Evidence map›Paper›PMID 28500655›Full record

ArticleInternational journal of cancer2017

Discovery and validation of candidate host DNA methylation markers for detection of cervical precancer and cancer.

Megan A Clarke, Patricia Luhn, Julia C Gage, Clara Bodelon, S Terence Dunn, Joan Walker, Rosemary Zuna, Stephen Hewitt, J Keith Killian, Liying Yan and 3 more

Abstract read
In one paragraph

Article in International journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 2 pooled it
–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

44 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Article
  6. Review
  7. Review
  8. Identification of a novel hypermethylation marker, ZSCAN18, and construction of a diagnostic model in cervical cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Article
  9. Review
  10. Article
  11. Performance ofBMJ open · 2024
    Observational
  12. Promising predictive molecular biomarkers for cervical cancer (Review).International journal of molecular medicine · 2024
    Review
  13. Article
  14. Review
  15. Article
  16. Methylation-mediated silencing ofFrontiers in oncology · 2023
    Article
  17. Article
  18. Article
  19. Review
  20. Review
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

13 authors.

Megan A ClarkeDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.ORCID 0000-0003-0435-7376
Patricia LuhnGenentech Inc, South San Francisco, CA.
Julia C GageDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
Clara BodelonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
S Terence DunnDepartment of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Joan WalkerDepartment of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Rosemary ZunaDepartment of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Stephen HewittCenter for Cancer Research, National Cancer Institute, Bethesda, MD.
J Keith KillianCenter for Cancer Research, National Cancer Institute, Bethesda, MD.
Liying YanEpigenDx Inc, Hopkinton, MA.
Andrew MillerEpigenDx Inc, Hopkinton, MA.
Mark SchiffmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
Nicolas WentzensenDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.

Funding

Human papillomavirus (HPV) infection and cervical and anal cancersZIACP010124 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI WENTZENSEN, NICOLAS · 2009 to 2025
$17.3M
Intramural NIH HHS ZIA CP010124
6 · The paper itself

Abstract

Human papillomavirus (HPV) testing has been recently introduced as an alternative to cytology for cervical cancer screening. However, since most HPV infections clear without causing clinically relevant lesions, additional triage tests are required to identify women who are at high risk of developing cancer. We performed DNA methylation profiling on formalin-fixed, paraffin-embedded tissue specimens from women with benign HPV16 infection and histologically confirmed cervical intraepithelial neoplasia grade 3, and cancer using a bead-based microarray covering 1,500 CpG sites in over 800 genes. Methylation levels in individual CpG sites were compared using a t-test, and results were summarized by computing p-values. A total of 12 candidate genes (ADCYAP1, ASCL1, ATP10, CADM1, DCC, DBC1, HS3ST2, MOS, MYOD1, SOX1, SOX17 and TMEFF2) identified by DNA methylation profiling, plus an additional three genes identified from the literature (EPB41L3, MAL and miR-124) were chosen for validation in an independent set of 167 liquid-based cytology specimens using pyrosequencing and targeted, next-generation bisulfite sequencing. Of the 15 candidate gene markers, 10 had an area under the curve (AUC) of ≥ 0.75 for discrimination of high grade squamous intraepithelial lesions or worse (HSIL+) from <HSIL cytology using at least one assay. Overall, SOX1, DCC, and EPB41L3 showed the best discrimination with AUC values of ≥0.80, irrespective of methylation detection assay. In addition to verifying candidate markers from the literature (e.g., SOX1 and EPB41L3), we identified novel markers that may be considered for detection of cervical precancer and cancer and warrant further validation in prospective studies.

Indexed as

DNA MethylationAdultAgedArea Under CurveBiomarkers, TumorCpG IslandsEarly Detection of CancerFemaleHuman papillomavirus 16HumansMiddle AgedOligonucleotide Array Sequence AnalysisPapillomavirus InfectionsProspective StudiesSequence Analysis, DNAUterine Cervical DysplasiaBiomarkers, Tumorcervical cancerhuman papillomavirusmethylationnext-generation sequencingpyrosequencing

Identifiers

PMID28500655
PMCPMC6774256

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.