Efficacy of mRNA-based HPV Vaccines in Inducing Immune Response and Preventing Oncogenic Outcomes: A systematic review and meta-analysis

Abstract

Background Human papillomavirus (HPV) infection represents a substantial global health burden, being the primary etiological agent of cervical cancer, anogenital and oropharyngeal malignancies. Although prophylactic virus-like particle (VLP) vaccines have been successfully implemented, they lack therapeutic efficacy against established infections and lesions in the host. The messenger RNA (mRNA) vaccine platform has emerged as a promising alternative, offering rapid manufacturing and the ability to induce potent cellular immune responses required for effective therapeutic outcomes. Objective This systematic review aimed to synthesize and evaluate preclinical evidence regarding the immunogenicity and protective efficacy of mRNA-based HPV vaccines in animal models, focusing on their ability to prevent oncogenic infections and induce regression of established tumors. Methods The study is registered in Prospero (CRD420261362037, 14 July 2026). A systematic search of PubMed, Scopus, Europe PMC, and ScienceDirect databases was conducted according to the PRISMA 2020 guidelines. Eligible studies included in vivo preclinical experimental research evaluating mRNA vaccines targeting high-risk HPV types (HPV-16 and HPV-18) in animal models. Immunogenicity (CD8+ T-cell responses and IgG titers) and oncogenic outcome (tumor volume and survival rate) data were extracted. The risk of bias was assessed using the SYRCLE’s risk-of-bias tool. The meta-analysis utilized a random-effects model to calculate standardized mean differences (SMD) and evaluate heterogeneity via the I 2 statistic. Result and Conclusion Ten studies met the inclusion criteria and provided detailed data for the analysis. mRNA vaccines have demonstrated high immunogenicity, significantly expanding antigen-specific CD8+ T-cell populations and inducing robust IFN gamma secretion. The pooled results indicated a significant reduction in tumor volume (SMD -2.305; 95% CI: −2.64 to −1.97) and near-complete viral load reduction in the challenge models. High-risk HPV mRNA vaccines delivered via lipid nanoparticles (LNPs) or lipopolyplexes (LPPs) have a promising therapeutic potential as both prophylactic and therapeutic agents, supporting their advancement to clinical trials.