Phylogenomic analysis of human papillomavirus type 31 and cervical carcinogenesis: A study of 2093 viral genomes

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

doi:10.3390/v13101948

Phylogenomic analysis of human papillomavirus type 31 and cervical carcinogenesis: A study of 2093 viral genomes

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 WentzensenRobert D. Burk, Lisa Mirabello

Pediatrics

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English (US)
Article number	1948
Journal	Viruses
Volume	13
Issue number	10
DOIs	https://doi.org/10.3390/v13101948
State	Published - Oct 2021

Keywords

Cervical carcinogenesis
HPV31
Viral genomic variation
Viral methylation

ASJC Scopus subject areas

Infectious Diseases
Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/v13101948

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Pinheiro, M., Harari, A., Schiffman, M., Clifford, G. M., Chen, Z., Yeager, M., Cullen, M., Boland, J. F., Raine-Bennett, T., Steinberg, M., Bass, S., Xiao, Y., Tenet, V., Yu, K., Zhu, B., Burdett, L., Turan, S., Lorey, T., Castle, P. E., ... Mirabello, L. (2021). Phylogenomic analysis of human papillomavirus type 31 and cervical carcinogenesis: A study of 2093 viral genomes. Viruses, 13(10), Article 1948. https://doi.org/10.3390/v13101948

Pinheiro, M, Harari, A, Schiffman, M, Clifford, GM, Chen, Z, Yeager, M, Cullen, M, Boland, JF, Raine-Bennett, T, Steinberg, M, Bass, S, Xiao, Y, Tenet, V, Yu, K, Zhu, B, Burdett, L, Turan, S, Lorey, T, Castle, PE, Wentzensen, N, Burk, RD & Mirabello, L 2021, 'Phylogenomic analysis of human papillomavirus type 31 and cervical carcinogenesis: A study of 2093 viral genomes', Viruses, vol. 13, no. 10, 1948. https://doi.org/10.3390/v13101948

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title = "Phylogenomic analysis of human papillomavirus type 31 and cervical carcinogenesis: A study of 2093 viral genomes",

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.",

keywords = "Cervical carcinogenesis, HPV31, Viral genomic variation, Viral methylation",

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

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = oct,

doi = "10.3390/v13101948",

language = "English (US)",

volume = "13",

journal = "Viruses",

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T1 - Phylogenomic analysis of human papillomavirus type 31 and cervical carcinogenesis

T2 - A study of 2093 viral genomes

AU - Pinheiro, Maisa

AU - Harari, Ariana

AU - Schiffman, Mark

AU - Clifford, Gary M.

AU - Chen, Zigui

AU - Yeager, Meredith

AU - Cullen, Michael

AU - Boland, Joseph F.

AU - Raine-Bennett, Tina

AU - Steinberg, Mia

AU - Bass, Sara

AU - Xiao, Yanzi

AU - Tenet, Vanessa

AU - Yu, Kai

AU - Zhu, Bin

AU - Burdett, Laurie

AU - Turan, Sevilay

AU - Lorey, Thomas

AU - Castle, Philip E.

AU - Wentzensen, Nicolas

AU - Burk, Robert D.

AU - Mirabello, Lisa

PY - 2021/10

Y1 - 2021/10

N2 - 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.

AB - 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.

KW - Cervical carcinogenesis

KW - HPV31

KW - Viral genomic variation

KW - Viral methylation

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SN - 1999-4915

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JO - Viruses

JF - Viruses

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M1 - 1948

ER -

Phylogenomic analysis of human papillomavirus type 31 and cervical carcinogenesis: A study of 2093 viral genomes

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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