Distinction between vaginal and cervical microbiota in high-risk human papilloma virus infected women in China
Abstract Background: High-risk human papilloma virus (hrHPV) is regarded as the main causal factor of cervical precancer and cancer when persistent infection is left untreated. Previous researches have confirmed that the vaginal microbiota was associated with HPV infection and the development of cervical lesions. A very recent study has revealed the microbiota at different parts of the female genital tract was closely related but different from each other. To analyze the distinction between vaginal and cervical microbiota of hrHPV(+) women in China, one hundred subjects were recruited including 20 healthy controls without HPV infection, 32 with other hrHPV(+), 38 with HPV16/18(+) and 10 with cervical carcinoma. Vaginal and cervical microbiota were separately tested through next-generation sequencing technology (NGS) targeting the variable region (V3-V4) of bacterial ribosome 16S rRNA gene. Results: HrHPV(+) subjects tend to be accustomed to vaginal douching (p =0.001), show more frequent usage of sanitary pads (p =0.007), have more sex partners (p =0.047), be more sexually active (p =0.025) and more diversed in ways of contraception (p =0.001). Alpha diversity of cervical microbiota was higher than that of vagina. Cervical microbiota consisted a lower percentage of Firmicutes and a higher percentage of Proteobacteria compared to the vagina at the phylm level. Sphingomonas of α-Proteobacteria was almost below detection limit in the vagina whereas accounted for five to ten percent at hrHPV(-) cervix (P<0.001) and reversely associated with hrHPV infection (P<0.05). Pseudomonas of γ-Proteobacteria could hardly be seen in the normal vagina and shared a little bit percentage in the normal cervix, but significantly higher in the HPV16/18 infected (P<0.001) and cancerous cervix (P<0.05). BV associated anaerobes like Gardnerella, Prevotella, Atopobium and Sneathia did not exhibit cervical specificity.Conclusions: Cervical microbiota has its uniqueness from that of vagina in bacterial communities presenting a higher proportion of Proteobacteria, of which Pseudomonas is positively while Sphingomonas was negatively associated with hrHPV infection and cervical cancer. It is of great improtance to deeply explore the cervical microbiota of hrHPV infected women.