Date Published: March 1, 2019
Publisher: Public Library of Science
Author(s): Mei Luo, JiaJie Yu, ShuYi Zhu, Li Huang, Yu Chen, ShaoBin Wei, Qinhong Zhang.
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.
High-risk human papillomavirus (hr-HPV) infection is the primary risk factor of cervical cancer (CC) and its precancerous cervical intraepithelial neoplasia (CIN) [1, 2]. It is one of the six human viruses which has been classified by the International Agency for Research on Cancer (IARC) as Group 1 (carcinogenic to humans) . Although hr-HPV infection is prevalent in sexually active women, typically transient and cleared within months to 2 years [4, 5], a few cervical infections still persistent and progress to CC. A prospective study among 3282 women in the Netherlands reported that approximately 34% of young women fail to clear HPV in 2 years . In mainland China, the reported persistent infection rate among women (ages 16–69) was 13.30–22.94% [7–9].
We followed the reporting standards for systematic reviews and meta-analyses of randomized controlled trials according to PRISMA statements. The protocol has been registered with the Prospective Registration of Systematic Reviews (PROSPERO) (Number CRD42018092712).
The initial search of electronic databases retrieved 1347 trials. After title and abstract reading, 259 trials were potential eligibility; 17 trials published in Chinese from 2011 to 2018 were identified finally [18–34] after reading the full text (Fig 1).
This study systematically reviewed the existing evidence about investigating the efficacy of DTCM in the treatment of persistent hr-HPV infections. Currently, treatment of persistent oncogenic HPV-positive women after 12–24 months follow-up has been the focus of controversy. In addition to its advantages of more abundant sources and lower prices, Chinese material medicine is a critical component of TCM and has been practiced for thousands of years in China. Many molecules extracted from herbs and natural products have been found in the laboratory to be potential to prevent cancer . Chinese medicine was reported to block the expression of E6, E7 gene in HPV16, regulating immune function in cell and animal study . However, epidemiological literature regarding whether DTCM effectively cleans hr-HPV and prevents CC from happening is limited.
Detoxification therapy of Chinese medicine appears to have favorable effects on improving the rate of HPV clearance, increasing the regression rate of CIN, and impacting the proportion of some immune cells and cytokine levels in the genital tract after treatment. The median HPV persistence tended to decrease with increasing follow-up time. However, due to the poor methodological quality and high heterogeneity of the included trials, our conclusions should be carefully interpreted. Any future high-quality evidence trials should elaborate with a rigorously designed large study sample method and determine both the cost-efficacy of different interventions and the impact of DTCM on the quality of life of patients. A longer follow-up period of 24 months or more should be performed in the future.