Risk factors for persistent high-risk HPV infection and recurrence burden of vaginal infections in women with cervical low-grade squamous intraepithelial lesions: a retrospective cohort study.
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BACKGROUND: Persistent high-risk human papillomavirus (HR-HPV) infection drives cervical carcinogenesis, yet factors determining persistence in women with low-grade squamous intraepithelial lesions (LSIL) remain incompletely characterized. The longitudinal recurrence burden of vaginal infections including aerobic vaginitis, bacterial vaginosis, and vulvovaginal candidiasis in this population has not been systematically quantified. OBJECTIVE: To identify independent risk factors for persistent HR-HPV infection and evaluate the recurrence burden of aerobic vaginitis, bacterial vaginosis, and vulvovaginal candidiasis in women with cervical LSIL. STUDY DESIGN: This retrospective cohort study included 3,563 women with cervical LSIL who underwent concurrent vaginal microecology testing, HPV genotyping, and cervical cytology at Guangdong Women and Children Hospital (January 2021-August 2025). Patients were classified as persistent (n=919; ≥365 days with the same HR-HPV subtype) or transient (n=2,644; >30 days and <365 days). Multivariate logistic regression identified factors associated with persistence. Negative binomial regression assessed recurrence burden, expressed as incidence density per 100 person-years. RESULTS: After adjustment, age (per 5 years: OR = 1.13, 95% CI: 1.09-1.17, P<0.001), HPV-52/58 (OR = 1.65, 95% CI: 1.38-1.98, P<0.001), and multiple HR-HPV infections (OR = 1.50, 95% CI: 1.24-1.81, P<0.001) independently predicted persistence. Bacterial vaginosis (OR = 0.69, 95% CI: 0.55-0.88, P = 0.002) and intermediate bacterial vaginosis (OR = 0.66, 95% CI: 0.52-0.84, P<0.001), and vulvovaginal candidiasis (OR = 0.75, 95% CI: 0.58-0.96, P = 0.024) showed inverse associations. Among persistently infected women, aerobic vaginitis had the highest recurrence burden (35.77 per 100 person-years, 95% CI: 33.17-38.53), exceeding bacterial vaginosis and vulvovaginal candidiasis. Persistent infection was associated with TCT abnormalities ≥ASC-US (OR = 1.63, 95% CI: 1.40-1.91, P<0.001) and LSIL+ lesions (OR = 1.48, 95% CI: 1.25-1.75, P<0.001). CONCLUSION: HPV-52/58, multiple HR-HPV infections, and advancing age significantly increase persistence risk in LSIL patients. The inverse associations of bacterial vaginosis and vulvovaginal candidiasis with persistence are likely non-causal and should be interpreted with caution. The high aerobic vaginitis recurrence burden underscores the need for integrated management addressing both viral persistence and vaginal dysbiosis. These findings support genotype- and microbiota-informed risk stratification.