A Real-World Cohort Study on the Efficacy of a Black Raspberry Extract-Containing Composite Gel in Clearing Persistent High-Risk Human Papillomavirus Infection of the Cervix

Objective: To evaluate the efficacy of a black raspberry extract-containing composite gel in treating persistent cervical high-risk human papillomavirus (hrHPV) infection and to analyze the clinical factors influencing treatment outcomes, with the goal of informing precision treatment strategies for this population.Methods: This was a prospective cohort study that enrolled 161 patients with persistent hrHPV infection. Participants received vaginal applications of a black raspberry gel every other day (discontinued during menstruation) for three consecutive months, followed by a three-month off-treatment period before re-examination. The primary efficacy endpoint was the viral clearance rate, defined as the clearance of any high-risk HPV subtype that was positive at baseline. Univariate analysis was performed to evaluate the correlation between clinical characteristics and efficacy. Additionally, data from 121 contemporaneous patients who received other treatments were retrospectively collected, and after propensity score matching, the efficacy was compared between the two groups.Results: The response rate among 161 patients who received black raspberry gel intervention was 50.9% (82/161). Univariate analysis showed that significantly higher response rates were observed in younger patients (P=0.011) and those who were premenopausal (P=0.003). Patients with multiple HPV infections had a significantly higher response rate compared to those with single infections (P=0.043). The clearance rates for HPV16 and HPV18 were 66.7% and 70.0%, respectively. No serious adverse events were reported during the intervention period. After propensity score matching, 99 patients were matched in the black raspberry gel group and 99 in the concurrent alternative treatment group. The response rate in the black raspberry gel group (57.6%, 57/99) was non-inferior to that in the concurrent alternative treatment group (55.6%, 55/99). Subtype analysis revealed that the black raspberry gel achieved a significantly higher clearance rate for hrHPV types 16, 18, 33, 39, 51, and 59 compared to the concurrent alternative treatment group (61.5% vs. 31.3%, P=0.011). For hrHPV types 52, 53, 58, and 68, the overall clearance rate was comparable between the black raspberry gel group and the concurrent alternative treatment group (51.0% vs. 50.0%, P=1.000). However, for hrHPV types 31, 35, 56, 66, and 73, the overall clearance rate was significantly lower in the black raspberry gel group than in the concurrent alternative treatment group (39.1% vs. 69.6%, P=0.038).Conclusion: The black raspberry extract-containing composite gel demonstrated a favorable safety profile and certain clinical efficacy in patients with persistent hrHPV infection, particularly showing enhanced effectiveness in younger, premenopausal women and exhibiting potential advantages in clearing high-risk subtypes such as HPV16/18. This study provides new real-world evidence for topical pharmacotherapy in persistent hrHPV infection and offers a preliminary theoretical basis for developing individualized, subtype-specific precision intervention strategies in the future.