{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T06:45:29Z","timestamp":1759041929338,"version":"3.40.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA142983-02S1","R01CA142983","T32 5T32CA57726-29","F30CA257181"],"award-info":[{"award-number":["R01CA142983-02S1","R01CA142983","T32 5T32CA57726-29","F30CA257181"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CpG site methylation patterns have potential to improve differentiation of high-grade screening-detected cervical abnormalities. We assessed CpG differential methylation (DM) and differential variability (DV) in high-grade (CIN2+) vs low-grade (\u2264 CIN1) lesions. In \u2264 CIN1 (n\u00a0=\u00a0117) and CIN2+ (n\u00a0=\u00a031) samples, cervical sample DNA underwent testing with Illumina HumanMethylation arrays. We assessed DM and DV of CpG methylation M-values among 9 cervical cancer\u2013associated genes. We fit CpG-specific linear models and estimated empirical Bayes standard errors and false discovery rates (FDRs). An exploratory epigenome-wide association study (EWAS) aimed to detect novel DM and DV CpGs (FDR\u00a0&amp;lt;\u00a00.05) and Gene Ontology (GO) term enrichment. Compared to \u2264 CIN1, CIN2+ exhibited greater methylation at CCNA1 cluster 1 (M-value difference 0.24; 95% CI, 0.04-0.43) and RARB cluster 2 (0.16; 95% CI, 0.05-0.28), and lower methylation at CDH1 cluster 1 (\u20130.15; 95% CI, \u20130.26 to \u20130.04). CIN2+ exhibited lower variability at CDH1 cluster 2 (variation difference \u20130.24; 95% CI, \u20130.41 to \u20130.05) and FHIT cluster 1 (\u20130.30; 95% CI, \u20130.50 to \u20130.09). EWAS detected 3534 DM and 270 DV CpGs. Forty-four GO terms were enriched with DM CpGs related to transcriptional, structural, developmental, and neuronal processes. Methylation patterns may help triage screening-detected cervical abnormalities and inform US screening algorithms.<\/jats:p>\n               <jats:p>This article is part of a Special Collection on Gynecological Cancer.<\/jats:p>","DOI":"10.1093\/aje\/kwae254","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T19:38:19Z","timestamp":1723059499000},"page":"1012-1022","source":"Crossref","is-referenced-by-count":2,"title":["Epigenome-wide differential methylation and differential variability as predictors of high-grade cervical intraepithelial neoplasia (CIN2+)"],"prefix":"10.1093","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7634-7340","authenticated-orcid":false,"given":"Alexandra","family":"Bukowski","sequence":"first","affiliation":[{"name":"Department of Epidemiology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599 ,","place":["United 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R","family":"Kosorok","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy R","family":"Brewster","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599 ,","place":["United States"]},{"name":"Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel L","family":"Maguire","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University , Raleigh, NC 27695 ,","place":["United States"]},{"name":"Department of Obstetrics and Gynecology, Duke University Medical Center , Durham, NC 27701 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan K","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Duke University Medical Center , Durham, NC 27701 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Belinda","family":"Nedjai","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Preventive Medicine, Queen Mary University London , London ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efthymios","family":"Ladoukakis","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Preventive Medicine, Queen Mary University London , London ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kari E","family":"North","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of North 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