{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:12:28Z","timestamp":1780917148889,"version":"3.54.1"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["50-53125-98-034"],"award-info":[{"award-number":["50-53125-98-034"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["847845"],"award-info":[{"award-number":["847845"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Human papillomavirus (HPV)-based screening programs still use one-size-fits-all protocols but efficiency and efficacy of programs may be improved by stratifying women based on previous screening results.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>We studied the association between cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and previous screening results in the Population-Based Screening Study Amsterdam (POBASCAM) trial, performed in the Netherlands in the setting of regular screening, where women aged from 29 to 61 years old were invited to cytology and HPV co-testing at enrolment in year 1999\/2002 and at the next round in 2003\/2007. We selected 18,448 women (9,293 from the intervention group and 9,155 from the control group) who tested HPV\u2013negative in 2003\/2007 and did not have cervical intraepithelial neoplasia grade 2 or worse (CIN2+) or hysterectomy after enrolment. Follow-up was collected until 14 years after the 2003\/2007 screen, covering 4 rounds of screening. Risk of CIN3+ and CIN2+ among women with an HPV\u2013negative test, irrespective of previous round results and stratified according to previous round HPV and cytology results, were calculated by the Kaplan\u2013Meier method.<\/jats:p>\n<jats:p>During 14 years of follow-up, 62 CIN3+ cases (24 in the intervention group and 38 in the control group) were detected. HPV\u2013negative women had a 14-year CIN3+ risk of 0.48% (95% confidence interval 0.37 to 0.62) and CIN2+ risk of 1.17% (0.99 to 1.38). The CIN3+ risk among HPV\u2013negative women was increased in women with a previous positive HPV test (2.36%, 1.20 to 4.63; <jats:italic>p<\/jats:italic> &lt; 0.001) or co-test (1.68%, 0.87 to 3.20; <jats:italic>p<\/jats:italic> &lt; 0.001) and, equivalently, decreased in women with a previous negative HPV test (0.43%, 0.33 to 0.57) or a negative co-test (0.43%, 0.33 to 0.57). The CIN3+ risk was not influenced by the previous cytology result. The CIN3+ risk among HPV\u2013negative women was increased after both a previous HPV16\u2013positive test (3.90%, 1.47 to 10.12; <jats:italic>p<\/jats:italic> &lt; 0.001) and a previous HPV16\u2013negative\/HPVother\u2013positive test (1.91%, 0.76 to 4.74; <jats:italic>p<\/jats:italic> = 0.002). For endpoint CIN2+ (147 cases), findings were similar except that the CIN2+ risk was increased after previous abnormal cytology (4.06%, 2.30 to 7.12; <jats:italic>p<\/jats:italic> &lt; 0.001). The presented risk estimates were calculated by tracking histological results through the Dutch nationwide pathology archive (PALGA) and were not adjusted for non-compliance with the colposcopy referral advice.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>HPV\u2013negative women had an increased long-term risk of CIN3+ when the HPV test in the previous screening round was positive. This supports the implementation of risk-based intervals that depend on HPV results in the current and previous screening round.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p>POBASCAM trial, trial registration number <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/ISRCTN20781131\">ISRCTN20781131<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004115","type":"journal-article","created":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T17:22:52Z","timestamp":1666977772000},"page":"e1004115","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Risk of cervical precancer among HPV\u2013negative women in the Netherlands and its association with previous HPV and cytology results: A follow-up analysis of a randomized screening study"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3661-0842","authenticated-orcid":true,"given":"Federica","family":"Inturrisi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8361-9500","authenticated-orcid":true,"given":"Lawrence","family":"Rozendaal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5561-8658","authenticated-orcid":true,"given":"Nienke J.","family":"Veldhuijzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6463-7391","authenticated-orcid":true,"given":"Dani\u00eblle A. M.","family":"Heideman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J. L. M.","family":"Meijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Berkhof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"issue":"1","key":"pmed.1004115.ref001","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S1470-2045(11)70296-0","article-title":"Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial","volume":"13","author":"DC Rijkaart","year":"2012","journal-title":"Lancet Oncol"},{"issue":"Suppl 5","key":"pmed.1004115.ref002","doi-asserted-by":"crossref","first-page":"F88","DOI":"10.1016\/j.vaccine.2012.06.095","article-title":"Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer","volume":"30","author":"M Arbyn","year":"2012","journal-title":"Vaccine"},{"issue":"9916","key":"pmed.1004115.ref003","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S0140-6736(13)62218-7","article-title":"Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials","volume":"383","author":"G Ronco","year":"2014","journal-title":"Lancet"},{"issue":"3 Suppl 1","key":"pmed.1004115.ref004","first-page":"77","article-title":"A first survey of HPV-based screening in routine cervical cancer screening in Italy","volume":"39","author":"G Ronco","year":"2015","journal-title":"Epidemiologia e prevenzione"},{"issue":"2","key":"pmed.1004115.ref005","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ygyno.2014.12.022","article-title":"Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance","volume":"136","author":"WK Huh","year":"2015","journal-title":"Gynecol Oncol"},{"issue":"1","key":"pmed.1004115.ref006","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/s12916-019-1460-0","article-title":"Introduction of primary screening using high-risk HPV DNA detection in the Dutch cervical cancer screening programme: a population-based cohort study","volume":"17","author":"CA Aitken","year":"2019","journal-title":"BMC Med"},{"issue":"3","key":"pmed.1004115.ref007","doi-asserted-by":"crossref","first-page":"113","DOI":"10.5694\/mja2.50223","article-title":"Routine cervical screening by primary HPV testing: early findings in the renewed National Cervical Screening Program","volume":"211","author":"DA Machalek","year":"2019","journal-title":"Med J Aust"},{"key":"pmed.1004115.ref008","unstructured":"RIVM. 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