Despite the knowledge that HPV is responsible for high-grade CIN and cervical cancer, little is known about the use of therapeutic vaccines as a treatment. We aimed to synthesize and critically 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. A systematic review of clinical trials adhering to the PRISMA 2020 statement in MEDLINE/PubMed, Embase, CENTRAL Cochrane, Web of Science, Scopus, and LILACS was undertaken, with no data or language restrictions. Primary endpoints related to the safety, efficacy, and immunogenicity of these vaccines were assessed by reviewing the adverse/toxic effects associated with the therapeutic vaccine administration via histopathological regression of the lesion and/or regression of the lesion size and via 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. A total of 1184 studies were identified, and 16 met all the criteria. Overall, the therapeutic vaccines were heterogeneous regarding their formulation, dose, intervention protocol, and routes of administration, making a meta-analysis unfeasible. In most studies (n = 15), the vaccines were safe and well tolerated, with clinical efficacy regarding the lesions and histopathological regression or viral clearance. In addition, eleven studies showed favorable immunological responses against HPV, and seven studies showed a positive correlation between immunogenicity and the clinical response, indicating promising results that should be further investigated. In summary, therapeutic vaccines, although urgently needed to avoid progression of CIN 2/3 patients, still present sparse data, requiring greater investments in a well-designed phase III RCT.
尽管已知HPV是导致高级别宫颈上皮内瘤变（CIN）及宫颈癌的病因，但关于治疗性疫苗作为治疗手段的应用仍知之甚少。本研究旨在系统整合并严格评估临床试验中关于HPV相关高级别CIN患者治疗性疫苗的安全性、有效性及免疫原性的证据。我们依据PRISMA 2020声明，在MEDLINE/PubMed、Embase、CENTRAL Cochrane、Web of Science、Scopus及LILACS数据库中进行了系统性文献综述，未设置数据或语言限制。通过分析治疗性疫苗接种相关的不良/毒性反应、病灶的组织病理学消退和/或病灶体积缩小、病毒清除情况，以及比较接种者与未接种者（或接种前后）的免疫应答，评估了疫苗安全性、有效性与免疫原性等主要终点指标。初筛共获得1184项研究，其中16项符合全部纳入标准。总体而言，各疫苗在配方、剂量、干预方案及给药途径方面存在显著异质性，导致无法进行荟萃分析。在大多数研究（15项）中，疫苗安全性良好且耐受性佳，在病灶消退、组织病理学逆转或病毒清除方面显示出临床有效性。此外，11项研究显示疫苗能诱导针对HPV的有利免疫应答，7项研究表明免疫原性与临床反应呈正相关，这些结果提示治疗性疫苗具有良好前景，值得进一步研究。总之，虽然治疗性疫苗对阻止CIN 2/3患者病情进展具有迫切需求，但目前相关数据仍显不足，亟需在精心设计的III期随机对照试验中加大投入。
肿瘤(癌症)患者之家