{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:30:41Z","timestamp":1780479041735,"version":"3.54.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009780","name":"Region Sk\u00e5ne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Obstet Gynecol Scand"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Methylation analysis of the promoter region of tumor\u2010suppressor genes has previously shown high sensitivity for detection of high\u2010grade cervical intraepithelial neoplasia (CIN) and cancer. HPV\u2010testing has a high sensitivity to identify women at risk to develop cancer, and has been implemented in cervical screening programs in several countries. But in most HPV\u2010positive women the infection will clear and they will not develop cancer. Testing for methylation could help to identify women who have potentially progressive cervical disease and need closer follow\u2010up. The goal of the present study was to investigate the potential use of methylation as a triage test of HPV\u2010positive women in the screening program.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>A collection of liquid\u2010based cytology (LBC) samples from 106 women, collected between 4\u2009months and 8\u2009years before histologically confirmed cervical cancer or CIN3, was analyzed for hypermethylation of the human genes <jats:italic>FAM19A4<\/jats:italic> and <jats:italic>miR124\u20102<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Methylation was detected in 45% (33\/73) of normal LBC samples from women who later developed CIN3+, compared with 10% (3\/31) of normal LBC samples from women without subsequent dysplasia (<jats:italic>P<\/jats:italic>\u2009=\u20090.0006). Overall, methylation was detected in 39% (14\/36), 51% (19\/37), 61% (14\/23) and 70% (7\/10) of LBC samples from women who later developed CIN3, adenocarcinoma in\u00a0situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), respectively. Positive methylation analysis was not significantly more frequent than abnormal cytology of atypical squamous cells of unclear significance or worse (ASCUS+) in LBC samples collected 4\u2009months to 8\u2009years before SCC or AIS; however, prior to the development of ADC, methylation was observed in 7\/10 LBC samples, despite normal cytology. Overall, LBC samples collected before invasive cancer (ADC and SCC) were more frequently positive in the methylation analysis than in cytological analysis of ASCUS+ (<jats:italic>P<\/jats:italic>\u2009=\u20090.048). For LBC samples collected more than 2\u2009years before the development of AIS, SCC or ADC, methylation analysis showed a higher positivity rate than cytology did.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Testing for methylation of <jats:italic>FAM19A4\/miR124\u20102<\/jats:italic> as a triage for HPV\u2010positive women would be useful to identify women at risk of cancer development, especially adenocarcinoma. Further studies are needed to estimate the cost\u2010effectiveness before introducing methylation testing in the screening program.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aogs.14707","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T20:26:30Z","timestamp":1700079990000},"page":"378-386","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cervix cytology samples revealed increased methylation of the human markers <i><scp>FAM19A4<\/scp>\/<\/i><scp><i>miR124<\/i>\u2010<i>2<\/i><\/scp> up to 8\u2009years before adenocarcinoma"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3081-813X","authenticated-orcid":false,"given":"Ylva","family":"Lindroth","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Lund University  Lund Sweden"},{"name":"Clinical Microbiology, Infection Prevention and Control, Office for Medical Services  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