Abstract

Objective: To investigate the characteristics of cervical microbiota in patients with HPV (Human Papillomavirus) infection, and to analyze the associations of cervical microbiota and HPV infection or cervicitis. Methods: 300 samples underwent HPV nucleic acid testing was collected in this case-control study from June 2019 to April 2020 in the Zhujiang Hospital of Southern Medical University, there were 150 cases allocated in HPV infection group (HPV+), and 150 cases of negative nucleic acid test were non-infectious Group (HPV-). Next-generation sequencing was used to sequence the V4 region of the bacterial 16S rRNA gene, and QIIME pipeline was used to analysis the microbiota composition of the two groups. Wilcoxon rank sum test and Kruskal-Wallis test were used to statistically analysis the differences of the microbiota between groups; and the α diversity and β diversity of the flora between groups were statistically analyzed by Adonis multivariate analysis of variance and Wilcoxon rank sum test. Results: A total of 300 samples were analyzed in this study, of which 150 samples were HPV-positive and 150 samples were HPV-negative; among HPV-positive cases, 132 were infected by high-risk HPV (88.0%), and 18 were low-risk HPV infections (12.0%). The composition of the cervical microbiota were significantly different between the HPV+group and the HPV-group, which in the HPV+group, the α diversity of the cervical microbiota were significantly increased (Shannon index, W=8 174, P<0.000 1; PD whole tree, W=8 887, P=0.001 7). The β diversity of the two groups was significantly different (Binary Jaccard, F=2.325 4, P=0.042 0; Bray Curtis, F=2.136 44, P=0.044 0). The relative abundance of Lactobacillus spp. and L.iners in the HPV+group sample decreased significantly (W=7 730, P<0.000 1; W=8 979, P=0.002 5), accompanied by enriched Achromobacter, Stenotrophomonas, Methylobacterium, Sneathia and Dialister. There was no significant difference in the composition of the cervical microbiota between high-risk HPV infection and low-risk HPV infection (F=4.100 4, P>0.05). In addition, cervicitis is significantly related to HPV infection (χ²=19.78, P<0.000 1), the composition of cervical flora has similarity features in cervicitis and HPV infection samples. Compared with the normal group, the cervical microbiota of cervicitis with HPV infection is mainly enriched in Achromobacter, Aerococcaceae, Streptococcus, Fusobacteria, and Xanthomonadaceae. Conclusion: The cervical microbiota of patients with HPV infection has a significant dysbiosis, with increased diversity and significant depletion of lactobacillus, accompanied by an increase in the abundance of pathogenic bacteria such as Achromobacter.

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