Phylogenomic Analysis of Human Papillomavirus Type 31 and Cervical Carcinogenesis: A Study of 2093 Viral Genomes

Autor: 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
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Viruses, Vol 13, Iss 10, p 1948 (2021)
Druh dokumentu: article
ISSN: 1999-4915
DOI: 10.3390/v13101948
Popis: 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.
Databáze: Directory of Open Access Journals