Distinction Between Vaginal and Cervical Microbiota in High-risk Human Papilloma Virus-infected Women in China

Background: High-risk human papilloma virus (hrHPV) is the main causal factor of cervical precancer and cancer when persistent infection is left untreated. Previous studies have confirmed the vaginal microbiota is associated with HPV infection and the development of cervical lesions. The microbiota at different parts of the female genital tract is closely related but different from each other. To analyze the distinction between the vaginal and cervical microbiota of hrHPV(+) women in China, one hundred subjects were recruited, including 10 patients with HPV16/18(+) and cervical carcinoma, 38 patients with HPV16/18(+) but no cervical carcinoma, 32 patients with other hrHPV(+) and 20 healthy controls with HPV(-). Vaginal and cervical microbiota were separately tested through next-generation sequencing (NGS) targeting the variable region (V3-V4) of the bacterial ribosome 16S rRNA gene.

Results: HrHPV(+) subjects had higher percentages of vaginal douching history (P = 0.001), showed more frequent usage of sanitary pads (P = 0.007), had more sex partners (P = 0.047), were more sexually active (P = 0.025) and more diversed in ways of contraception (P = 0.001). The alpha diversity of the cervical microbiota was higher than that of the vagina. The cervical microbiota consisted of a lower percentage of Firmicutes and a higher percentage of Proteobacteria than the vagina at the phylum level. Sphingomonas, belonging to α-Proteobacteria, was almost below the detection limit in the vagina but accounted for five to 10 % of the bacteria in the hrHPV(-) cervix (P<0.001) and was inversely associated with hrHPV infection (P<0.05). Pseudomonas, belonging to γ-Proteobacteria, could hardly be seen in the normal vagina and shared a small percentage in the normal cervix but was significantly higher in the HPV16/18(+) (P<0.001) and cancerous cervix (P<0.05). No significant difference was shown in the percentage of BV associated anaerobes, like Gardnerella, Prevotella, Atopobium and Sneathia, between the cevix and vigina.

Conclusions: The proportion of Proteobacteria was significantly higher in the cervical microbiota than that of vagina. The hrHPV infection and cervical cancer was positively associated with Pseudomonas and negatively associated with Sphingomonas. It is of great improtance to deeply explore the cervical microbiota and its function in cervical cacinogenesis.