{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:37:23Z","timestamp":1792255043239,"version":"4.4.0"},"reference-count":43,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"content-version":"unspecified","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,10,9]]},"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aim to assess the efficacy and safety of therapeutic human papillomavirus (HPV) vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN 2\/3).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources<\/jats:title>\n                    <jats:p>PubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up to 31 January 2022.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Eligibility criteria<\/jats:title>\n                    <jats:p>Phase II\/III randomised controlled trials (RCTs) and single-arm studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN 2\/3 lesions were included. Studies evaluating only safety and side effects of the vaccine were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data extraction and synthesis<\/jats:title>\n                    <jats:p>Two independent reviewers extracted data and evaluated study quality. A random-effect model was used to pool the proportions of regression and\/or HPV clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>12 trials met the inclusion criteria. Out of 734\u2009women (all studies considered) receiving therapeutic HPV vaccine for CIN 2\/3, 414 regressed to normal\/CIN 1 with an overall proportion of regression of 0.54 (95% CI 0.39 to 0.69) for vaccinated group; 166\u2009women (from five RCTs) receiving placebo only achieving a pooled normal\/CIN 1 regression of 0.27 (95% CI 0.20 to 0.34). When including only the five two-arm studies, the regression proportion for the 410 vaccine group participants was higher than that of the 166 control group participants (relative risk (RR) 1.52; 95%\u2009CI 1.14 to 2.04). The pooled proportion of high-risk human papillomavirus (hrHPV) clearance was 0.42 (95% CI 0.32 to 0.52) in the vaccine group (six studies with a total of 357 participants) and 0.17 (95% CI 0.11 to 0.26) in the control group (three RCTs with a total of 104 participants). Based on these three RCTs, the hrHPV clearance was significantly higher in the vaccinated group (250 participants) compared with the control group (RR 2.03; 95%\u2009CI 1.30 to 3.16). Similar results were found regarding HPV 16\/18 clearance. No significant unsolicited adverse events have been consistently reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The efficacy of the therapeutic vaccines in the treatment of CIN 2\/3 was modest. Implementation issues such as feasibility, acceptability, adoption and cost-effectiveness need to be further studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD42022307418.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2022-069616","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T23:20:17Z","timestamp":1698189617000},"page":"e069616","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Efficacy and safety of therapeutic HPV vaccines to treat CIN 2\/CIN 3 lesions: a systematic review and meta-analysis of phase II\/III clinical trials"],"prefix":"10.1136","volume":"13","author":[{"given":"Ahmadaye","family":"Ibrahim Khalil","sequence":"first","affiliation":[{"name":"International Agency for Research on Cancer, Lyon, Rh\u00f4ne-Alpes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, Lyon, Rh\u00f4ne-Alpes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Muwonge","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, Lyon, Rh\u00f4ne-Alpes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Sauvaget","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, Lyon, Rh\u00f4ne-Alpes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0124-4050","authenticated-orcid":false,"given":"Partha","family":"Basu","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, Lyon, Rh\u00f4ne-Alpes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"2025121406541130000_13.10.e069616.1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1177\/2150131917742299","article-title":"The uptake of human Papillomavirus vaccination and its associated factors among adolescents: A systematic review","volume":"8","author":"Loke","year":"2017","journal-title":"J Prim Care Community Health"},{"key":"2025121406541130000_13.10.e069616.2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57149"},{"key":"2025121406541130000_13.10.e069616.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2017.08.006"},{"key":"2025121406541130000_13.10.e069616.4","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27485"},{"key":"2025121406541130000_13.10.e069616.5","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.bpobgyn.2011.04.007","article-title":"Management options for Cervical intraepithelial Neoplasia","volume":"25","author":"Petry","year":"2011","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"2025121406541130000_13.10.e069616.6","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/1471-0528.17251","article-title":"Efficacy, acceptability and safety of Ablative versus Excisional procedure in the treatment of histologically confirmed CIN2\/3: a systematic review BJOG","volume":"130","author":"Zhang","year":"2023","journal-title":"BJOG"},{"key":"2025121406541130000_13.10.e069616.7","unstructured":"World Health Organization . 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