{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T01:19:46Z","timestamp":1794532786309,"version":"4.9.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T00:00:00Z","timestamp":1636156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T00:00:00Z","timestamp":1636156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Br J Cancer"],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The introduction of primary HPV screening has doubled the number of colposcopy referrals because of the direct referral of HPV-positive women with a borderline or mild dyskaryosis (BMD) cytology (ASC-US\/LSIL) triage test. Further risk-stratification is warranted to improve the efficiency of HPV-based screening.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study evaluated the discriminative power of <jats:italic>FAM19A4\/miR124-2<\/jats:italic> methylation, HPV16\/18 genotyping and HPV16\/18\/31\/33\/45 genotyping in HPV-positive women with BMD (<jats:italic>n<\/jats:italic>\u2009=\u2009294) in two Dutch screening\u00a0trials. Absolute CIN3+ risks and colposcopy referrals within one screening round were calculated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Methylation analysis discriminated well, yielding a CIN3+ risk of 33.1% after a positive result and a CIN3+ risk of 9.8% after a negative result. HPV16\/18 and HPV16\/18\/31\/33\/45 genotyping resulted in a 27.6% and 24.6% CIN3+ risk after a positive result, and a 13.2% and 9.1% CIN3+ risk after a negative result. Colposcopy referral percentages were 41.2%, 43.2%, and 66.3% for <jats:italic>FAM19A4\/miR124-2<\/jats:italic> methylation, HPV16\/18 and HPV16\/18\/31\/33\/45 genotyping, respectively. The CIN3+ risk after a negative result could be lowered to 2.8% by combining methylation and extended genotyping, at the expense of a higher referral percentage of 75.5%.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The use of <jats:italic>FAM19A4\/miR124-2<\/jats:italic> methylation and\/or HPV genotyping in HPV-positive women with BMD can lead to a substantial reduction in the number of direct colposcopy referrals.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41416-021-01614-4","type":"journal-article","created":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T17:02:48Z","timestamp":1636218168000},"page":"259-264","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Risk-stratification of HPV-positive women with low-grade cytology by FAM19A4\/miR124-2 methylation and HPV genotyping"],"prefix":"10.1038","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5548-4557","authenticated-orcid":false,"given":"St\u00e8fanie","family":"Dick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-9167","authenticated-orcid":false,"given":"Frederique J.","family":"Vink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6463-7391","authenticated-orcid":false,"given":"Dani\u00eblle A. 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The POBASCAM trial was approved by the Medical Ethics Committee of the VU University Medical Center (no 96\/103A) and by the Ministry of Public Health (VWS no 328 650) and registered in the trial register (NTR218; ISRCTN20781131). All participants provided written informed consent. The work in this study was performed in accordance with the Declaration of Helsinki.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"CJLMM and DAMH are minority stockholders of Self-screen BV, a spin-off company of VUmc, which develops, manufactures and licences the high-risk HPV assay and methylation marker assays for cervical cancer screening and holds patents on these tests. CJLMM is part-time director of Self-screen BV. He has been on the speakers bureau and served occasionally on the scientific advisory board (expert meeting) of GSK, QIAGEN, SPMSD\/Merck. He has been co-investigator on a SPMSD sponsored trial, of which his institute received research funding. CJLMM has a very small number of shares of MDxHealth and previously had shares of QIAGEN. DAMH has been on the speaker\u2019s bureau of QIAGEN and serves occasionally on the scientific advisory boards of Pfizer and Bristol-Myers Squibb. SD, FJV, BLW and JB have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}