensive Meta-Analysis (CMA) program will see each subgroup as a separate study. Hence, a total of 71 studies here. ^ Only calculated using the fixed-effects model.

Figure 3

HPV prevalence in sinonasal squamous cell carcinoma (SNSCC) stratified by geographic region for oropharyngeal squamous cell carcinoma (OPSCC) and SNSCC demonstrating paired prevalence rates using the random-effects model. Studies from India and Japan were removed from the Asian SNSCC data as they were felt to introduce bias as these counties were not represented in the OPSCC data. * Source: Jalouli et al., (2010) [84] and Jalouli et al., (2012) [85]. ^ Source: Ndiaye et al., (2014) [86].

Figure 4

HPV prevalence by subgroup. (A). Bar chart depicting an overview of HPV prevalence per subgroup. (B). HPV prevalence per subgroup using only data from North America. (C). North American data stratified by testing method.