A Metagenomic Analysis of the Virome of Inverted Papilloma and Squamous Cell Carcinoma.

Abstract

Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The role of HPV in its pathogenesis has been controversial. The purpose of this study was to determine theviromeassociated with IP, with progression to carcinoma-in-situ, and invasive carcinoma. To determine the HPV-specific types, a metagenomics assay that contains 62,886 probes targeting viral genomes in a microarray format was used. The platform screens DNA and RNA from fixed tissues from 8 control tissue, 16 IP without dysplasia, 5 IP with carcinoma-in-situ, and 13 IP-associated squamous cell carcinoma (IPSCC). Paired with next-generation sequencing, 48 types of HPV with 857 region-specific probes were interrogated against the tumors. The prevalence of HPV16 was 14%, 42%, 70% and 73% in control tissue, IP without dysplasia, IP with CIS, and IPSCC, respectively. The prevalence of HPV18 had a similar progressive increase in prevalence, with 14%, 27%, 67%, and 74%. The assay allowed region-specific analysis which identified the only oncogenic HPV type 18 E6 to be statistically significant when comparing to control tissue. The prevalence of HPV18-E6 was 0% in control tissue, 25% in IP without dysplasia, 60% in IP with CIS, and 77% in IPSCC. There are over 200 HPV types that infect human epithelial cells, of which only a few are known to be high-risk. Our study demonstrated a trend of increasing prevalence of HPV18-E6 that correlated with histologic severity, which is novel and supports a potential role for HPV in the pathogenesis of IP. This article is protected by copyright. All rights reserved.