학술논문
Phylogenomic Analysis of Human Papillomavirus Type 31 and Cervical Carcinogenesis: A Study of 2093 Viral Genomes
Document Type
article
Author
Maisa Pinheiro; Ariana Harari; Mark Schiffman; Gary M. Clifford; Zigui Chen; Meredith Yeager; Michael Cullen; Joseph F. Boland; Tina Raine-Bennett; Mia Steinberg; Sara Bass; Yanzi Xiao; Vanessa Tenet; Kai Yu; Bin Zhu; Laurie Burdett; Sevilay Turan; Thomas Lorey; Philip E. Castle; Nicolas Wentzensen; Robert D. Burk; Lisa Mirabello
Source
Viruses, Vol 13, Iss 10, p 1948 (2021)
Subject
Language
English
ISSN
1999-4915
Abstract
Human papillomavirus (HPV) type 31 (HPV31) is closely related to the most carcinogenic type, HPV16, but only accounts for 4% of cervical cancer cases worldwide. Viral genetic and epigenetic variations have been associated with carcinogenesis for other high-risk HPV types, but little is known about HPV31. We sequenced 2093 HPV31 viral whole genomes from two large studies, one from the U.S. and one international. In addition, we investigated CpG methylation in a subset of 175 samples. We evaluated the association of HPV31 lineages/sublineages, single nucleotide polymorphisms (SNPs) and viral methylation with cervical carcinogenesis. HPV31 A/B clade was >1.8-fold more associated with cervical intraepithelial neoplasia grade 3 and cancer (CIN3+) compared to the most common C lineage. Lineage/sublineage distribution varied by race/ethnicity and geographic region. A viral genome-wide association analysis identified SNPs within the A/B clade associated with CIN3+, including H23Y (C626T) (odds ratio = 1.60, confidence intervals = 1.17–2.19) located in the pRb CR2 binding-site within the E7 oncogene. Viral CpG methylation was higher in lineage B, compared to the other lineages, and was most elevated in CIN3+. In conclusion, these data support the increased oncogenicity of the A/B lineages and suggest variation of E7 as a contributing risk factor.