Evidence map›Paper›PMID 42373539›Full record

Observational studyInternational journal of cancer2026

Triage Performance of FAM19A4/miR124-2 Methylation: 18-Month Follow-Up Results From a Prospective Observational Study Within the Dutch Primary HPV-Based Cervical Screening Program.

Lisanne Verhoef, Mila S Griffioen, Maaike C G Bleeker, John W J Hinrichs, Albert G Siebers, Albertus T Hesselink, Chris J L M Meijer, Renske D M Steenbergen, Johannes Berkhof, Daniëlle A M Heideman

Abstract readObservational Study
In one paragraph

Observational study in International journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Lisanne VerhoefPathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Mila S GriffioenPathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.ORCID https://orcid.org/0009-0000-9974-543X
Maaike C G BleekerPathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
John W J HinrichsSymbiant Pathology, Hoorn, the Netherlands.
Albert G SiebersPalga Foundation: The Dutch Nationwide Pathology Databank, Houten, the Netherlands.
Albertus T HesselinkSelf-Screen B.V., Amsterdam, the Netherlands.ORCID https://orcid.org/0000-0002-4282-4417
Chris J L M MeijerSelf-Screen B.V., Amsterdam, the Netherlands.
Renske D M SteenbergenPathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.ORCID https://orcid.org/0000-0002-2327-9839
Johannes BerkhofEpidemiology and Data Science, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Daniëlle A M HeidemanDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Funding

European Commission 847845Nederlandse Organisatie voor Wetenschappelijk Onderzoek-KWF Kankerbestrijding KICH2.V4P.22.017
6 · The paper itself

Abstract

DNA methylation analysis of the genes FAM19A4 and miR124-2 has emerged as a promising triage strategy for high-risk (hr) human papillomavirus (HPV)-positive women in cervical screening. This study reports a prospective evaluation of the diagnostic accuracy of FAM19A4/miR124-2 methylation in a large population-based primary HPV-based screening cohort with 18 months of follow-up. In this prospective observational study, clinician-collected cervical samples from 3848 consecutive hrHPV-positive women who participated in the Dutch national primary HPV-based screening program were tested with the QIAsure Methylation Test, a quantitative methylation-specific PCR assessing FAM19A4 and miR124-2 methylation. Through linkage to the Dutch Nationwide Pathology Databank (Palga), 11 cases of cervical carcinoma, 293 cervical intraepithelial neoplasia grade 3 (CIN3), and 29 adenocarcinoma in situ (AIS) were identified during 18 months of follow-up. Clinical performance for CIN3, AIS, and cancer (CIN3+) detection was assessed based on (I) the threshold of the QIAsure Methylation Test, and (II) thresholds corresponding with clinical specificities of 70% and 80% in this hrHPV-positive study population. The sensitivity and specificity of FAM19A4/miR124-2 methylation for CIN3+ detection using the QIAsure Methylation Test threshold (I) were 57.4% (95% CI: 52.0-62.7) and 88.3% (95% CI: 87.2-89.5), respectively. At predefined specificities of 70% and 80%, FAM19A4/miR124-2 methylation (II) demonstrated a CIN3+ sensitivity of 75.4% (95% CI: 70.7-80.0) and 66.1% (95% CI: 61.0-71.2), respectively. In conclusion, FAM19A4/miR124-2 methylation analysis showed good triage performance in a primary HPV-based screening setting. These findings support the use of methylation-based testing as a triage strategy in primary HPV-based screening programs, with an appropriate follow-up policy for hrHPV-positive women who test methylation-negative.

Indexed as

CytokinesDNA MethylationMicroRNAsPapillomavirus InfectionsUterine Cervical DysplasiaUterine Cervical NeoplasmsAdultEarly Detection of CancerFemaleFollow-Up StudiesHuman Papillomavirus VirusesHumansMiddle AgedNetherlandsProspective StudiesSensitivity and SpecificityCytokinesMicroRNAsMIRN124-2 microRNA, humanTAFA4 protein, humancervical cancercervical intraepithelial neoplasiacervical screening: human papillomavirusDNA methylation

Identifiers

PMID42373539
PMCPMC13595475

What OpenQuestion holds

Textmetadata
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.