OBJECTIVES: 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)., DESIGN: Systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations., DATA SOURCES: PubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up to 31 January 2022., ELIGIBILITY CRITERIA: 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., DATA EXTRACTION AND SYNTHESIS: 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., RESULTS: 12 trials met the inclusion criteria. Out of 734 women (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 women (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% CI 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% CI 1.30 to 3.16). Similar results were found regarding HPV 16/18 clearance. No significant unsolicited adverse events have been consistently reported., CONCLUSIONS: 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., PROSPERO REGISTRATION NUMBER: CRD42022307418. Copyright © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
- All age groups
- Human papillomavirus (HPV)
- Efficacy/effectiveness
- Safety
