HPV16 Sublineage Associations with Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women

Lisa Mirabello, Meredith Yeager, Michael Cullen, Joseph F. Boland, Zigui Chen, Nicolas Wentzensen, Xijun Zhang, Kai Yu, Qi Yang, Jason Mitchell, David Roberson, Sara Bass, Yanzi Xiao, Laurie Burdett, Tina Raine-Bennett, Thomas Lorey, Philip E. Castle, Robert D. Burk, Mark Schiffman

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: HPV16 is a common sexually transmitted infection although few infections lead to cervical precancer/cancer; we cannot distinguish nor mechanistically explain why only certain infections progress. HPV16 can be classified into four main evolutionary-derived variant lineages (A, B, C, D) that have been previously suggested to have varying disease risks. Methods: We used a high-throughput HPV16 whole-genome sequencing assay to investigate variant lineage risk among 3215 HPV16-infected women. Using sublineages A1/A2 as the reference, we assessed all variant lineage associations with infection outcome over three or more years of follow-up: 1107 control subjects (<CIN2), 906 CIN2, 1008 CIN3, 69 squamous cell carcinomas (SCC), 85 adenocarcinomas in situ (AIS), and 40 adenocarcinomas. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: A4 sublineage was associated with an increased risk of cancer, specifically adenocarcinoma (OR = 9.81, 95% CI = 2.02 to 47.69, P = 4.7x10-03). Lineage B had a lower risk of CIN3 (OR = 0.51, 95% CI = 0. 28 to 0.91, P =. 02) while lineage C showed increased risk (OR = 2.06, 95% CI = 1.09 to 3.89, P =. 03). D2/D3 sublineages were strongly associated with an increased risk of CIN3 and cancer, particularly D2 (OR for cancer = 28.48, 95% CI = 9.27 to 87.55, P = 5.0x10-09). D2 had the strongest increased risk of glandular lesions, AIS (OR = 29.22, 95% CI = 8.94 to 95.51, P = 2.3x10-08), and adenocarcinomas (OR = 137.34, 95% CI = 37.21 to 506.88, P = 1.5x10-13). Moreover, the risk of precancer and cancer for specific variant lineages varied by a women's race/ethnicity; those women whose race/ethnicity matched that of the infecting HPV16 variant had an increased risk of CIN3 + (P <. 001). Conclusions: Specific HPV16 variant sublineages strongly influence risk of histologic types of precancer and cancer, and viral genetic variation may help explain its unique carcinogenic properties.

Original languageEnglish (US)
Article numberdjw100
JournalJournal of the National Cancer Institute
Volume108
Issue number9
DOIs
StatePublished - Sep 1 2016

Fingerprint

Histology
Genome
Odds Ratio
Confidence Intervals
Neoplasms
Adenocarcinoma
Infection
Logistic Models
Sexually Transmitted Diseases
varespladib methyl
Uterine Cervical Neoplasms
Squamous Cell Carcinoma

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Mirabello, L., Yeager, M., Cullen, M., Boland, J. F., Chen, Z., Wentzensen, N., ... Schiffman, M. (2016). HPV16 Sublineage Associations with Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women. Journal of the National Cancer Institute, 108(9), [djw100]. https://doi.org/10.1093/jnci/djw100

HPV16 Sublineage Associations with Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women. / Mirabello, Lisa; Yeager, Meredith; Cullen, Michael; Boland, Joseph F.; Chen, Zigui; Wentzensen, Nicolas; Zhang, Xijun; Yu, Kai; Yang, Qi; Mitchell, Jason; Roberson, David; Bass, Sara; Xiao, Yanzi; Burdett, Laurie; Raine-Bennett, Tina; Lorey, Thomas; Castle, Philip E.; Burk, Robert D.; Schiffman, Mark.

In: Journal of the National Cancer Institute, Vol. 108, No. 9, djw100, 01.09.2016.

Research output: Contribution to journalArticle

Mirabello, L, Yeager, M, Cullen, M, Boland, JF, Chen, Z, Wentzensen, N, Zhang, X, Yu, K, Yang, Q, Mitchell, J, Roberson, D, Bass, S, Xiao, Y, Burdett, L, Raine-Bennett, T, Lorey, T, Castle, PE, Burk, RD & Schiffman, M 2016, 'HPV16 Sublineage Associations with Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women', Journal of the National Cancer Institute, vol. 108, no. 9, djw100. https://doi.org/10.1093/jnci/djw100
Mirabello, Lisa ; Yeager, Meredith ; Cullen, Michael ; Boland, Joseph F. ; Chen, Zigui ; Wentzensen, Nicolas ; Zhang, Xijun ; Yu, Kai ; Yang, Qi ; Mitchell, Jason ; Roberson, David ; Bass, Sara ; Xiao, Yanzi ; Burdett, Laurie ; Raine-Bennett, Tina ; Lorey, Thomas ; Castle, Philip E. ; Burk, Robert D. ; Schiffman, Mark. / HPV16 Sublineage Associations with Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women. In: Journal of the National Cancer Institute. 2016 ; Vol. 108, No. 9.
@article{80283523073c4243bc04b64cdf5b299e,
title = "HPV16 Sublineage Associations with Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women",
abstract = "Background: HPV16 is a common sexually transmitted infection although few infections lead to cervical precancer/cancer; we cannot distinguish nor mechanistically explain why only certain infections progress. HPV16 can be classified into four main evolutionary-derived variant lineages (A, B, C, D) that have been previously suggested to have varying disease risks. Methods: We used a high-throughput HPV16 whole-genome sequencing assay to investigate variant lineage risk among 3215 HPV16-infected women. Using sublineages A1/A2 as the reference, we assessed all variant lineage associations with infection outcome over three or more years of follow-up: 1107 control subjects (<CIN2), 906 CIN2, 1008 CIN3, 69 squamous cell carcinomas (SCC), 85 adenocarcinomas in situ (AIS), and 40 adenocarcinomas. Logistic regression models were used to estimate odds ratios (ORs) and 95{\%} confidence intervals (CIs). All statistical tests were two-sided. Results: A4 sublineage was associated with an increased risk of cancer, specifically adenocarcinoma (OR = 9.81, 95{\%} CI = 2.02 to 47.69, P = 4.7x10-03). Lineage B had a lower risk of CIN3 (OR = 0.51, 95{\%} CI = 0. 28 to 0.91, P =. 02) while lineage C showed increased risk (OR = 2.06, 95{\%} CI = 1.09 to 3.89, P =. 03). D2/D3 sublineages were strongly associated with an increased risk of CIN3 and cancer, particularly D2 (OR for cancer = 28.48, 95{\%} CI = 9.27 to 87.55, P = 5.0x10-09). D2 had the strongest increased risk of glandular lesions, AIS (OR = 29.22, 95{\%} CI = 8.94 to 95.51, P = 2.3x10-08), and adenocarcinomas (OR = 137.34, 95{\%} CI = 37.21 to 506.88, P = 1.5x10-13). Moreover, the risk of precancer and cancer for specific variant lineages varied by a women's race/ethnicity; those women whose race/ethnicity matched that of the infecting HPV16 variant had an increased risk of CIN3 + (P <. 001). Conclusions: Specific HPV16 variant sublineages strongly influence risk of histologic types of precancer and cancer, and viral genetic variation may help explain its unique carcinogenic properties.",
author = "Lisa Mirabello and Meredith Yeager and Michael Cullen and Boland, {Joseph F.} and Zigui Chen and Nicolas Wentzensen and Xijun Zhang and Kai Yu and Qi Yang and Jason Mitchell and David Roberson and Sara Bass and Yanzi Xiao and Laurie Burdett and Tina Raine-Bennett and Thomas Lorey and Castle, {Philip E.} and Burk, {Robert D.} and Mark Schiffman",
year = "2016",
month = "9",
day = "1",
doi = "10.1093/jnci/djw100",
language = "English (US)",
volume = "108",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - HPV16 Sublineage Associations with Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women

AU - Mirabello, Lisa

AU - Yeager, Meredith

AU - Cullen, Michael

AU - Boland, Joseph F.

AU - Chen, Zigui

AU - Wentzensen, Nicolas

AU - Zhang, Xijun

AU - Yu, Kai

AU - Yang, Qi

AU - Mitchell, Jason

AU - Roberson, David

AU - Bass, Sara

AU - Xiao, Yanzi

AU - Burdett, Laurie

AU - Raine-Bennett, Tina

AU - Lorey, Thomas

AU - Castle, Philip E.

AU - Burk, Robert D.

AU - Schiffman, Mark

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background: HPV16 is a common sexually transmitted infection although few infections lead to cervical precancer/cancer; we cannot distinguish nor mechanistically explain why only certain infections progress. HPV16 can be classified into four main evolutionary-derived variant lineages (A, B, C, D) that have been previously suggested to have varying disease risks. Methods: We used a high-throughput HPV16 whole-genome sequencing assay to investigate variant lineage risk among 3215 HPV16-infected women. Using sublineages A1/A2 as the reference, we assessed all variant lineage associations with infection outcome over three or more years of follow-up: 1107 control subjects (<CIN2), 906 CIN2, 1008 CIN3, 69 squamous cell carcinomas (SCC), 85 adenocarcinomas in situ (AIS), and 40 adenocarcinomas. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: A4 sublineage was associated with an increased risk of cancer, specifically adenocarcinoma (OR = 9.81, 95% CI = 2.02 to 47.69, P = 4.7x10-03). Lineage B had a lower risk of CIN3 (OR = 0.51, 95% CI = 0. 28 to 0.91, P =. 02) while lineage C showed increased risk (OR = 2.06, 95% CI = 1.09 to 3.89, P =. 03). D2/D3 sublineages were strongly associated with an increased risk of CIN3 and cancer, particularly D2 (OR for cancer = 28.48, 95% CI = 9.27 to 87.55, P = 5.0x10-09). D2 had the strongest increased risk of glandular lesions, AIS (OR = 29.22, 95% CI = 8.94 to 95.51, P = 2.3x10-08), and adenocarcinomas (OR = 137.34, 95% CI = 37.21 to 506.88, P = 1.5x10-13). Moreover, the risk of precancer and cancer for specific variant lineages varied by a women's race/ethnicity; those women whose race/ethnicity matched that of the infecting HPV16 variant had an increased risk of CIN3 + (P <. 001). Conclusions: Specific HPV16 variant sublineages strongly influence risk of histologic types of precancer and cancer, and viral genetic variation may help explain its unique carcinogenic properties.

AB - Background: HPV16 is a common sexually transmitted infection although few infections lead to cervical precancer/cancer; we cannot distinguish nor mechanistically explain why only certain infections progress. HPV16 can be classified into four main evolutionary-derived variant lineages (A, B, C, D) that have been previously suggested to have varying disease risks. Methods: We used a high-throughput HPV16 whole-genome sequencing assay to investigate variant lineage risk among 3215 HPV16-infected women. Using sublineages A1/A2 as the reference, we assessed all variant lineage associations with infection outcome over three or more years of follow-up: 1107 control subjects (<CIN2), 906 CIN2, 1008 CIN3, 69 squamous cell carcinomas (SCC), 85 adenocarcinomas in situ (AIS), and 40 adenocarcinomas. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: A4 sublineage was associated with an increased risk of cancer, specifically adenocarcinoma (OR = 9.81, 95% CI = 2.02 to 47.69, P = 4.7x10-03). Lineage B had a lower risk of CIN3 (OR = 0.51, 95% CI = 0. 28 to 0.91, P =. 02) while lineage C showed increased risk (OR = 2.06, 95% CI = 1.09 to 3.89, P =. 03). D2/D3 sublineages were strongly associated with an increased risk of CIN3 and cancer, particularly D2 (OR for cancer = 28.48, 95% CI = 9.27 to 87.55, P = 5.0x10-09). D2 had the strongest increased risk of glandular lesions, AIS (OR = 29.22, 95% CI = 8.94 to 95.51, P = 2.3x10-08), and adenocarcinomas (OR = 137.34, 95% CI = 37.21 to 506.88, P = 1.5x10-13). Moreover, the risk of precancer and cancer for specific variant lineages varied by a women's race/ethnicity; those women whose race/ethnicity matched that of the infecting HPV16 variant had an increased risk of CIN3 + (P <. 001). Conclusions: Specific HPV16 variant sublineages strongly influence risk of histologic types of precancer and cancer, and viral genetic variation may help explain its unique carcinogenic properties.

UR - http://www.scopus.com/inward/record.url?scp=84989184550&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84989184550&partnerID=8YFLogxK

U2 - 10.1093/jnci/djw100

DO - 10.1093/jnci/djw100

M3 - Article

C2 - 27130930

AN - SCOPUS:84989184550

VL - 108

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 9

M1 - djw100

ER -