Evidence map›Paper›PMID 31732479›Full record

SynthesisEBioMedicine2019

The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia: A systematic review and meta-analysis.

Sarah J Bowden, Ilkka Kalliala, Areti A Veroniki, Marc Arbyn, Anita Mitra, Kostas Lathouras, Lisa Mirabello, Marc Chadeau-Hyam, Evangelos Paraskevaidis, James M Flanagan and 1 more

Open access · goldAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.

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  15. Triage performance of PAX1Clinical epigenetics · 2024
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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

11 authors at 6 institutions in 5 countries.

Sarah J BowdenDepartment of Surgery and Cancer, 3rd Floor IRDB, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 ONN, London, UK; West London Gynaecology Cancer Centre, Hammersmith Hospital, Imperial Healthcare NHS Trust, UK.
Ilkka KallialaDepartment of Surgery and Cancer, 3rd Floor IRDB, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 ONN, London, UK; Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Finland.
Areti A VeronikiDepartment of Surgery and Cancer, 3rd Floor IRDB, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 ONN, London, UK; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada; Department of Primary Education, School of Education, University of Ioannina, Ioannina, Greece.
Marc ArbynUnit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium.
Anita MitraDepartment of Surgery and Cancer, 3rd Floor IRDB, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 ONN, London, UK; West London Gynaecology Cancer Centre, Hammersmith Hospital, Imperial Healthcare NHS Trust, UK.
Kostas LathourasWest London Gynaecology Cancer Centre, Hammersmith Hospital, Imperial Healthcare NHS Trust, UK.
Lisa MirabelloDepartment of Clinical Genetics, National Institute of Health (NIH), Bethesda, MD, USA.
Marc Chadeau-HyamDepartment of Surgery and Cancer, 3rd Floor IRDB, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 ONN, London, UK.
Evangelos ParaskevaidisDepartment of Obstetrics and Gynaecology, University Hospital of Ioannina, Ioannina, Greece.
James M FlanaganDepartment of Surgery and Cancer, 3rd Floor IRDB, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 ONN, London, UK.
Maria KyrgiouDepartment of Surgery and Cancer, 3rd Floor IRDB, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 ONN, London, UK; West London Gynaecology Cancer Centre, Hammersmith Hospital, Imperial Healthcare NHS Trust, UK. Electronic address: m.kyrgiou@imperial.ac.uk.
Imperial College Healthcare NHS Trust · GBImperial College London · GBInstitut Scientifique de Santé Publique · BESt. Michael's Hospital · CAUniversity Hospital of Ioannina · GRUniversity of Helsinki · FI

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundMethylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus (HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detecting high-grade cervical intra-epithelial neoplasia (CIN).

methodsWe performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women. Data were extracted in duplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effects binary regression model were applied to determine pooled effect estimates.

findings44 studies with 8819 high-risk HPV positive women were eligible. The pooled estimates for positive methylation rate in HPV16 L1 gene were higher for high-grade CIN (≥CIN2/high-grade squamous intra-epithelial lesion (HSIL) (95% confidence interval (95%CI:72·7% (47·8-92·2))) vs. low-grade CIN (≤CIN1/low-grade squamous intra-epithelial lesion (LSIL) (44·4% (95%CI:16·0-74·1))). Pooled difference in mean methylation level was significantly higher in ≥CIN2/HSIL vs. ≤CIN1/LSIL for HPV16 L1 (11·3% (95%CI:6·5-16·1)). Pooled odds ratio of HPV16 L1 methylation was 5·5 (95%CI:3·5-8·5) for ≥CIN2/HSIL vs. ≤CIN1/LSIL (p < 0·0001). HPV16 L1/L2 genes performed best in predicting CIN2 or worse (pooled sensitivity 77% (95%CI:63-87), specificity 64% (95%CI:55-71), area under the curve (0·73 (95%CI:0·69-0·77)).

interpretationHigher HPV methylation is associated with increased disease severity, whilst HPV16 L1/L2 genes demonstrated high diagnostic accuracy to detect high-grade CIN in HPV16 positive women. Direct clinical use is limited by the need for a multi-genotype and standardised assays. Next-generation multiplex HPV sequencing assays are under development and allow potential for rapid, automated and low-cost methylation testing.

fundingNIHR, Genesis Research Trust, Imperial Healthcare Charity, Wellcome Trust NIHR Imperial BRC, European Union's Horizon 2020.

Indexed as

DNA MethylationDNA, ViralCpG IslandsFemaleHuman papillomavirus 16HumansNeoplasm GradingNeoplasm StagingOdds RatioPapillomaviridaePapillomavirus InfectionsROC CurveUterine Cervical DysplasiaDNA, ViralCervical intraepithelial neoplasiaCervical screeningDNA methylationHuman papillomavirusMeta-analysis

Identifiers

PMID31732479
PMCPMC6921230
OpenAlexW2987870876

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.