Evidence map›Paper›PMID 41275248›Full record

ArticleClinical epigenetics2025

Clinical validation of a three-marker methylation panel to detect CIN3+ in vaginal self-samples in the Dutch population-based screening programme.

Jolien de Waard, Arkajyoti Bhattacharya, Martine T de Boer, Bettien M van Hemel, Martha D Esajas, Karin M Vermeulen, Geertruida H de Bock, Ed Schuuring, G Bea A Wisman

Abstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Observational
  2. Article
  3. 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

9 authors.

Jolien de WaardDepartment of Gynecologic Oncology, Cancer Research Center Groningen, University of Groningen, University Medical Center Groningen, PO-box 30.001, 9700 RB, Groningen, The Netherlands.
Arkajyoti BhattacharyaDepartment of Medical Oncology, Cancer Research Center Groningen, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Martine T de BoerDepartment of Gynecologic Oncology, Cancer Research Center Groningen, University of Groningen, University Medical Center Groningen, PO-box 30.001, 9700 RB, Groningen, The Netherlands.
Bettien M van HemelDepartment of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Martha D EsajasDepartment of Obstetrics and Gynaecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Karin M VermeulenDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Geertruida H de BockDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Ed Schuuring *Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
G Bea A Wisman *Department of Gynecologic Oncology, Cancer Research Center Groningen, University of Groningen, University Medical Center Groningen, PO-box 30.001, 9700 RB, Groningen, The Netherlands. g.b.a.wisman@umcg.nl.

Funding

ZonMw 531002021
6 · The paper itself

Abstract

backgroundThe use of vaginal self-sampling for cervical cancer screening is promising and increasing. However, triage cytology cannot be performed on vaginal self-sampling material after a high-risk human papilloma virus (hrHPV)-positive result. In our recent discovery study, we identified a three-marker panel with high sensitivity (82%) and specificity (74%) for CIN3 or worse (CIN3+). In the present study, we performed the clinical validation of this three-marker panel using real-world hrHPV-positive vaginal self-samples obtained through the Dutch screening programme.

methodsThe markers LHX8, EPB41L3 and ANKRD18CP were analysed using quantitative methylation-specific PCR (QMSP) on a consecutive cohort of hrHPV-positive vaginal self-samples (n = 2482: 408 CIN3+ and 2074 <CIN3). Diagnostic performance was assessed using sensitivity and specificity derived from receiver operating characteristics (ROC) analysis.

resultsThe three-marker panel showed 73% (298/408) sensitivity and 79% (1640/2071) specificity to detect CIN3+, and identified 96% (21/22) of cervical cancer cases. A scenario analysis was performed on a virtual population of 100 000 hrHPV-positive women using vaginal self-sampling, comparing our methylation triage test with current cytology triage testing. This analysis revealed that more cancers (864 vs. 684 or 770 for 80 or 90% uptake) would be detected with our methylation panel, while referral rates (29% vs. 31% for both 80 and 90% uptake) and detection of CIN3 (72% vs. 68 or 77% for 80 or 90% uptake) would be similar for methylation and cytology.

conclusionCompared to cytology triage testing, DNA methylation triage analysis using our three-marker panel offers an appropriate alternative to detect CIN3+ in hrHPV-positive vaginal self-samples. Implementation of the DNA methylation triage test would not only increase cancer detection, but would also eliminate the need for physician visits for cytological triage testing. In addition, it would accelerate referral decisions, ultimately reducing uncertainty and ensuring timely screening completion for all women.

Indexed as

DNA MethylationEarly Detection of CancerUterine Cervical DysplasiaUterine Cervical NeoplasmsAdultAgedBiomarkers, TumorFemaleHumansMass ScreeningMicrofilament ProteinsMiddle AgedNetherlandsPapillomavirus InfectionsSensitivity and SpecificityTranscription FactorsBiomarkers, TumorEPB41L3 protein, humanMicrofilament ProteinsTranscription FactorsCervical cancer screeningCervical intraepithelial neoplasia (CIN)Clinical validationDNA methylationhrHPV-positiveQuantitative methylation-specific PCR (QMSP)Self-sampling

Identifiers

PMID41275248
PMCPMC13202980

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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.