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

  1. Author:
    Pinheiro, Maisa
    Harari, Ariana
    Schiffman, Mark
    Clifford, Gary M [ORCID]
    Chen, Zigui [ORCID]
    Yeager, Meredith [ORCID]
    Cullen,Michael
    Boland, Joseph F
    Raine-Bennett, Tina
    Steinberg, Mia
    Bass, Sara
    Xiao, Yanzi
    Tenet, Vanessa
    Yu, Kai
    Zhu, Bin
    Burdett,Laurie
    Turan, Sevilay
    Lorey, Thomas
    Castle, Philip E
    Wentzensen, Nicolas
    Burk, Robert D [ORCID]
    Mirabello, Lisa

  2. Author Address

    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA., Departments of Pediatrics and Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer (IARC/WHO), 150 cours Albert Thomas, CEDEX 08, 69372 Lyon, France., Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China., Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD 21701, USA., Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA., Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA 94710, USA., Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA., Department of Epidemiology & Population Health, and Obstetrics, Gynecology and Women 39;s Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.,
    1. Year: 2021
    2. Date: Sep 28
    3. Epub Date: 2021 09 28
  2. Journal: Viruses
    1. 13
    2. 10
  4. Type of Article: Article
  5. ISSN: 1999-4915
  1. 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.

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External Sources

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  2. DOI: 10.3390/v13101948
  3. PMID: 34696378
  4. PMCID: PMC8540939
  5. PII : v13101948

Library Notes

  1. Fiscal Year: FY2021-2022
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