{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:22:33Z","timestamp":1792106553340,"version":"4.4.0"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University College Hospitals NHS Foundation Trust"},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C8162\/A16892"],"award-info":[{"award-number":["C8162\/A16892"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C8162\/A27047"],"award-info":[{"award-number":["C8162\/A27047"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","award":["C8162\/A25356"],"award-info":[{"award-number":["C8162\/A25356"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["2021-00289 & 2023-01809"],"award-info":[{"award-number":["2021-00289 & 2023-01809"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Swedish Research Council for Health, Working Life","award":["2023-01221"],"award-info":[{"award-number":["2023-01221"]}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Health Service","award":["41934"],"award-info":[{"award-number":["41934"]}]}],"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) testing of self-collected vaginal samples has potential to improve coverage of cervical screening programmes, but current guidelines mostly require those HPV positive on a self-sample to attend for routine screening.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>A pragmatic modified stepped-wedge implementation feasibility trial was conducted at primary care practices in England. Individuals aged 25 to 64 years who were at least 6 months overdue for cervical screening could provide a self-collected sample. The primary outcomes included the monthly proportion of non-attenders screened, changes in coverage, and uptake within 90 days. Self-samples from 7,739 individuals were analysed using Roche Cobas 4800. Individuals with a positive self-sample were encouraged to attend clinical screening.<\/jats:p>\n<jats:p>In this post hoc study of the trial, we related the HPV type (HPV16, HPV18, or other high-risk type) and cycle threshold (Ct) value on the self-sample to the results of clinician-collected sample and cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We wished to triage HPV\u2013positive individuals to immediate colposcopy, clinician sampling, or 12-month recall depending on risk. A total of 1,001 women tested positive through self-samples, and 855 women who had both an HPV\u2013positive self-sample and a subsequent clinician-sample were included in this study. Of these, 71 (8.3%) had CIN2+. Self-sample Ct values were highly predictive of HPV in the clinician sample. Combining HPV type and Ct value allowed stratification into 3 risk groups; 44\/855 (5%) were high-risk of whom 43% (19\/44, 95% confidence interval [29.7%, 57.8%]) had CIN2+. The majority (52.9%, 452\/855) were low-risk, of whom 4% (18\/452, 95% CI [2.5%, 6.2%]) had CIN2+. The main limitation of our study was the colposcopy assessment was restricted to individuals who had abnormal cytology after positive results of both self-sample and clinician-collected sample.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>HPV type and Ct value on HPV\u2013positive self-samples may be used for triage. The difference in the risk of CIN2+ in these groups appears sufficient to justify differential clinical management. A prospective study employing such triage to evaluate laboratory workflow, acceptability, and follow-up procedure and to optimise clinical performance seems warranted.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Trial Registration<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.hra.nhs.uk\/planning-and-improving-research\/application-summaries\/research-summaries\/youscreen-v10\/\" xlink:type=\"simple\">ISRCTN12759467<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004494","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T18:49:17Z","timestamp":1734029357000},"page":"e1004494","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Human papillomavirus genotype and cycle threshold value from self-samples and risk of high-grade cervical lesions: A post hoc analysis of a modified stepped-wedge implementation feasibility trial"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4718-1414","authenticated-orcid":true,"given":"Jiayao","family":"Lei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2604-3928","authenticated-orcid":true,"given":"Kate","family":"Cuschieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasit","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Lawrence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Deats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"YouScreen trial team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1509-8744","authenticated-orcid":true,"given":"Peter","family":"Sasieni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4407-7451","authenticated-orcid":true,"given":"Anita W. W.","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"key":"pmed.1004494.ref001","journal-title":"Global strategy to accelerate the elimination of cervical cancer as a public health problem"},{"key":"pmed.1004494.ref002","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"},{"key":"pmed.1004494.ref003","article-title":"Primary cervical screening with high risk human papillomavirus testing: observational study","volume":"l240","author":"M Rebolj","year":"2019","journal-title":"BMJ"},{"key":"pmed.1004494.ref004","doi-asserted-by":"crossref","first-page":"e068776","DOI":"10.1136\/bmj-2021-068776","article-title":"Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data","author":"M Rebolj","year":"2022","journal-title":"BMJ"},{"key":"pmed.1004494.ref005","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1056\/NEJMsr2030640","article-title":"The IARC Perspective on Cervical Cancer Screening","volume":"385","author":"V Bouvard","year":"2021","journal-title":"N Engl J Med"},{"key":"pmed.1004494.ref006","first-page":"100593","article-title":"Performance of cervical cytology and HPV testing for primary cervical cancer screening in Latin America: an analysis within the ESTAMPA study","volume":"26","author":"AT Ram\u00edrez","year":"2023","journal-title":"Lancet Reg Health Am"},{"key":"pmed.1004494.ref007","doi-asserted-by":"crossref","first-page":"k4823","DOI":"10.1136\/bmj.k4823","article-title":"Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses","volume":"363","author":"M Arbyn","year":"2018","journal-title":"BMJ"},{"key":"pmed.1004494.ref008","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1158\/1055-9965.EPI-22-0712","article-title":"Sociodemographic Characteristics and Screening Outcomes of Women Preferring Self-Sampling in the Dutch Cervical Cancer Screening Programme: A Population-Based Study","volume":"32","author":"CA Aitken","year":"2023","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"pmed.1004494.ref009","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1002\/ijc.32374","article-title":"Increasing participation in cervical screening by targeting long-term nonattenders: Randomized health services study","volume":"145","author":"KM Elfstr\u00f6m","year":"2019","journal-title":"Int J Cancer"},{"key":"pmed.1004494.ref010","doi-asserted-by":"crossref","unstructured":"Lim A, Deats K, Gambell J, Lawrence A, Lei J, Lyons M, et al. Opportunistic Offering of Self-Sampling to Non-Attenders within the English Cervical Screening Programme: A Pragmatic, Multicentre, Implementation Feasibility Trial with Randomly Allocated Cluster Intervention Start Dates (Youscreen). 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Rebolj","year":"2016","journal-title":"PLoS ONE."},{"key":"pmed.1004494.ref031","doi-asserted-by":"crossref","first-page":"e035796","DOI":"10.1136\/bmjopen-2019-035796","article-title":"Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol","volume":"10","author":"M Almonte","year":"2020","journal-title":"BMJ Open"},{"key":"pmed.1004494.ref032","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1097\/AOG.0000000000000669","article-title":"Use of Primary High-Risk Human Papillomavirus Testing for Cervical Cancer Screening: Interim Clinical Guidance.","volume":"125","author":"WK Huh","year":"2015","journal-title":"Obstet Gynecol"},{"key":"pmed.1004494.ref033","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1016\/S0140-6736(21)02178-4","article-title":"The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 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