Cervical cancer (CC) is the second most common cancer in females in developing countries. The two viral oncoproteins E6 and E7 mediate the oncogenic activities of high-risk human papillomavirus (HR-HPV), and HR-HPV, especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through different pathways. microRNAs (miRNAs) may be associated with CC pathogenesis. Researches have indicated that human papillomavirus (HPV) may regulate cellular miRNA expression through viral E6 and E7. Herein, the purposes of this study were to identify the relationship between HPV infection and aberrantly expressed miRNAs and to investigate their pathogenic roles in CC. miRNA expression was assessed using a microRNAs microarray in HPV16 E6- and E7-integrated HPV-negative HT-3 cell lines and mock vector-transfected HT-3 cells. The microarray results were validated, and the expression of miR-3156-3p was identified in HPV-positive and -negative CC cell lines as well as primary CC and normal cervical epithelium tissues using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8), flow cytometry, transwell analysis, tube formation, and Western blotting were used to identify the functional role of miR-3156-3p in CaSki, SiHa, and HeLa cell lines. Six underexpressed microRNAs (miR-3156-3p, 6779-3p, 4779-3p, 6841-3p, 454-5p and 656-5p) were consistently identified in HPV16 E6- and E7-integrated HT-3 cells. Further investigation confirmed a significant decrease of miR-3156-3p in HPV16/18 positive CC lesions. CCK8, flow cytometry, transwell analysis, tube formation assays, and Western blotting of the CC cell lines with miR-3156-3p over/under-expression in vitro showed that miR-3156-3p was involved in cell proliferation, apoptosis, migration, neovascularization, and SLC6A6 regulation. Our findings indicate that miR-3156-3p plays a suppressor-miRNA role in CC and that its expression is associated with HR-HPV infection.

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.