{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T01:36:04Z","timestamp":1782437764421,"version":"3.54.5"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,9,19]],"date-time":"2014-09-19T00:00:00Z","timestamp":1411084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CRN-83320"],"award-info":[{"award-number":["CRN-83320"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-42532"],"award-info":[{"award-number":["MOP-42532"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C569\/A10404"],"award-info":[{"award-number":["C569\/A10404"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:p>\n                    Methylation of human papillomavirus (HPV) and host genes may predict cervical cancer risk. We examined the methylation status of selected sites in HPV16 and human genes in DNA extracted from exfoliated cervical cell samples of 244 women harboring HPV16\u2010positive cancer or cervical intraepithelial neoplasia (CIN) or negative for intraepithelial lesions or malignancy (NILM). We quantified the methylation of CpG sites in the HPV16 L1 gene (CpG 6367 and 6389) and in the human genes\n                    <jats:italic>EPB41L3<\/jats:italic>\n                    (CpG 438, 427, 425) and\n                    <jats:italic>LMX1<\/jats:italic>\n                    (CpG 260, 262, 266, 274) following bisulfite treatment and pyrosequencing. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic utility of methylation level for the different sites and for a joint predictor score. Methylation in all sites significantly increased with lesion severity (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Area under the curve (AUC) was highest among the CIN2\/3\n                    <jats:italic>vs<\/jats:italic>\n                    . cancer ranging from 0.786 to 0.853 among the different sites. Site\u2010specific methylation levels strongly discriminated CIN2\/3 from NILM\/CIN1 and cancer from CIN2\/3 (range of odds ratios [OR]: 3.69\u201312.76, range of lower 95% confidence bounds: 1.03\u20134.01). When methylation levels were mutually adjusted for each other\n                    <jats:italic>EPB41L3<\/jats:italic>\n                    was the only independent predictor of CIN2\/3\n                    <jats:italic>vs<\/jats:italic>\n                    . NILM\/CIN1 contrasts (OR\u2009=\u20099.94, 95%CI: 2.46\u201340.27). High methylation levels of viral and host genes are common among precancerous and cancer lesions and can serve as independent risk biomarkers. Methylation of host genes\n                    <jats:italic>LMX1<\/jats:italic>\n                    and\n                    <jats:italic>EPB41L3<\/jats:italic>\n                    and of the viral HPV16 L1 sites has the potential to distinguish among precancerous lesions and to distinguish the latter from invasive disease.\n                  <\/jats:p>","DOI":"10.1002\/ijc.29196","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T06:07:39Z","timestamp":1410847659000},"source":"Crossref","is-referenced-by-count":53,"title":["Methylation of viral and host genes and severity of cervical lesions associated with human papillomavirus type 16"],"prefix":"10.1002","volume":"136","author":[{"given":"Karolina","family":"Louvanto","sequence":"first","affiliation":[{"name":"Department of Oncology Division of Cancer Epidemiology McGill University Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo L.","family":"Franco","sequence":"additional","affiliation":[{"name":"Department of Oncology Division of Cancer Epidemiology McGill University Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnihotram V.","family":"Ramanakumar","sequence":"additional","affiliation":[{"name":"Department of Oncology Division of Cancer Epidemiology McGill University Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nata\u0161a","family":"Vasiljevi\u0107","sequence":"additional","affiliation":[{"name":"Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine, Queen Mary University of London Charterhouse Square London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Scibior\u2010Bentkowska","sequence":"additional","affiliation":[{"name":"Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine, Queen Mary University of London Charterhouse Square London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Koushik","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie M\u00e9dicale et Infectiologie Centre de recherche du centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al (CHUM) 1560 Sherbrooke est Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Cuzick","sequence":"additional","affiliation":[{"name":"Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine, Queen Mary University of London Charterhouse Square London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Coutl\u00e9e","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie M\u00e9dicale et Infectiologie Centre de recherche du centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al (CHUM) 1560 Sherbrooke est Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila T.","family":"Lorincz","sequence":"additional","affiliation":[{"name":"Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine, Queen Mary University of London Charterhouse Square London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Biomarkers of Cervical Cancer Risk Study 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