Abstract
INTRODUCTION: With the expansion of cervical cancer screening in China, clarifying the epidemiology of high-risk human papillomavirus (HR-HPV) and co-infecting reproductive tract bacterial pathogens in underserved regions is increasingly important. We investigated the prevalence and co-infection patterns of HR-HPV and bacterial pathogens (Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae) among rural women in Hainan, and examined their associations with cervical epithelial lesions to inform optimized risk stratification for this population. METHODS: Within a screening cohort of 8,925 women in Hainan (May-October 2025), we employed a nested case-control design enrolling 869 HR-HPV-positive cases and 473 negative controls, which were randomly selected from HR-HPV-negative women, with age adjustment applied in statistical analyses. Participants underwent genotyping for HR-HPV and bacterial sexually transmitted infections (C. trachomatis, U. urealyticum, N. gonorrhoeae). Cervical abnormalities were assessed via ThinPrep Cytologic Test and subsequent histopathology. RESULTS: HR-HPV infection was associated with older age and lower educational attainment (p < 0.001). Among HR-HPV subtypes, single-type HR-HPV infection predominated (83.08%). U. urealyticum was the most prevalent reproductive tract bacterial pathogen (45.75%) and was more frequently co-detected in HR-HPV-positive women than in controls (p < 0.001). Network analysis further identified U. urealyticum as a central hub, showing strong co-occurrence with HR-HPV52 and HR-HPV58. Clinically, C. trachomatis was independently associated with higher odds of atypical squamous cells of undetermined significance (aOR = 2.82, p = 0.025), whereas U. urealyticum was associated with an increased risk of cervical intraepithelial neoplasia grade 1 (aOR = 1.79, p = 0.040). CONCLUSION: This study highlights a distinct co-infection ecosystem centered on U. urealyticum in rural women, where C. trachomatis and U. urealyticum drive differentiated risks for early cervical lesions. Consequently, public health strategies should prioritize this underrepresented rural population. Integrating targeted bacterial STIs testing into HPV screening could significantly enhance risk stratification and intervention efficiency in settings with limited resources.