Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, P.R. China.
Department of Gynecology, Hospital of Chongqing Institute of Traditional Chinese Medicine, Chongqing, P.R. China.
PLoS One. 2019 Mar 1;14(3):e0213062. doi: 10.1371/journal.pone.0213062. eCollection 2019.
Persistence of high-risk human papillomavirus (hr-HPV) infections is the most critical risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer (CC). Treatment of persistent oncogenic HPV-positive women after 12-24 months follow-up is still controversy. Detoxification therapy of Chinese medicine (DTCM) has been conducted recently. However, the conclusions are still unclear. We planned to conduct a systematic review and meta-analysis to explore DTCM in the treatment of persistent hr-HPV infections.
Nine electronic databases were systematically searched from their inception to 30 September 2018. Randomized controlled trials comparing DTCM with follow-up or placebo were included. Risk of bias was assessed by the Cochrane 'Risk of Bias' tool. Review Manager 5.3 was used for statistical analyses. Relative ratios (RR) and 95% confidence intervals were used for dichotomous data, and the mean difference (MD) was used for continuous data. We assessed the quality of trials by the GRADE.
Seventeen RCTs from 2011 to 2018 with 1906 participants were included. The evidence showed that DTCM had a pooled efficacy difference in favor of increasing the HPV clearance rate compared to placebo groups (RR = 2.62, 95% CI 1.28 to 5.33, very low quality) and follow-up groups (RR = 1.88, 95% CI 1.60 to 2.22, low quality). The median HPV persistence tended to decline from 50% within six months to 41.5% at 12 months, and 31.5% at 24 months. A significantly increased regression rate of CIN was found in the DTCM compared with placebo groups (RR = 3.61, 95% CI 1.21 to 10.83, very low quality) and follow-up groups (RR = 1.79, 95% CI 1.31 to 2.45, very low quality). Additionally, we found DTCM have an impact on TNF-α (MD = 2.99, 95% CI 1.90 to 4.07; very low quality), IFN-α (MD = 3.47, 95% CI 2.42 to 4.52; very low quality), CD4+/CD8+ cells (MD = 0.21, 95% CI 0.05 to 0.37; very low quality) compared with follow up groups in some trials with small sample sizes. The major adverse events were genital mucosal irritation symptoms (10%, 5/50).
DTCM have favorable outcomes on improving the HPV clearance rate, increasing the regression rate of CIN, and impacting the proportion of some immune cells and cytokine levels. However, most of the evidence was of low quality. Any future high-quality trials and a more extended follow-up period of 24 months or more should be performed.
持续性高危型人乳头瘤病毒（hr-HPV）感染是宫颈上皮内瘤变（CIN）和宫颈癌（CC）的最关键危险因素。对于持续存在致癌 HPV 阳性的女性，在 12-24 个月的随访后进行治疗仍然存在争议。最近已经进行了中药解毒疗法（DTCM）的治疗。然而，结论仍不清楚。我们计划进行系统评价和荟萃分析，以探讨 DTCM 在持续性 hr-HPV 感染中的治疗作用。
系统检索了从成立到 2018 年 9 月 30 日的 9 个电子数据库。纳入了比较 DTCM 与随访或安慰剂的随机对照试验。使用 Cochrane“风险偏倚”工具评估风险偏倚。使用 Review Manager 5.3 进行统计分析。二分类数据采用相对比值（RR）和 95%置信区间表示，连续性数据采用均数差（MD）表示。我们通过 GRADE 评估试验的质量。
纳入了 2011 年至 2018 年的 17 项 RCT，共有 1906 名参与者。证据表明，与安慰剂组（RR=2.62，95%CI 1.28 至 5.33，极低质量）和随访组（RR=1.88，95%CI 1.60 至 2.22，低质量）相比，DTCM 组在增加 HPV 清除率方面具有更优的疗效差异。HPV 持续存在的中位数倾向于在六个月内从 50%下降到 12 个月时的 41.5%，24 个月时的 31.5%。与安慰剂组（RR=3.61，95%CI 1.21 至 10.83，极低质量）和随访组（RR=1.79，95%CI 1.31 至 2.45，极低质量）相比，DTCM 组 CIN 的消退率显著增加。此外，我们发现 DTCM 对 TNF-α（MD=2.99，95%CI 1.90 至 4.07；极低质量）、IFN-α（MD=3.47，95%CI 2.42 至 4.52；极低质量）和 CD4+/CD8+细胞（MD=0.21，95%CI 0.05 至 0.37；极低质量）有影响，与一些样本量较小的随访组相比。主要不良事件是生殖器黏膜刺激症状（10%，5/50）。
DTCM 在提高 HPV 清除率、增加 CIN 消退率以及影响某些免疫细胞和细胞因子水平方面具有良好的效果。然而，大部分证据质量较低。未来应进行高质量的试验和更长的 24 个月或更长的随访。
