Effectiveness and Safety of Therapeutic Vaccines for Precancerous Cervical Lesions: A Systematic Review and Meta-Analysis

Cai, Shan; Tan, Xiaoyu; Miao, Ke; Li, Dantong; Cheng, Shijie; Li, Pei; Zeng, Xueyang; Sun, Feng

doi:10.3389/fonc.2022.918331

Cited by 3 publications

(6 citation statements)

References 58 publications

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“…This permitted us to provide a robust estimate of the efficacy of therapeutic vaccines against the most important endpoint of regression of high-grade lesions. A recently published systematic review of therapeutic vaccines showed that the overall incidence rate of CIN 2/3 regression induced by the vaccines (52.08%; 95% CI 42.08% to 62.01%) was comparable to our study 43…”

Section: Discussionsupporting

confidence: 89%

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

Ibrahim Khalil,

Zhang,

Muwonge

et al. 2023

BMJ Open

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ObjectivesWe 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).DesignSystematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.Data sourcesPubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up to 31 January 2022.Eligibility criteriaPhase 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 synthesisTwo independent reviewers extracted data and evaluated study quality. A random-effect model was used to pool the proportions of regression and/or HPV clearance.Results12 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.ConclusionsThe 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 numberCRD42022307418.

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Section: Discussionsupporting

confidence: 89%

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

Ibrahim Khalil,

Zhang,

Muwonge

et al. 2023

BMJ Open

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“…This result is consistent with previous findings of similar meta-analyses conducted in 2020–2022 and involving 9–11 studies with pooled VE outcomes ranging between 46 and 65% regardless of timing of vaccination. 11 12 24–26 It is likely that the nine additional studies in our PAVIVE Study did not affect the overall result showing robustness and benefit of HPV vaccination against CIN2+ recurrence irrespective of the HPV genotype. Moreover, another two meta-analyses evaluating recurrence rates for only vaccine genotypes of HPV16 and 18, confirmed a 63–73% reduction in CIN2+ recurrence rates.…”

Section: Discussionmentioning

confidence: 87%

“…Therefore, we followed up on the recently published metaanalyses and reviews in an attempt to establish, specifically, an association (if any) between timing of vaccination and surgical excision with regard to the outcome. [11][12][13][14]…”

Section: Systematic Reviewmentioning

confidence: 99%

Timing of HPV vaccination as adjuvant treatment of CIN2+ recurrence in women undergoing surgical excision: a meta-analysis and meta-regression

Petráš,

Dvořák,

Lomozová

et al. 2023

Sex Transm Infect

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ObjectiveThe main aim was to determine the overall vaccine effectiveness (VE) against recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+) including specific VE associated with timing of human papillomavirus (HPV) vaccination using data from published studies.DesignMeta-analysis and meta-regression.Data sourcesA computerised literature search was undertaken using the MEDLINE, EMBASE, International Pharmaceutical Abstracts, Derwent Drug File, ProQuest Science and Technology, Cochrane and MedRxiv databases. To be eligible, the studies, with no language restrictions, had to be published between 1 January 2001 and 25 May 2023.Review methodsIncluded were studies with an unvaccinated reference group that assessed CIN2+ recurrence irrespective of the HPV genotype in women undergoing conisation provided. The present study was carried out in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology guidelines. The risk of study bias was assessed using the Newcastle–Ottawa Quality Assessment Scale. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to assess the strength of evidence for the primary outcome. Data synthesis was conducted using meta-analysis and meta-regression.ResultsOut of a total of 14 322 publications, 20 studies with a total of 21 estimates were included. The overall VE against recurrent CIN2+ irrespective of the HPV genotype achieved 69.5% (95% CI: 54.7% to 79.5%). While the HPV vaccine valency, follow-up duration, type of study including its risk of bias had no effect on VE, the highest VE of 78.1% (95% CI: 68.7% to 84.7%) was reported for women receiving their first dose not earlier than the day of excision. This outcome was supported by additional analyses and a VE prediction interval ranging from 67.1% to 85.4%.ConclusionsThe outcome of this meta-analysis and meta-regression convincingly showed the beneficial effect of post-excisional HPV vaccination against CIN2+ recurrence. Studies published to date have been unable to determine whether or not vaccination, completed or initiated before conisation, would be associated with more favourable results.PROSPERO registration numberCRD42022353530.

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“…However, this estimate may be overestimated by including in their analysis both prophylactic and therapeutic vaccines, as the two vaccines have entirely different modes of action. 39 To conclude, the modest efficacy of the therapeutic vaccines in the treatment of high-grade cervical cancer precursors may not justify replacing the highly effective ablative or excisional treatment with these new interventions. The existing vaccines may be made more effective through innovative approaches for treatment such as use of peptide-based vaccines to boost the effect of virus-based vaccines to overcome the anti-vector immunity.…”

Section: Discussionmentioning

confidence: 99%

“…However, this estimate may be overestimated by including in their analysis both prophylactic and therapeutic vaccines, as the two vaccines have entirely different modes of action. 39…”

Section: Discussionmentioning

confidence: 99%

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

Khalil

Zhang

Muwonge

et al. 2022

Preprint

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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

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Effectiveness and Safety of Therapeutic Vaccines for Precancerous Cervical Lesions: A Systematic Review and Meta-Analysis

Cited by 3 publications

References 58 publications

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

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

Timing of HPV vaccination as adjuvant treatment of CIN2+ recurrence in women undergoing surgical excision: a meta-analysis and meta-regression

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

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