Evidence map›Paper›PMID 19443004›Full record

ArticleVirology2009

Distinct human papillomavirus type 16 methylomes in cervical cells at different stages of premalignancy.

Janet L Brandsma, Ying Sun, Paul M Lizardi, David P Tuck, Daniel Zelterman, G Kenneth Haines, Maritza Martel, Malini Harigopal, Kevin Schofield, Matthew Neapolitano

Abstract read
In one paragraph

Article in Virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
–field-weighted citation impact
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

45 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Methylation of High-Risk Human Papillomavirus Genomes Are Associated with Cervical Precancer in HIV-Positive Women.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2018
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
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  16. Article
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Janet L BrandsmaSection of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. janet.brandsma@yale.edu
Ying Sun
Paul M Lizardi
David P Tuck
Daniel Zelterman
G Kenneth Haines
Maritza Martel
Malini Harigopal
Kevin Schofield
Matthew Neapolitano

Funding

Yale Center of Excellence in Molecular HematologyP30DK072442 · NIDDK · YALE UNIVERSITY · PI KRAUSE, DIANE S · 2005 to 2010
$5.2M
NIDDK NIH HHS DK072442NIDDK NIH HHS P30 DK072442
6 · The paper itself

Abstract

Human papillomavirus (HPV) gene expression is dramatically altered during cervical carcinogenesis. Because dysregulated genes frequently show abnormal patterns of DNA methylation, we hypothesized that comprehensive mapping of the HPV methylomes in cervical samples at different stages of progression would reveal patterns of clinical significance. To test this hypothesis, thirteen HPV16-positive samples were obtained from women undergoing routine cervical cancer screening. Complete methylation data were obtained for 98.7% of the HPV16 CpGs in all samples by bisulfite-sequencing. Most HPV16 CpGs were unmethylated or methylated in only one sample. The other CpGs were methylated at levels ranging from 11% to 100% of the HPV16 copies per sample. The results showed three major patterns and two variants of one pattern. The patterns showed minimal or no methylation (A), low level methylation in the E1 and E6 genes (B), and high level methylation at many CpGs in the E5/L2/L1 region (C). Generally, pattern A was associated with negative cytology, pattern B with low-grade lesions, and pattern C with high-grade lesions. The severity of the cervical lesions was then ranked by the HPV16 DNA methylation patterns and, independently, by the pathologic diagnoses. Statistical analysis of the two rating methods showed highly significant agreement. In conclusion, analysis of the HPV16 DNA methylomes in clinical samples of cervical cells led to the identification of distinct methylation patterns which, after validation in larger studies, could have potential utility as biomarkers of neoplastic cervical progression.

Indexed as

DNA MethylationBiomarkersCluster AnalysisCpG IslandsDNA, ViralFemaleGene Expression Regulation, ViralHuman papillomavirus 16HumansPapillomavirus InfectionsPolymerase Chain ReactionPrecancerous ConditionsSensitivity and SpecificityUterine Cervical NeoplasmsBiomarkersDNA, Viral

Identifiers

PMID19443004
PMCPMC2918277

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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.