Evidence map›Paper›PMID 31616037›Full record

SynthesisBritish journal of cancer2019

Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia (CIN2+): a systematic review and meta-analysis.

Helen Kelly, Yolanda Benavente, Miquel Angel Pavon, Silvia De Sanjose, Philippe Mayaud, Attila Tibor Lorincz

Open access · hybridAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 3 pooled it
9.6field-weighted citation impact, top 1% 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

71 citing papers in PubMed, 3 syntheses or guidelines pooled it, 143 citations in OpenAlex.

  1. Pooled it
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  6. Review
  7. PAX1 and ZNF582 Methylation as a Triage Strategy in Cytologic and hrHPV+ Scrapings in Both Chinese and Dutch Cohorts.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026
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  17. Epigenetic Biomarkers for Cervical Cancer Progression: A Scoping Review.International journal of molecular sciences · 2025
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11 more citing papers are in PubMed but not listed here.

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

6 authors at 5 institutions in 3 countries.

Helen KellyCancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, CIBER-ONC, L'Hospitalet de Llobregat, Barcelona, Spain. helen.kelly@lshtm.ac.uk.ORCID http://orcid.org/0000-0001-5547-3807
Yolanda BenaventeCIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
Miquel Angel PavonCancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, CIBER-ONC, L'Hospitalet de Llobregat, Barcelona, Spain.
Silvia De SanjoseCIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
Philippe MayaudLondon School of Hygiene and Tropical Medicine, London, UK.
Attila Tibor LorinczQueen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts & the London School of Medicine, London, UK.
Institut d'Investigació Biomédica de Bellvitge · ESCentro de Investigación Biomédica en Red de Epidemiología y Salud Pública · ESLondon School of Hygiene & Tropical Medicine · GBProgram for Appropriate Technology in Health · USQueen Mary University of London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTo conduct a meta-analysis of performance of DNA methylation in women with high-grade cervical intraepithelial neoplasia (CIN2+).

methodsMedline and Embase databases were searched for studies of methylation markers versus histological endpoints. Pooled sensitivity, specificity and positive predictive value (PPV) for CIN2+ were derived from bivariate models. Relative sensitivity and specificity for CIN2+ compared to cytology and HPV16/18 genotyping were pooled using random-effects models.

resultsSixteen thousand three hundred thirty-six women in 43 studies provided data on human genes (CADM1, MAL, MIR-124-2, FAM19A4, POU4F3, EPB41L3, PAX1, SOX1) and HPV16 (L1/L2). Most (81%) studies evaluated methylation assays following a high-risk (HR)-HPV-positive or abnormal cytology result. Pooled CIN2+ and CIN3+ prevalence was 36.7% and 21.5%. For a set specificity of 70%, methylation sensitivity for CIN2+ and CIN3+ were 68.6% (95% CI: 62.9-73.8) and 71.1% (95% CI: 65.7-76.0) and PPV were 53.4% (95% CI: 44.4-62.1) and 35.0% (95% CI: 28.9-41.6). Among HR-HPV+ women, the relative sensitivity of methylation for CIN2+ was 0.81 (95% CI: 0.63-1.04) and 1.22 (95% CI: 1.05-1.42) compared to cytology of atypical squamous cells of undetermined significance, or greater (ASCUS+) and HPV16/18 genotyping, respectively, while relative specificity was 1.25 (95% CI: 0.99-1.59) and 1.03 (95% CI: 0.94-1.13), respectively.

conclusionDNA methylation is significantly higher in CIN2+ and CIN3+ compared to ≤CIN1. As triage test, DNA methylation has higher specificity than cytology ASCUS+ and higher sensitivity than HPV16/18 genotyping.

Indexed as

AdultAgedAged, 80 and overDNA MethylationFemaleGenome, HumanHuman papillomavirus 16Human papillomavirus 18HumansMiddle AgedNeoplasm GradingPapillomavirus InfectionsSensitivity and SpecificityTriageUterine Cervical DysplasiaUterine Cervical Neoplasms

Identifiers

PMID31616037
PMCPMC6889421
OpenAlexW2981289376

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.