Abstract
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.
Highlights
Cervical cancer is one of the leading causes of cancer death among women, and the most important causal agent in the development of cervical intraepithelial neoplasia (CIN) and cervical cancer is persistent infection with high-risk human papilloma virus[1,2,4,5]
We enrolled 41 women and classified them into three human papillomavirus (HPV) groups according to the HPV infection dynamics: HPV negativity (21 samples, 10 subjects), HPV clearance (42 samples, subjects), and HPV persistence (44 samples, subjects)
The sequence reads were assigned to 14.5 operational taxonomic units (OTUs) in HPV negativity, 20.2 OTUs in HPV clearance, and 24.5 OTUs in HPV persistence
Summary
Cervical cancer is one of the leading causes of cancer death among women, and the most important causal agent in the development of cervical intraepithelial neoplasia (CIN) and cervical cancer is persistent infection with high-risk human papilloma virus (hrHPV)[1,2,4,5]. There is evidence that most cases of HPV infection are transient, which is to say, likely to regress naturally[3] Several cofactors such as smoking, high parity, long-term use of oral contraceptives[6], hormone treatment and co-infection with sexually transmitted infection agents are relevant to progression of cervical cancer among HPV-infected women[7]. Notwithstanding the many reports on cervical microbes and their HPV associations[13,14], more knowledge on the epidemiology and longitudinal dynamics of cervical microbes is required before the nature of HPV progression is clearly understood. 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 with HPV infection dynamics among Korean women. Demographic characteristics Age (years) HPV, viral load); Median (range) Body mass index (Kg/m2) Parity(parous) Postmenopausal status Oral contraceptive use (ever) HRT Never Ever Smoking status Never Ever Passive smoking No yes Alcohol drinking status Yes No Alcohol drinking (>1 week)
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