{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T01:04:21Z","timestamp":1794531861676,"version":"4.9.1"},"reference-count":31,"publisher":"BMJ","issue":"7","funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2019,6,14]]},"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The clinical course of high-grade cervical intraepithelial neoplasia (CIN2\/3) is characterised by a high spontaneous regression rate. Histological assessment is unable to differentiate between CIN2\/3 lesions likely to regress and those likely to persist or progress. Most CIN2\/3 lesions are treated by surgical excision, leading to overtreatment of a substantial proportion. In this prospective study, we evaluate the value of DNA methylation of host cell genes, which has shown to be particularly sensitive for the detection of advanced CIN2\/3 and cervical cancer, in the prediction of regression or non-regression of CIN2\/3 lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      This is a multicentre observational longitudinal study with 24-month follow-up. Women referred for colposcopy with an abnormal cervical scrape, who have been diagnosed with CIN2\/3 and a small cervical lesion (\u226450% of cervix) will be asked to participate. Participants will be monitored by 6-monthly cytological and colposcopic examination. In case of clinical progression, participants will receive treatment and exit the study protocol. At baseline and during follow-up, self-sampled cervicovaginal brushes and cervical scrapes will be collected for high-risk human papillomavirus (HPV) testing and\n                      <jats:italic>FAM19A4\/miR124-2<\/jats:italic>\n                      methylation analysis. A colposcopy-directed biopsy will be taken from all participants at the last follow-up visit. The primary study endpoint is regression or non-regression at the end of the study based on the histological diagnosis. Regression is defined as CIN1 or less. Non-regression is defined as CIN2 or worse. The secondary study endpoint is defined as HPV clearance (double-negative HPV test at two consecutive time-points). The association between methylation status and regression probability will be evaluated by means of \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      testing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethics approval was obtained in all participating clinics. Results of the main study will be submitted for publication in a peer-reviewed journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NTR6069; Pre-results<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-029017","type":"journal-article","created":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T12:29:44Z","timestamp":1562675384000},"page":"e029017","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Role of\n                    <i>FAM19A4<\/i>\n                    \/\n                    <i>miR124-2<\/i>\n                    methylation analysis in predicting regression or non-regression of CIN2\/3 lesions: a protocol of an observational longitudinal cohort study"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6903-1505","authenticated-orcid":false,"given":"Wieke W","family":"Kremer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Berkhof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike CG","family":"Bleeker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00eblle AM","family":"Heideman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nienke E","family":"van Trommel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marchien W","family":"van Baal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold 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