Abstract
BACKGROUND: Persistent high-risk human papillomavirus (HR-HPV) infection is the key driver of cervical cancer, yet current management strategies are often invasive or limited to watchful waiting. Kushen gel, derived from Sophora flavescens, has shown promise in promoting viral clearance, but clinical evidence remains inconsistent. This meta-analysis aimed to evaluate the efficacy and safety of Kushen gel in women with HR-HPV infection. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and SinoMed databases from inception to September 2025 for randomized controlled trials (RCTs) evaluating Kushen gel in women with cervical HR-HPV infection. Eligible studies compared Kushen gel, either alone or in combination with interferon, loop electrosurgical excision (LEEP), or microwave therapy, against control interventions (follow-up or interferon). The primary outcome was HPV clearance, with secondary outcomes including viral load, recurrence, and adverse events. Subgroup analyses were prespecified according to treatment regimen, disease type, follow-up duration, and sample size. The risk of bias was assessed with the Cochrane tool, and certainty of evidence was evaluated using GRADE. Data were synthesized with random- or fixed-effects models depending on heterogeneity. RESULTS: Nine RCTs involving 872 women were included. Pooled analysis showed that Kushen gel-based interventions significantly improved HPV clearance compared with controls (RR = 1.51, 95% CI 1.28-1.78), with consistent benefits across treatment regimens, disease types, follow-up durations, and study sizes. Kushen gel also significantly reduced HPV viral load (MD = -0.70, 95% CI -0.85 to -0.56), recurrence (OR = 0.21, 95% CI 0.09-0.52), and vaginal bleeding (OR = 0.29, 95% CI 0.14-0.60). Reported adverse events were mild and self-limiting, with no major between-group differences. Sensitivity analyses confirmed the robustness of the findings, whereas the GRADE certainty of evidence for HPV clearance was rated as low. CONCLUSION: Kushen gel significantly enhances HPV clearance and reduces recurrence with a favorable safety profile, supporting its potential as a non-invasive therapeutic option for women with HR-HPV infection. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD420251150231.