Evidence map›Paper›PMID 27130930›Full record

ArticleJournal of the National Cancer Institute2016

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 and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 4 pooled it
14.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

131 citing papers in PubMed, 4 syntheses or guidelines pooled it, 202 citations in OpenAlex.

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  13. medRxiv : the preprint server for health sciences · 2026
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71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 1 institution in 2 countries.

Lisa MirabelloDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB) mirabellol@mail.nih.gov.
Meredith YeagerDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Michael CullenDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Joseph F BolandDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Zigui ChenDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Nicolas WentzensenDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Xijun ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Kai YuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Qi YangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Jason MitchellDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
David RobersonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Sara BassDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Yanzi XiaoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Laurie BurdettDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Tina Raine-BennettDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Thomas LoreyDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Philip E CastleDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Robert D BurkDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Mark SchiffmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (LM, MY, MC, JFB, NW, XZ, KY, QY, JM, DR, SB, LB, YX, MS); Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD (MY, MC, JFB, XZ, QY, JM, DR, SB, LB); Department of Microbiology, The Chinese University of Hong Kong, Hong Kong (ZC); Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland CA (TRB); Regional Laboratory, Kaiser Permanente Northern California, Oakland, CA (TL); Department of Epidemiology and Population Health, at Albert Einstein College of Medicine, Bronx, NY (PEC, RDB); Departments of Pediatrics; Microbiology & Immunology; and, Obstetrics, Gynecology and Women's Health, at Albert Einstein College of Medicine, Bronx, NY (RDB).
Chinese University of Hong Kong · HK

Funding

Human Papillomavirus (HPV) Genomics ProjectZIACP010228 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI MIRABELLO, LISA · 2016 to 2025
$9.9M
PERSISTENT HUMAN PAPILLOMAVIRUS IN WOMEN AT RISK FOR CERVIX CANCERU01CA078527 · NCI · YESHIVA UNIVERSITY · PI BURK, ROBERT D · 2003 to 2018
$8.6M
NCI NIH HHS U01 CA078527
6 · The paper itself

Abstract

backgroundHPV16 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.

methodsWe 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.

resultsA4 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).

conclusionsSpecific HPV16 variant sublineages strongly influence risk of histologic types of precancer and cancer, and viral genetic variation may help explain its unique carcinogenic properties.

Indexed as

AdenocarcinomaAdenocarcinoma in SituAdultAftercareCaliforniaCarcinomaCarcinoma, Squamous CellFemaleGenomeHigh-Throughput Nucleotide SequencingHuman papillomavirus 16HumansMiddle AgedPapillomavirus InfectionsPhylogenyPrecancerous Conditions

Identifiers

PMID27130930
PMCPMC5939630
OpenAlexW2344334611

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.