{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:03:46Z","timestamp":1790291026092,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["322986 Mass\u2010care"],"award-info":[{"award-number":["322986 Mass\u2010care"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["2012\u2010AdG"],"award-info":[{"award-number":["2012\u2010AdG"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2023,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Women treated for <jats:styled-content style=\"fixed-case\">CIN2<\/jats:styled-content>\/3 remain at increased risk of recurrent <jats:styled-content style=\"fixed-case\">CIN<\/jats:styled-content> and cervical cancer, and therefore posttreatment surveillance is recommended. This post hoc analysis evaluates the potential of methylation markers <jats:italic><jats:styled-content style=\"fixed-case\">ASCL1<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">LHX8<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">FAM19A4<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">miR124<\/jats:styled-content>\u20102<\/jats:italic> for posttreatment detection of recurrent <jats:styled-content style=\"fixed-case\">CIN2<\/jats:styled-content>\/3. Cervical scrapes taken at 6 and 12\u2009months posttreatment of 364 women treated for <jats:styled-content style=\"fixed-case\">CIN2<\/jats:styled-content>\/3 were tested for methylation of <jats:italic><jats:styled-content style=\"fixed-case\">ASCL1<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">LHX8<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">FAM19A4<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">miR124<\/jats:styled-content>\u20102<\/jats:italic> using quantitative multiplex methylation\u2010specific <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. Performance of the methylation tests were calculated and compared with the performance of <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> and\/or cytology. Methylation levels of recurrent <jats:styled-content style=\"fixed-case\">CIN<\/jats:styled-content> were compared between women with a persistent <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> infection, and women with an incident <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> infection or without <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> infection. Recurrent <jats:styled-content style=\"fixed-case\">CIN2<\/jats:styled-content>\/3 was detected in 42 women (11.5%), including 28 women with <jats:styled-content style=\"fixed-case\">CIN2<\/jats:styled-content> and 14 with <jats:styled-content style=\"fixed-case\">CIN3<\/jats:styled-content>. <jats:italic><jats:styled-content style=\"fixed-case\">ASCL1<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">LHX8<\/jats:styled-content><\/jats:italic> tested positive in 13\/14 (92.9%) of recurrent <jats:styled-content style=\"fixed-case\">CIN3<\/jats:styled-content> and 13\/27 (48.1%) of recurrent <jats:styled-content style=\"fixed-case\">CIN2<\/jats:styled-content>. <jats:italic><jats:styled-content style=\"fixed-case\">FAM19A4<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">miR124<\/jats:styled-content>\u20102<\/jats:italic> tested positive in 14\/14 (100%) of recurrent <jats:styled-content style=\"fixed-case\">CIN3<\/jats:styled-content> and 10\/27 (37.0%) of recurrent <jats:styled-content style=\"fixed-case\">CIN2<\/jats:styled-content>. Combined <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> and\/or methylation testing showed similar positivity rates as <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> and\/or cytology. The <jats:styled-content style=\"fixed-case\">CIN2<\/jats:styled-content>\/3 risk at 12\u2009months posttreatment was 30.8% after a positive <jats:italic><jats:styled-content style=\"fixed-case\">ASCL1<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">LHX8<\/jats:styled-content><\/jats:italic> result at 6\u2009months posttreatment. Methylation levels of <jats:styled-content style=\"fixed-case\">CIN2<\/jats:styled-content>\/3 in women with a persistent <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> infection were significantly higher compared with women with an incident or no <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> infection. In conclusion, posttreatment monitoring by methylation analysis of <jats:italic><jats:styled-content style=\"fixed-case\">ASCL1<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">LHX8<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">FAM19A4<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">miR124<\/jats:styled-content>\u20102<\/jats:italic> showed a good performance for the detection of recurrent <jats:styled-content style=\"fixed-case\">CIN<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation testing can help to identify women with recurrent <jats:styled-content style=\"fixed-case\">CIN<\/jats:styled-content> that require re\u2010treatment.<\/jats:p>","DOI":"10.1002\/ijc.34678","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T12:22:42Z","timestamp":1691151762000},"page":"2011-2018","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Methylation testing for the detection of recurrent cervical intraepithelial neoplasia"],"prefix":"10.1002","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5548-4557","authenticated-orcid":false,"given":"St\u00e8fanie","family":"Dick","sequence":"first","affiliation":[{"name":"Department of Pathology Amsterdam UMC, Location Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Cancer Center Amsterdam Imaging and Biomarkers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00eblle A. 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