Evidence map›Paper›PMID 37932662›Full record

ArticleBMC cancer2023

Epigenome-wide methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2+): a prospective cohort study in the United States.

Alexandra Bukowski, Cathrine Hoyo, Nadja A Vielot, Misa Graff, Michael R Kosorok, Wendy R Brewster, Rachel L Maguire, Susan K Murphy, Belinda Nedjai, Efthymios Ladoukakis and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
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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 5 institutions in 2 countries.

Alexandra BukowskiDepartment of Epidemiology, University of North Carolina at Chapel Hill, 60 Bondurant Hall, Chapel Hill, NC, 27599, USA. alexandra_bukowski@med.unc.edu.
Cathrine HoyoDepartment of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, 27695, USA.
Nadja A VielotDepartment of Family Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Misa GraffDepartment of Epidemiology, University of North Carolina at Chapel Hill, 60 Bondurant Hall, Chapel Hill, NC, 27599, USA.
Michael R KosorokDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Wendy R BrewsterDepartment of Epidemiology, University of North Carolina at Chapel Hill, 60 Bondurant Hall, Chapel Hill, NC, 27599, USA.
Rachel L MaguireDepartment of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, 27695, USA.
Susan K MurphyDepartment of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, 27701, USA.
Belinda NedjaiCentre for Prevention, Detection and Diagnosis, Wolfson Institute of Population Health, Queen Mary University London, London, UK.
Efthymios LadoukakisCentre for Prevention, Detection and Diagnosis, Wolfson Institute of Population Health, Queen Mary University London, London, UK.
Kari E NorthDepartment of Epidemiology, University of North Carolina at Chapel Hill, 60 Bondurant Hall, Chapel Hill, NC, 27599, USA.
Jennifer S SmithDepartment of Epidemiology, University of North Carolina at Chapel Hill, 60 Bondurant Hall, Chapel Hill, NC, 27599, USA.
University of North Carolina at Chapel Hill · USNorth Carolina State University · USQueen Mary University of London · GBDuke Medical Center · USUNC Lineberger Comprehensive Cancer Center

Funding

Cancer Control Education ProgramT32CA057726 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Melissa B Gilkey, Melissa A. Troester · 2017 to 2026
$3.7M
Disparities in cervical cancer precursors and deregulation of imprinted genesR01CA142983 · NCI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI HOYO, CATHRINE, MURPHY, SUSAN KAY · 2010 to 2014
$3.0M
The effect of epigenetic DNA methylation on the progression of HPV-associated precancerous cervical lesionsF30CA257181 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Alexandra Bukowski · 2021 to 2026
$203k
Cancer Research UK 27046NCI NIH HHS F30 CA257181NCI NIH HHS R01 CA142983NCI NIH HHS T32 CA057726NIH HHS F30CA257181NIH HHS R01CA142983
6 · The paper itself

Abstract

backgroundMethylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test.

methodsA prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05.

resultsAt enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP.

conclusionsUsing prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs. IMPACT: Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines.

Indexed as

Papillomavirus InfectionsUterine Cervical DysplasiaUterine Cervical NeoplasmsAdultCell Adhesion Molecule-1DNA MethylationEarly Detection of CancerEpigenomeFemaleHumansPapillomaviridaeProspective StudiesUnited StatesCADM1 protein, humanCell Adhesion Molecule-1Cancer riskCancer surveillance and screeningCervical cancerDNA methylationEpigeneticsEpigenomicsPre-neoplasia

Identifiers

PMID37932662
PMCPMC10629205
OpenAlexW4388425383

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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.