Evidence map›Paper›PMID 39686532›Full record

ArticleInternational journal of cancer2025

Colposcopy referrals and CIN3 detection after triage by host cell DNA methylation and/or HPV genotyping in HPV positive women with low-grade cytology from a population-based Dutch primary HPV screening trial.

Lisanne Verhoef, Maaike C G Bleeker, Nicole Polman, Kelsi R Kroon, Renske D M Steenbergen, Renée M F Ebisch, Willem J G Melchers, Ruud L M Bekkers, Anco C Molijn, Folkert van Kemenade and 3 more

Abstract read
In one paragraph

Article in International journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Frontiers in medicine · 2025
    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

13 authors.

Lisanne VerhoefAmsterdam UMC, location Vrije Universiteit Amsterdam, Pathology, Amsterdam, The Netherlands.ORCID 0000-0001-9877-0297
Maaike C G BleekerAmsterdam UMC, location Vrije Universiteit Amsterdam, Pathology, Amsterdam, The Netherlands.
Nicole PolmanAmsterdam UMC, location Vrije Universiteit Amsterdam, Pathology, Amsterdam, The Netherlands.
Kelsi R KroonAmsterdam UMC, location Vrije Universiteit Amsterdam, Epidemiology and Data Science, Amsterdam, The Netherlands.ORCID 0009-0005-7546-4410
Renske D M SteenbergenAmsterdam UMC, location Vrije Universiteit Amsterdam, Pathology, Amsterdam, The Netherlands.ORCID 0000-0002-2327-9839
Renée M F EbischRadboud University Medical Center, Obstetrics and Gynecology, Nijmegen, The Netherlands.ORCID 0000-0002-3422-5086
Willem J G MelchersRadboud University Medical Center, Medical Microbiology, Nijmegen, The Netherlands.
Ruud L M BekkersRadboud University Medical Center, Obstetrics and Gynecology, Nijmegen, The Netherlands.ORCID 0000-0002-4577-8495
Anco C MolijnEurofins NMDL-LCPL, Rijswijk, The Netherlands.
Folkert van KemenadeErasmus MC University Medical Center, Department of Pathology, Rotterdam, The Netherlands.
Chris J L M MeijerAmsterdam UMC, location Vrije Universiteit Amsterdam, Pathology, Amsterdam, The Netherlands.
Daniëlle A M HeidemanAmsterdam UMC, location Vrije Universiteit Amsterdam, Pathology, Amsterdam, The Netherlands.
Johannes BerkhofAmsterdam UMC, location Vrije Universiteit Amsterdam, Epidemiology and Data Science, Amsterdam, The Netherlands.ORCID 0000-0003-2094-2380

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

High-risk HPV (hrHPV)-based screening has led to many unnecessary colposcopy referrals, mainly because of direct referral after low-grade cytology (ASC-US/LSIL). DNA methylation and genotyping tests on ASC-US/LSIL samples have the potential to significantly improve the efficiency of screening. In this study, 12 triage strategies were constructed from FAM19A4/miR124-2 or ASCL1/LHX8 methylation, HPV16/18 or HPV16/18/31/33/45 genotyping and 1-year repeat cytology. The performance was evaluated on 215 hrHPV-positive ASC-US/LSIL samples from the IMPROVE trial (NTR5078). Performance was measured by colposcopy referral rate, positive predictive value (PPV) for detecting precancer (CIN3), and negative predictive value (NPV). To evaluate efficiency, strategies were ordered by the cumulative colposcopy referral rate after 1-year cytology and compared by the marginal PPV to detect one additional CIN3 (mPPV). The most conservative strategy (referral when HPV16/18 and FAM19A4/miR124 methylation results are positive) had a direct referral rate of 5.2%, a cumulative referral rate after 1-year cytology of 54.1%, and mPPV of 19.3%. Replacing HPV16/18 by HPV16/18/31/33/45 increased the cumulative 1-year referral rate to 54.6%, and yielded an mPPV of 10.0%. Similar results were obtained for strategies with ASCL1/LHX8 methylation. Of all strategies, referral after an HPV16/18/31/33/45 positive, ASCL1/LHX8 methylation-positive, and/or 1-year cytology-positive result yielded the highest direct and cumulative 1-year colposcopy referral rates of 64.4% and 79.1%, respectively. The NPVs after 1-year cytology varied between 98.1% and 99.4%, warranting a return to routine screening. Altogether, DNA methylation-based triage strategies are recommended as they are discriminative for CIN3 and control the number of immediate colposcopy referrals.

Indexed as

ColposcopyDNA MethylationEarly Detection of CancerPapillomavirus InfectionsReferral and ConsultationTriageUterine Cervical DysplasiaUterine Cervical NeoplasmsAdultCytokinesFemaleGenotypeHumansMicroRNAsMiddle AgedNetherlandsCytokinesMicroRNAsMIRN124 microRNA, humanTAFA4 protein, humanASC‐US/LSILcervical cancercolposcopy referralsdiagnostic markersDNA methylation

Identifiers

PMID39686532
PMCPMC11701402

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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.