Evidence map›Paper›PMID 30079796›Full record

ArticleEpigenetics2018

Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer.

Wina Verlaat, Robert W Van Leeuwen, Putri W Novianti, Ed Schuuring, Chris J L M Meijer, Ate G J Van Der Zee, Peter J F Snijders, Daniëlle A M Heideman, Renske D M Steenbergen, G Bea A Wisman

Open access · hybridAbstract read
In one paragraph

Article in Epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
  2. Observational
  3. How to evaluate and select cervical screening and triage tests in vaccinated populations.Journal of the National Cancer Institute. Monographs · 2026
    Article
  4. Observational
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Advances in cervical cancer: current insights and future directions.Cancer communications (London, England) · 2025
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. 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 at 2 institutions in 1 country.

Wina Verlaata Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology , Cancer Center Amsterdam , Amsterdam , The Netherlands.
Robert W Van Leeuwenb Department of Gynecologic Oncology , University of Groningen, University Medical Center Groningen, Cancer Research Center Groningen , Groningen , The Netherlands.
Putri W Noviantia Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology , Cancer Center Amsterdam , Amsterdam , The Netherlands.
Ed Schuuringc Department of Pathology , University of Groningen, University Medical Center Groningen, Cancer Research Center Groningen , Groningen , The Netherlands.ORCID 0000-0003-3655-143X
Chris J L M Meijera Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology , Cancer Center Amsterdam , Amsterdam , The Netherlands.ORCID 0000-0002-2758-9463
Ate G J Van Der Zeeb Department of Gynecologic Oncology , University of Groningen, University Medical Center Groningen, Cancer Research Center Groningen , Groningen , The Netherlands.ORCID 0000-0002-2903-9684
Peter J F Snijdersa Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology , Cancer Center Amsterdam , Amsterdam , The Netherlands.ORCID 0000-0002-3064-3002
Daniëlle A M Heidemana Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology , Cancer Center Amsterdam , Amsterdam , The Netherlands.ORCID 0000-0001-6463-7391
Renske D M Steenbergena Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology , Cancer Center Amsterdam , Amsterdam , The Netherlands.ORCID 0000-0002-2327-9839
G Bea A Wismanb Department of Gynecologic Oncology , University of Groningen, University Medical Center Groningen, Cancer Research Center Groningen , Groningen , The Netherlands.ORCID 0000-0002-4830-3401
Amsterdam University Medical Centers · NLUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cervical cancer development following a persistent infection with high-risk human papillomavirus (hrHPV) is driven by additional host-cell changes, such as altered DNA methylation. In previous studies, we have identified 12 methylated host genes associated with cervical cancer and pre-cancer (CIN2/3). This study systematically analyzed the onset and DNA methylation pattern of these genes during hrHPV-induced carcinogenesis using a longitudinal in vitro model of hrHPV-transformed cell lines (n = 14) and hrHPV-positive cervical scrapings (n = 113) covering various stages of cervical carcinogenesis. DNA methylation analysis was performed by quantitative methylation-specific PCR (qMSP) and relative qMSP values were used to analyze the data. The majority of genes displayed a comparable DNA methylation pattern in both cell lines and clinical specimens. DNA methylation onset occurred at early or late immortal passage, and DNA methylation levels gradually increased towards tumorigenic cells. Subsequently, we defined a so-called cancer-like methylation-high pattern based on the DNA methylation levels observed in cervical scrapings from women with cervical cancer. This cancer-like methylation-high pattern was observed in 72% (38/53) of CIN3 and 55% (11/20) of CIN2, whereas it was virtually absent in hrHPV-positive controls (1/26). In conclusion, hrHPV-induced carcinogenesis is characterized by early onset of DNA methylation, typically occurring at the pre-tumorigenic stage and with highest DNA methylation levels at the cancer stage. Host-cell DNA methylation patterns in cervical scrapings from women with CIN2 and CIN3 are heterogeneous, with a subset displaying a cancer-like methylation-high pattern, suggestive for a higher cancer risk.

Indexed as

DNA MethylationCarcinogenesisFemaleHumansPapillomaviridaePapillomavirus InfectionsPrecancerous ConditionsTumor Cells, CulturedUterine Cervical DysplasiaUterine Cervical NeoplasmsCervical carcinogenesiscervical scrapingsDNA methylation markersepigeneticshrHPVin vitro modelquantitative methylation-specific PCR (qMSP)

Identifiers

PMID30079796
PMCPMC6224221
OpenAlexW2887851388

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.