BACKGROUND: Ureaplasma parvum (U. parvum) is generally regarded as innocuous, and studies focusing on variations in pathogenicity among U. parvum serovars are inadequate. We elucidated the variations in the pathogenicity of U. parvum serovars in promoting human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN). METHODS: This cross-sectional study used baseline data from a Chinese multicenter prospective cohort of women of childbearing age undergoing routine cervical cancer screening. We employed multivariate logistic regression analysis to estimate the pathogenic effects of specific U. parvum serovars on HPV infection and CIN. Causal mediation analysis was performed to ascertain the direct effects of specific U. parvum serovars on CIN and their indirect implications via HPV infection. FINDINGS: The final data analysis encompassed 7058 participants. Upon adjusting for confounding factors, a positive association was observed between U. parvum serovars 1, 3, and 6 and HPV infection (OR 1.53, 95%CI 1.15-2.03
OR 1.31, 95%CI 1.06-1.64
OR 2.34, 95%CI 1.90-2.87)
however, only participants with U. parvum serovar 6 showed an increased risk of CIN (OR 1.90, 95%CI 1.19-3.02). No substantial correlation was observed between U. parvum serovar 14 and HPV or CIN incidence. HPV infection potentially mediates the influence of U. parvum serovar 6 on CIN, with a mediation proportion of 76.66%. INTERPRETATIONS: Our findings suggest that different U. parvum serovars vary in pathogenicity regarding HPV and CIN. Early detection of specific U. parvum serovars, such as U. parvum serovar 6, in HPV-infected individuals may enable early intervention therapies and reduce the risk of CIN development.