{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:08:08Z","timestamp":1791932888156,"version":"4.3.4"},"reference-count":38,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"26","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2022,9,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Cervical screening can prevent cancer by detection and treatment of cervical intraepithelial neoplasia grade 2 or 3 (CIN2\/3). Screening also results in considerable overtreatment because many CIN2\/3 lesions show spontaneous regression when left untreated. In this multicenter longitudinal cohort study of women with untreated CIN2\/3, the prognostic value of FAM19A4\/miR124-2 methylation was evaluated for clinical regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>Women with CIN2\/3 were prospectively followed for 24 months. Surgical excision was replaced by a wait-and-see policy. FAM19A4\/miR124-2 methylation was evaluated on all clinician-collected samples and self-collected samples collected at baseline. Every 6 months, human papillomavirus (HPV) testing and cytology were conducted on a clinician-collected sample, and a colposcopic examination was performed by a gynecologist to exclude progression. At the final study visit, two biopsies were taken. Clinical regression was defined as histologically confirmed absence of CIN2+ or an HPV-negative clinician-collected sample with normal cytology. Regression incidences were estimated using the Kaplan-Meier method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>One hundred fourteen women (median age, 30 years; range, 20-53 years) were included, 80 of whom were diagnosed with CIN2 and 34 with CIN3. During the study, 65.8% of women (75\/114) did not receive surgical treatment. Women with a negative FAM19A4\/miR124-2 result on the baseline clinician-collected sample showed more clinical regression (74.7%) than women with a positive methylation result (51.4%, P = .013). Regression in women with a negative FAM19A4\/miR124-2 methylation test was highest when cytology was atypical squamous cells of undetermined significance\/low-grade squamous intraepithelial lesion (88.4%) or HPV16 was negative (85.1%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Most women with untreated CIN2\/3 and a negative baseline FAM19A4\/miR124-2 methylation test showed clinical regression. Methylation, in combination with cytology or HPV genotyping, can be used to support a wait-and-see policy in women with CIN2\/3.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.21.02433","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T15:59:22Z","timestamp":1651766362000},"page":"3037-3046","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":81,"title":["Clinical Regression of High-Grade Cervical Intraepithelial Neoplasia Is Associated With Absence of\n                    <i>FAM19A4\/miR124-2<\/i>\n                    DNA Methylation (CONCERVE Study)"],"prefix":"10.1200","volume":"40","author":[{"given":"Wieke W.","family":"Kremer","sequence":"first","affiliation":[{"name":"Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5548-4557","authenticated-orcid":false,"given":"St\u00e8fanie","family":"Dick","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6463-7391","authenticated-orcid":false,"given":"Dani\u00eblle A.M.","family":"Heideman","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2327-9839","authenticated-orcid":false,"given":"Renske D.M.","family":"Steenbergen","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike C.G.","family":"Bleeker","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0107-1148","authenticated-orcid":false,"given":"Harold R.","family":"Verhoeve","sequence":"additional","affiliation":[{"name":"OLVG, Obstetrics and Gynaecology, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7245-1714","authenticated-orcid":false,"given":"W. Marchien","family":"van Baal","sequence":"additional","affiliation":[{"name":"Flevoziekenhuis, Obstetrics and Gynaecology, Almere, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3656-947X","authenticated-orcid":false,"given":"Nienke","family":"van Trommel","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Location Antoni van Leeuwenhoek, Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma G.","family":"Kenter","sequence":"additional","affiliation":[{"name":"Center of Gynaecologic Oncology Amsterdam, Location Amsterdam UMC, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2758-9463","authenticated-orcid":false,"given":"Chris J.L.M.","family":"Meijer","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2094-2380","authenticated-orcid":false,"given":"Johannes","family":"Berkhof","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Vrije Universiteit Amsterdam, Epidemiology and Data Science, Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-0920-9"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i3633"},{"key":"b4","first-page":"CD009836","volume":"1","author":"Kyrgiou M","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2011.03252.x"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003665"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003641"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70103-7"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k499"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.2015.1012068"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2008.10.012"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.10.053"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.16395"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-018-5125-8"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3728"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-12-551"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32614"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-14-0237"},{"key":"b19","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33320"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31539"},{"key":"b21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2019.06.002"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-029017"},{"key":"b23","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2003.011841"},{"key":"b24","volume-title":"Richtlijn CIN, AIS en VAIN","author":"Kennisinstituut van de Federatie van Medisch Specialisten","year":"2015"},{"key":"b25","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2019-000343"},{"key":"b26","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3181fe777f"},{"key":"b27","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2010.083626"},{"key":"b28","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2599"},{"key":"b29","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70230-8"},{"key":"b30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2016.02.012"},{"key":"b31","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29824"},{"key":"b32","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.200"},{"key":"b33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.03.018"},{"key":"b34","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz677"},{"key":"b35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.08.026"},{"key":"b36","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-019-1460-0"},{"key":"b38","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01614-4"},{"key":"b39","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.11.1500"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.21.02433","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T18:00:02Z","timestamp":1662573602000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.21.02433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,10]]},"references-count":38,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2022,9,10]]}},"alternative-id":["10.1200\/JCO.21.02433"],"URL":"https:\/\/doi.org\/10.1200\/jco.21.02433","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,10]]},"assertion":[{"value":"2021-10-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-07","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}