目标:尽管广泛的预防性疫苗接种,宫颈癌仍然是一个主要的健康问题,死亡率相当高。目前,目前正在评估HPV相关宫颈恶性肿瘤的治疗性疫苗作为标准治疗的潜在补充.
目的:本系统综述采用随机对照试验(RCTs)研究治疗性疫苗对2、3级宫颈癌及宫颈上皮内瘤变(CIN)患者的治疗效果。
方法:PubMed,Embase,并检索了Cochrane中央对照试验注册数据库。只选择了截至2024年1月31日发表的英文文章。此外,手动搜索选定的原始论文和最近的评论文章的参考列表,以寻找其他来源。从选定的文章中提取研究特征的数据。对感兴趣的结果数据进行了综合,和疫苗功效终点(组织学病变消退,临床反应,和总生存期)被选为分组研究的基础。
结果:筛选831篇文章后,纳入了9个RCT,有800名参与者,其中有677名参与者的7项研究涉及CIN2和CIN3,并检查了病变消退至≤CIN1作为疗效终点。其中两项研究的结果被认为有很高的偏倚风险,另一个不包含统计分析。其他四项研究的结果是定量合成的,并且p值的合并显示疫苗组和安慰剂组在病变消退方面存在显着差异(RCT中的p值分别为0.135、0.049和0.034,产生的组合p值为0.010)。证据的确定性被评为中等。在两个RCT中研究了晚期宫颈癌患者,有123名参与者。以临床反应和总生存期为终点,结果报告为不显著.这些结果的证据的确定性被评为非常低,主要是由于事件数量很少。所有研究都报告了对疫苗的良好耐受性。
结论:结果表明治疗性疫苗在CIN2和CIN3病变消退中的潜力。此外,关于晚期宫颈癌患者的RCTs数量非常低,目前发现了一个潜在的证据缺口.
OBJECTIVE: Despite widespread prophylactic vaccination, cervical cancer continues to be a major health problem with considerable mortality. Currently, therapeutic vaccines for HPV-associated cervical malignancies are being evaluated as a potential complement to the standard treatment.
OBJECTIVE: The present systematic review was conducted on randomized controlled trials (RCTs) to investigate the effects of therapeutic vaccines on the treatment of patients with cervical cancer and cervical intraepithelial neoplasia (CIN) of Grades 2 and 3.
METHODS: The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched. Only articles in English published up until 31 January 2024 were selected. Also, reference lists of the selected original papers and recent review articles were manually searched for additional sources. Data on study characteristics were extracted from the selected articles. Data on outcomes of interest were synthesized, and vaccine efficacy endpoints (histological lesion regression, clinical response, and overall survival) were selected as the basis for grouping the studies.
RESULTS: After screening 831 articles, nine RCTs with 800 participants were included, of which seven studies with 677 participants involved CIN2 and CIN3 and examined lesion regression to ≤CIN1 as the efficacy endpoint. Results of two of these studies were deemed to have a high risk of bias, and another one did not contain statistical analyses. Results of the other four studies were quantitively synthesized, and the pooling of p-values revealed a significant difference between the vaccine and placebo groups in terms of lesion regression (p-values of 0.135, 0.049, and 0.034 in RCTs, yielding a combined p-value of 0.010). The certainty of the evidence was rated as moderate. Patients with advanced cervical cancers were studied in two RCTs with 123 participants. Clinical response and overall survival were taken as endpoints, and the results were reported as not significant. The certainty of the evidence of these results was rated as very low, mainly due to the very small number of events. All studies reported good tolerance for the vaccines.
CONCLUSIONS: The results indicate the potential for therapeutic vaccines in the regression of CIN2 and CIN3 lesions. Moreover, a potential gap in evidence is identified regarding the very low number of RCTs in patients with advanced cervical cancer.