{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T15:13:44Z","timestamp":1778944424323,"version":"3.51.4"},"reference-count":36,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"QIAGEN N.V."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Detecting hypermethylation of tumour suppressor genes could provide an alternative to liquid-based cytology (LBC) triage within HPV primary cervical screening. The impact of using the QIAsure\u00ae FAM19A4\/mir124-2 DNA Methylation Test (QIAGEN, N.V, Hilden, Germany) on CIN3+ diagnoses, retention, unnecessary colposcopies, and programme costs is unknown. A decision-tree model was developed to compare LBC with the QIAsure Methylation testing to guide colposcopy referral. Incorporating clinician- and self-sampling pathways the model was informed by the Dutch cervical cancer screening programme, published studies, and manufacturer data. Clinical and cost outcomes were assessed using two scenarios for DNA methylation testing and LBC relative performance. Sensitivity analyses (deterministic and probabilistic) were performed to assess model and parameter uncertainty. A range of self-sampling uptake was assessed in scenario analyses. For the screening cohort (n = 807,269) where 22.1% self-sampled, the number of unnecessary colposcopies and CIN3+ diagnoses varied according to the relative performance of methylation testing and LBC. Irrespective of relative performance, the cost per complete screen was lower and fewer people were lost to follow-up when using DNA methylation testing. The results indicate that, within an HPV primary screening programme that incorporates self-sampling, using the QIAsure Methylation Test for triage reduces the cost per screen compared to LBC.<\/jats:p>","DOI":"10.3390\/diagnostics13243612","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T06:01:07Z","timestamp":1701842467000},"page":"3612","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Comparing the Costs and Diagnostic Outcomes of Replacing Cytology with the QIAsure DNA Methylation Test as a Triage within HPV Primary Cervical Cancer Screening in The Netherlands"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-0333","authenticated-orcid":false,"given":"Krishnan","family":"Puri Sudhir","sequence":"first","affiliation":[{"name":"Aquarius Population Health, Unit 29 Tileyard Studios, London N7 9AH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Kagenaar","sequence":"additional","affiliation":[{"name":"Aquarius Population Health, Unit 29 Tileyard Studios, London N7 9AH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Meijer","sequence":"additional","affiliation":[{"name":"Self-Screen B.V., Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albertus T.","family":"Hesselink","sequence":"additional","affiliation":[{"name":"Self-Screen B.V., Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4222-9394","authenticated-orcid":false,"given":"Elisabeth","family":"Adams","sequence":"additional","affiliation":[{"name":"Aquarius Population Health, Unit 29 Tileyard Studios, London N7 9AH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katy M. E.","family":"Turner","sequence":"additional","affiliation":[{"name":"Aquarius Population Health, Unit 29 Tileyard Studios, London N7 9AH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susie","family":"Huntington","sequence":"additional","affiliation":[{"name":"Aquarius Population Health, Unit 29 Tileyard Studios, London N7 9AH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0140-6736(13)60022-7","article-title":"Human papillomavirus and cervical cancer","volume":"382","author":"Crosbie","year":"2013","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chrysostomou, C.A., Stylianou, C.D., Constantinidou, A., and Kostrikis, G.L. (2018). Cervical Cancer Screening Programs in Europe: The Transition Towards HPV Vaccination and Population-Based HPV Testing. Viruses, 10.","DOI":"10.3390\/v10120729"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1001\/jama.2019.4595","article-title":"Cervical Cancer Screening: More Choices in 2019","volume":"321","author":"Sawaya","year":"2019","journal-title":"JAMA"},{"key":"ref_5","unstructured":"The National Institute for Public Health and Environment (2023, September 11). Framework for the Execution of Cervical Cancer Population Screening. Available online: https:\/\/www.rivm.nl\/documenten\/framework-for-execution-of-cervical-cancer-population-screening."},{"key":"ref_6","unstructured":"(2023, September 11). Actuele Ontwikkelingen\u2014Bevolkingsonderzoek Baarmoederhalskanker. Available online: https:\/\/www.rivm.nl\/bevolkingsonderzoek-baarmoederhalskanker\/professionals\/actuele-ontwikkelingen."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.clon.2021.06.013","article-title":"Eliminating cervical cancer: Progress and challenges for high-income countries","volume":"33","author":"Smith","year":"2021","journal-title":"Clin. Oncol."},{"key":"ref_8","unstructured":"Gezondheidsraad (2022, December 01). Verbetermogelijkheden Bevolkingsonderzoek Baarmoederhalskanker. Den Haag. Available online: https:\/\/www.gezondheidsraad.nl\/documenten\/adviezen\/2021\/10\/19\/verbetermogelijkheden-bevolkingsonderzoek-baarmoederhalskanker."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"810","DOI":"10.7326\/0003-4819-132-10-200005160-00009","article-title":"Accuracy of the Papanicolaou Test in Screening for and Follow-up of Cervical Cytologic Abnormalities: A Systematic Review","volume":"132","author":"Nanda","year":"2000","journal-title":"Ann. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1093\/oxfordjournals.aje.a117485","article-title":"Meta-analysis of Pap Test Accuracy","volume":"141","author":"Fahey","year":"1995","journal-title":"Am. J. Epidemiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.1365-2303.2012.00982.x","article-title":"Prospective parallel randomized trial of the MultiCyteTM ThinPrep\u00ae imaging system: The Scottish experience","volume":"24","author":"Palmer","year":"2013","journal-title":"Cytopathology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Aitken, C.A., Van Agt, H.M.E., Siebers, A.G., Van Kemenade, F.J., Niesters, H.G.M., Melchers, W.J.G., Vedder, J.E.M., Schuurman, R., Van Den Brule, A.J.C., and Van Der Linden, H.C. (2019). Introduction of primary screening using high-risk HPV DNA detection in the Dutch cervical cancer screening programme: A population-based cohort study. BMC Med., 17.","DOI":"10.1186\/s12916-019-1460-0"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"dju423","DOI":"10.1093\/jnci\/dju423","article-title":"Informed Cytology for Triaging HPV-Positive Women: Substudy Nested in the NTCC Randomized Controlled Trial","volume":"107","author":"Bergeron","year":"2015","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1128\/JCM.02440-05","article-title":"High concordance of results of testing for human papillomavirus in cervicovaginal samples collected by two methods, with comparison of a novel self-sampling device to a conventional endocervical brush","volume":"44","author":"Brink","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"106900","DOI":"10.1016\/j.ypmed.2021.106900","article-title":"Worldwide use of HPV self-sampling for cervical cancer screening","volume":"154","author":"Serrano","year":"2022","journal-title":"Prev. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1158\/1055-9965.EPI-14-0347","article-title":"Combined CADM1\/MAL methylation and cytology testing for colposcopy triage of high-risk HPV-positive women","volume":"23","author":"Hesselink","year":"2014","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1002\/ijc.31539","article-title":"Cervical cancer risk in HPV-positive women after a negative FAM19A4\/mir124-2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow-up","volume":"143","author":"Berkhof","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_18","unstructured":"IKNL (2023, October 11). Monitor Bevolkingsonderzoek Baarmoederhalskanker 2021. Available online: https:\/\/www.rivm.nl\/documenten\/monitor-bevolkingsonderzoek-baarmoederhalskanker-2021."},{"key":"ref_19","unstructured":"IKNL (2023, September 11). Monitor Bevolkingsonderzoek Baarmoederhalskanker 2019. Available online: https:\/\/www.rivm.nl\/documenten\/monitor-bevolkingsonderzoek-baarmoederhalskanker-2019."},{"key":"ref_20","unstructured":"(2023, September 11). The Minister of Health, Welfare and Sport, The Netherlands. Subsidieregeling Publieke Gezondheid (Public Health Subsidy Regulations), Available online: https:\/\/wetten.overheid.nl\/BWBR0018743\/2019-01-01\/#HoofdstukII_Paragraaf2_Artikel46."},{"key":"ref_21","unstructured":"Nederlandse Zorg Autoriteit (2023, September 11). Open Data van de Nederlandse Zorgautoriteit, Available online: https:\/\/www.opendisdata.nlt."},{"key":"ref_22","unstructured":"(2022, November 30). IMF Data. Available online: https:\/\/data.imf.org\/regular.aspx?key=61015892."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/ijc.33320","article-title":"Methylation markers FAM19A4 and miR124-2 as triage strategy for primary human papillomavirus screen positive women: A large European multicenter study","volume":"148","author":"Bonde","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1002\/ijc.29824","article-title":"Comparing the performance of FAM19A4 methylation analysis, cytology and HPV16\/18 genotyping for the detection of cervical (pre)cancer in high-risk HPV-positive women of a gynecologic outpatient population (COMETH study)","volume":"138","author":"Luttmer","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.ygyno.2019.06.002","article-title":"Long-term CIN3+ risk of HPV positive women after triage with FAM19A4\/miR124-2 methylation analysis","volume":"154","author":"Dick","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1200\/JCO.21.02433","article-title":"Clinical Regression of High-Grade Cervical Intraepithelial Neoplasia Is Associated with Absence of FAM19A4\/miR124-2 DNA Methylation (CONCERVE Study)","volume":"40","author":"Kremer","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"k499","DOI":"10.1136\/bmj.k499","article-title":"Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: Systematic review and meta-analysis","volume":"360","author":"Tainio","year":"2018","journal-title":"BMJ"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1470-2045(08)70103-7","article-title":"Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: A retrospective cohort study","volume":"9","author":"McCredie","year":"2008","journal-title":"Lancet Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/bjc.2016.200","article-title":"FAM19A4 methylation analysis in self-samples compared with cervical scrapes for detecting cervical (pre)cancer in HPV-positive women","volume":"115","author":"Luttmer","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/2046-4053-2-35","article-title":"Screening for cervical cancer: A systematic review and meta-analysis","volume":"2","author":"Peirson","year":"2013","journal-title":"Syst. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13027-020-00280-0","article-title":"Cervical cancer prevention among long-term screening non-attendees by vaginal self-collected samples for hr-HPV mRNA detection","volume":"15","author":"Ernstson","year":"2020","journal-title":"Infect. Agent. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"c1040","DOI":"10.1136\/bmj.c1040","article-title":"HPV testing on self collected cervicovaginal lavage specimens as screening method for women who do not attend cervical screening: Cohort study","volume":"340","author":"Gok","year":"2010","journal-title":"BMJ"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.cmi.2019.09.006","article-title":"Primary HPV-based cervical cancer screening in Europe: Implementation status, challenges, and future plans","volume":"26","author":"Maver","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41416-021-01614-4","article-title":"Risk-stratification of HPV-positive women with low-grade cytology by FAM19A4\/miR124-2 methylation and HPV genotyping","volume":"126","author":"Dick","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ypmed.2019.04.025","article-title":"Experience with HPV self-sampling and clinician-based sampling in women attending routine cervical screening in the Netherlands","volume":"125","author":"Polman","year":"2019","journal-title":"Prev. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Rebolj, M., Bonde, J., Preisler, S., Ejegod, D., Rygaard, C., and Lynge, E. (2016). Human Papillomavirus assays and cytology in primary cervical screening of women aged 30 years and above. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147326"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/24\/3612\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:34:03Z","timestamp":1760132043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/24\/3612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,6]]},"references-count":36,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["diagnostics13243612"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13243612","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,6]]}}}