{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:16:37Z","timestamp":1786115797850,"version":"build-2736575974"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To enhance global vaccine coverage and reduce costs, Human papillomavirus (HPV) immunization schedules are shifting from the standard three\u2013dose (3D) regimen toward reduced\u2013dose (1D or 2D) schedules. We aimed to evaluate the comparative immunogenicity, efficacy, and safety of diverse dose schedules and vaccine types using a Bayesian network meta\u2013analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two reviewers independently searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, and Wanfang Data from inception to February 15, 2026, for randomized controlled trials (RCTs) evaluating different dose schedules of HPV vaccines in females aged 9\u201326 years. Primary outcomes were HPV\u201316\/18 Seroconversion rates (SCR) and 6\u2013month Persistent infection (PI). A Bayesian random\u2013effects model was constructed using the multinma package in R, and treatments were ranked using the Surface Under the Cumulative Ranking (SUCRA) values.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>For immunogenicity, the 9v\u20133D regimen demonstrated the highest SCR compared with placebo (OR 62.45, 95% CrI 15.20\u2013158.30; SUCRA 0.96). However, these large effect estimates are largely driven by near\u2013zero events in placebo arms. Regarding protective efficacy against PI, while 3\u2013dose regimens ranked highest (9v\u20133D SUCRA 0.95; 2v\u20133D SUCRA 0.89), single\u2013dose schedules (1D) maintained clinically significant protection (e.g., 2v\u20131D vs. placebo: OR 0.32, 95% CrI 0.07\u20130.96; SUCRA 0.61). Safety rankings identified 1D schedules as having the lowest risk of injection\u2013site pain (SUCRA: 2v\u20131D 88.0%, 9v\u20131D 82.0%). Subgroup analysis suggested comparable efficacy of 2\u2013dose regimens in adolescents aged 9\u201314 years compared to the standard 3D regimen (P\u2013interaction = 0.04).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although reduced\u2013dose schedules induce lower antibody titers than the standard 3\u2013dose regimen, they provide robust protective efficacy against persistent HPV infection with a superior safety profile. Our findings support the widespread adoption of 2\u2013dose schedules in adolescents and suggest that a single\u2013dose strategy is a viable alternative in resource\u2013constrained settings to accelerate the elimination of cervical cancer. However, given the surrogate nature of the study endpoints and the limitations of network meta-analysis for establishing non-inferiority, cautious interpretation of these results is warranted, and further long-term clinical endpoint data are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1883217","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T05:32:31Z","timestamp":1785994351000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunogenicity, efficacy, and safety of different dose schedules of human papillomavirus vaccines: a Bayesian network meta\u2013analysis of randomized controlled trials"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Gynecology, Zhejiang Provincial People\u2019s Hospital Bijie Hospital","place":["Guizhou, Bijie, 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Hospital","place":["Guizhou, Bijie, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-feng","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Evidence-based medicine, Heping Hospital Affiliated to Changzhi Medical College","place":["Shanxi, Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-9896(199909)189:1<12::aid-path431>3.0.co;2-f","article-title":"Human papillomavirus is a necessary cause of invasive cervical cancer 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