Evidence map›Paper›PMID 25032730›Full record

ArticleBritish journal of cancer2014

DNA methylation analysis in self-sampled brush material as a triage test in hrHPV-positive women.

A Boers, R P Bosgraaf, R W van Leeuwen, E Schuuring, D A M Heideman, L F A G Massuger, V M J Verhoef, J Bulten, W J G Melchers, A G J van der Zee and 2 more

Open access · hybridAbstract readComparative Study
In one paragraph

Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 3 pooled it
3.4field-weighted citation impact, top 8% 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

44 citing papers in PubMed, 3 syntheses or guidelines pooled it, 70 citations in OpenAlex.

  1. Pooled it
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  10. Cytologic DNA methylation for managing minimally abnormal cervical cancer screening results.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2025
    Article
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  17. Triage performance of PAX1Clinical epigenetics · 2024
    Article
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  20. HighZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023
    Article
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

12 authors at 5 institutions in 2 countries.

A BoersDepartment of Gynaecologic Oncology, Cancer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
R P BosgraafDepartment of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.
R W van LeeuwenDepartment of Gynaecologic Oncology, Cancer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
E SchuuringDepartment of Pathology, Cancer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
D A M HeidemanDepartment of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
L F A G MassugerDepartment of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.
V M J VerhoefDepartment of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
J BultenDepartment of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
W J G MelchersDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
A G J van der ZeeDepartment of Gynaecologic Oncology, Cancer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
R L M BekkersDepartment of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.
G B A WismanDepartment of Gynaecologic Oncology, Cancer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
University Medical Center Groningen · NLRadboud University Nijmegen · NLRadboud University Medical Center · NLAmsterdam UMC Location VUmc · NLVrije Universiteit Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPrimary high-risk human papillomavirus (hrHPV) testing in cervical cancer screening shows relatively low specificity, which makes triage testing necessary. In this study, DNA methylation analysis was compared with cytology for triage testing in hrHPV-positive women. Moreover, feasibility of DNA methylation analysis directly on brush-based self-sampled specimens was assessed.

methodsNon-responding women from population-based screening were invited to self-collect a cervico-vaginal specimen for hrHPV testing; hrHPV-positive women were referred to a physician for triage liquid-based cytology. DNA methylation analysis was performed on 128 hrHPV-positive physician-collected triage samples and 50 matched brush self-samples with QMSP for C13ORF18, EPB41L3, JAM3 and TERT.

resultsIn physician-taken triage material, DNA methylation analysis of JAM3 showed the highest combined specificity (88%) and sensitivity (82%) for detection of CIN3+, whereas cytology showed a specificity of 48% and a sensitivity of 91%. Out of 39 women with abnormal cytology and normal histology (false-positive by cytology), 87% were negative for JAM3 and 90% for C13ORF18 methylation. Agreement between DNA methylation analysis performed directly on the matched self-sampled material and physician-taken samples was 88% for JAM3 (κ=0.75, P<0.001) and 90% for C13ORF18 (κ=0.77; P<0.001).

conclusionsDNA methylation analysis as a triage test in hrHPV-positive women is an attractive alternative to cytology. Furthermore, DNA methylation is feasible directly on brush-based self-samplers and showed good correlation with matched physician-taken samples. Direct molecular triage on self-collected specimens could optimise the screening program, especially for non-responders, as this would eliminate the need for an additional physician-taken scraping for triage testing.

Indexed as

DNA MethylationAdultCell Adhesion MoleculesEarly Detection of CancerFemaleHumansMicrofilament ProteinsMiddle AgedPapillomavirus InfectionsPatient ComplianceRisk FactorsSelf CareSensitivity and SpecificitySpecimen HandlingTelomeraseTriageCell Adhesion MoleculesEPB41L3 protein, humanJAM3 protein, humanMicrofilament ProteinsRUBCNL protein, humanTelomeraseTERT protein, humanTumor Suppressor Proteins

Identifiers

PMID25032730
PMCPMC4453842
OpenAlexW2015961085

What OpenQuestion holds

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LicenceCC BY-NC-SA
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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.