Association of Cervical Microbial Community with Persistence, Clearance and Negativity of Human Papillomavirus in Korean Women: a Longitudinal Study

The present study aimed to identify the cervical microbes that are associated with HPV negativity, HPV clearance and HPV persistence and to assess the microbes' longitudinal associations as related to HPV infection dynamics among Korean women. We enrolled 41 women with 107 samples, and classified them according to the HPV infection dynamics: HPV negativity (21 samples, 10 subjects), HPV clearance (42 samples, 15 subjects), and HPV persistence (44 samples, 16 subjects). Cervical swabs were collected at the baseline and six-month-interval follow-up visits. HPV positivity was determined by HPV DNA HC2 assay, and the microbiome was analyzed using 16SrRNA pyrosequencing, linear discriminant analysis effect size and multivariate logistic analysis. In the multivariate logistic analysis results, Lactobacillus crispatus (multivariate OR (mOR) = 8.25, 95% CI 2.13~32.0) was predominant in the HPV-negative group. We observed that Eubacterium eligens (mOR = 11.5, 95% CI 1.31~101.4), Gardnerella vaginalis (mOR = 17.0, 95% CI 2.18-131.8), and Ureaplasma urealyticum (mOR = 7.42, 95% CI 1.3-42.46) had the strongest associations with HPV clearance, and Lactobacillus johnsonii (mOR = 16.4, 95% CI 1.77-152.2) with HPV persistence. Overall, greater diversity was observed in HPV-persistence than in HPV-negative women. Our findings suggest that the presence and prevalence of a specific cervical microbiome are factors involved in HPV dynamics.