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.

The contemporary management of cancers of the sinonasal tract in adults

“…Tumors are often slow‐growing, and local symptoms are most common 289 . Delayed diagnosis is common and is made on average 6 months after the onset of symptoms 15,290 . Cervical adenopathy because of nodal metastasis may be a presenting symptom in 9%–22% of patients with a new ONB diagnosis 291 …”

Sinonasal Squamous Cell Carcinoma, a Narrative Reappraisal of the Current Evidence

“…Similar to some HNSCCs, transcriptionally active human papillomavirus (HPV) has been found in some SNSCCs, though the causative role of viral infection and its prognostic implications are still a matter of debate [ 9 ]. However, recent publications converge in stating that HPV probably has a role in determining SNSCC and implies a better prognosis compared to HPV-negative tumors [ 10 , 11 , 12 ]. In a similar fashion, Epstein–Barr virus (EBV) has been detected in a relevant proportion of SNSCCs [ 13 , 14 ].…”

Mismatch Repair Deficiency and Somatic Mutations in Human Sinonasal Tumors

“…HPV-positive tumors made up only a small proportion and correlated significantly with the histological phenotype of tumors with squamous cell differentiation ( p < 0.001) in our tumor population, which may be underrepresented, as not all cases could be tested for HPV. In the literature, up to 31.5% of SNSCC are HPV positive [ 53 ], and HPV is more commonly found in sinonasal subsites with increased exposure to refluxed oropharyngeal secretions and in geographic regions where HPV+ oropharyngeal squamous cell carcinoma (OPSCC) is more prevalent [ 54 ]. In our cohort, the frequency of HPV high-risk infection was 5.25% in all tested cases (3/57), and only one exophytic sinonasal papilloma (ESP) (16.7%,1/6), one ISP-associated carcinoma (10%, 1/10) and one SNSCC non-keratinizing (7.7%, 1/13) were affected.…”