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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

Objectives: We aims to assess the efficacy and safety of therapeutic HPV vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN2/3). Design: This study is a systematic review and meta-regression that follows 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 January 31, 2022. Eligibility criteria: Phase II/III studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN2/3 lesions were included. Data extraction and synthesis: Two independent reviewers extracted data, 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 the total 734 women receiving therapeutic HPV vaccine for CIN 2/3, 414 regressed to normal/CIN1 with the overall proportion of regression of 0.54 (95%CI: 0.39, 0.69) for vaccinated group. Correspondingly, 166 women receiving placebo only achieving the pooled normal/CIN1 regression of 0.27 (95%CI: 0.20, 0.34). When only including two-arm studies, the regression proportion of the vaccine group was higher than that of control group (relative risk (RR): 1.52, 95%CI: 1.14, 2.04). Six studies reported the efficacy of the therapeutic vaccines to clear high-risk human papillomavirus (hrHPV) with the pooled proportion of hrHPV clearance of 0.42 (95%CI: 0.32, 0.52) for the vaccine group and 0.17 (95%CI: 0.11, 0.26) for the control group and the RR of 2.03 (95%CI: 1.30, 3.16). Similar results were found regarding HPV16/18 clearance. No significant unsolicited adverse events have been consistently reported. Conclusions: The efficacy of the therapeutic vaccines in the treatment of CIN2/3 was modest. Besides, the implementation issues like feasibility, acceptability, adoption, and cost-effectiveness need to be further studied. PROSPERO registration number: CRD42020189617