Dados do Trabalho

Título

SAFETY, EFFICACY, AND IMMUNOGENICITY OF THERAPEUTIC VACCINES FOR PATIENTS WITH HIGH-GRADE CERVICAL INTRAEPITHELIAL NEOPLASIA ASSOCIATED WITH HPV: A SYSTEMATIC REVIEW AND META-ANALYSIS

Introdução

Despite the knowledge that HPV is responsible for high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer, little is known about the use of therapeutic vaccines as treatment.

Objetivo

To synthesize and evaluate the evidence from clinical trials on the safety, efficacy, and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade CIN associated with HPV.

Método

A systematic review and meta-analysis of randomized clinical trials (RCTs) and non-randomized clinical trials (NRCTs) was performed following the PRISMA guidelines. We searched MEDLINE/PubMed, Embase, CENTRAL, Web of Science, Scopus, and LILACS, from the database inception to Dec 31, 2020. Primary outcomes related to the safety, efficacy, and immunogenicity of these vaccines were assessed by analyzing the adverse/toxic effects associated with the therapeutic vaccine administration; via histopathological regression of the lesion and/or regression of the lesion size and by viral clearance; and through the immunological response of individuals who received treatment compared to those who did not or before and after receiving the vaccine, respectively. Heterogeneity was assessed by the I2 test. Meta-analyses of the prevalence rate were conducted using random-effects models, following by GRADE. This study is registered with PROSPERO: CRD42017077428.

Resultado

A total of 1,184 studies were identified, and 15 met all criteria. Overall, the therapeutic vaccines were heterogeneous regarding their formulation, dose, intervention protocol and routes of administration. In most studies (n=14), the vaccines were safe and well tolerated, with clinical efficacy observed in 93.3% with respect to lesions and histopathological regression or viral clearance. In addition, 73.3% of the studies showed favorable immunological responses against HPV, and 54.5% showed a positive correlation between immunogenicity and clinical response, indicating promising results that should be further investigated. Most PR meta-analyses showed inconsistent results. The certainty of the evidence of the outcomes was low or very low, as classified using the GRADE approach.

Conclusão

Therapeutic vaccines, although urgently needed, still present barriers to be overcome before dissemination to the population, requiring greater investments in well-designed phase III RCTs to benefit patients with CIN 2/3 by preventing progression to cervical cancer and consequently having a positive impact on patient survival rates and quality of life.

Palavras-chave

Neoplasms. Cervical Intraepithelial Neoplasia HPV. Vaccines. Immunogenicity of the vaccine.

Área

Oncologia - Tumores Ginecológicos