Evidence map›Paper›PMID 34558659›Full record

ArticleInternational journal of cancer2022

Performance of DNA methylation analysis of ASCL1, LHX8, ST6GALNAC5, GHSR, ZIC1 and SST for the triage of HPV-positive women: Results from a Dutch primary HPV-based screening cohort.

Lisanne Verhoef, Maaike C G Bleeker, Nicole Polman, Renske D M Steenbergen, Chris J L M Meijer, Willem J G Melchers, Ruud L Bekkers, Anco C Molijn, Wim G Quint, Folkert J van Kemenade and 2 more

Open access · hybridAbstract read
In one paragraph

Article in International journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
6.8field-weighted citation impact, top 2% 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

25 citing papers in PubMed, 45 citations in OpenAlex.

  1. SOX1/PAX1 Methylation for Triage of HPV-Positive Women in Cervical Cancer Screening: A Cohort Study.BJOG : an international journal of obstetrics and gynaecology · 2026
    Article
  2. Article
  3. Observational
  4. Article
  5. A novel methylation marker on theFrontiers in oncology · 2026
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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 4 institutions in 1 country.

Lisanne VerhoefAmsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0001-9877-0297
Maaike C G BleekerAmsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0001-9610-8064
Nicole PolmanAmsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0001-8216-7098
Renske D M SteenbergenAmsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-2327-9839
Chris J L M MeijerAmsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-2758-9463
Willem J G MelchersRadboud University Medical Center, Medical Microbiology, Nijmegen, The Netherlands.ORCID 0000-0002-5446-2230
Ruud L BekkersGROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.ORCID 0000-0002-4577-8495
Anco C MolijnDDL Diagnostic Laboratory, NMDL-LCPL, Rijswijk, The Netherlands.ORCID 0000-0002-5516-3005
Wim G QuintDDL Diagnostic Laboratory, NMDL-LCPL, Rijswijk, The Netherlands.
Folkert J van KemenadeErasmus MC, University Medical Center, Pathology, Rotterdam, The Netherlands.ORCID 0000-0002-4225-4354
Johannes BerkhofAmsterdam UMC, Vrije Universiteit Amsterdam, Epidemiology and Data Science, Amsterdam, The Netherlands.ORCID 0000-0003-2094-2380
Daniëlle A M HeidemanAmsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0001-6463-7391
Amsterdam University Medical Centers · NLDDL Diagnostic Laboratory · NLRadboud University Nijmegen · NLErasmus MC · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Methylation of host-cell deoxyribonucleic acid (DNA) has been proposed as a promising biomarker for triage of high-risk (hr) human papillomavirus (HPV) positive women at screening. Our study aims to validate recently identified host-cell DNA methylation markers for triage in an hrHPV-positive cohort derived from primary HPV-based cervical screening in The Netherlands. Methylation markers ASCL1, LHX8, ST6GALNAC5, GHSR, ZIC1 and SST were evaluated relative to the ACTB reference gene by multiplex quantitative methylation-specific PCR (qMSP) in clinician-collected cervical samples (n = 715) from hrHPV-positive women (age 29-60 years), who were enrolled in the Dutch IMPROVE screening trial (NTR5078). Primary clinical end-point was cervical intraepithelial neoplasia grade 3 (CIN3) or cancer (CIN3+). The single-marker and bi-marker methylation classifiers developed for CIN3 detection in a previous series of hrHPV-positive clinician-collected cervical samples were applied. The diagnostic accuracy was visualised using receiver operating characteristic (ROC) curves and assessed through area under the ROC curve (AUC). The performance of the methylation markers to detect CIN3+ was determined using the predefined threshold calibrated at 70% clinical specificity. Individual methylation makers showed good performance for CIN3+ detection, with highest AUC for ASCL1 (0.844) and LHX8 (0.830). Combined as a bi-marker panel with predefined threshold, ASCL1/LHX8 yielded a CIN3+ sensitivity of 76.9% (70/91; 95% CI 68.3-85.6%) at a specificity of 74.5% (465/624; 95% CI 71.1-77.9%). In conclusion, our study shows that the individual host-cell DNA methylation classifiers and the bi-marker panel ASCL1/LHX8 have clinical utility for the detection of CIN3+ in hrHPV-positive women invited for routine screening.

Indexed as

DNA MethylationTriageAdultBasic Helix-Loop-Helix ProteinsCohort StudiesFemaleHumansLIM-Homeodomain ProteinsMiddle AgedPapillomaviridaeReceptors, GhrelinSialyltransferasesSomatostatinTranscription FactorsUterine Cervical DysplasiaUterine Cervical NeoplasmsASCL1 protein, humanBasic Helix-Loop-Helix Proteinsbrain-specific GD1alpha synthase, ST6GalNAc VLIM homeobox protein 8LIM-Homeodomain ProteinsReceptors, GhrelinSialyltransferasesSomatostatinTranscription FactorsZIC1 protein, humancervical intraepithelial neoplasiaclinical performancecytologydiagnostic accuracyepigeneticgenotypingprimary HPV screening

Identifiers

PMID34558659
PMCPMC9293097
OpenAlexW3200832879

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.