Objectives Although persistent human papillomavirus (HPV) infection is a major cause of cervical squamous intra-epithelial neoplasia, the relationship between vaginal microbiota and different grades of squamous intra-epithelial neoplasia is not well established. We explored the possible relationship between the vaginal microbiota and the progression of cervical squamous intra-epithelial neoplasia.
Methods We evaluated 69 women who attended the Obstetrics and Gynecology Hospital of Fudan University. The vaginal bacterial composition of three groups of women was characterized by deep sequencing of bar-coded 16S rRNA gene fragments (V3–4) using Illumina MiSeq. Exclusion criteria were any previous hysterectomy, history of cervical or other lower genital cancer, and/or destructive therapy of the cervix. Women who had autoimmune disorders, who were HIV positive, who received antibiotics within 15 days of sampling, or who had engaged in sexual intercourse or douching within 48 hours prior to sampling were also excluded. P values for age and proportions of organisms were calculated using one-way ANOVA and p values for HPV status and community state types (CSTs) were calculated using a χ2 test.
Results The vaginal bacterial composition of three groups of women, those without an intra-epithelial lesion or malignancy (n=31), those with a low-grade squamous intra-epithelial lesion (LSIL) (n=22), and those with a high-grade squamous intra-epithelial lesion (HSIL) (n=16) were analyzed. Lactobacillus was the most dominant genus overall. Prevotella and Streptococcus were increased in the HSIL group. Cervical disease progression was associated with the prevalence of high-risk HPV infection. Squamous intra-epithelial neoplasia converted the vaginal bacterial community structure from CSTs IV to II. Microbiota diversity was more pronounced in CST types II and IV (p<0.001), especially in type II. We found a significant enrichment in the Peptostreptococcaceae family, Pseudomonadales order, and other types of bacteria in the group of women without intra-epithelial lesions or malignancy compared with women with squamous intra-epithelial neoplasia. We found enrichment in Delftia in the LSIL and HSIL groups compared with the group without an intra-epithelial lesion or malignancy.
Conclusions Our results show that the vaginal microbiota is directly or indirectly related to the progression of squamous intra-epithelial neoplasia, and Delftia might be a microbiological hallmark of cervical pre-cancerous lesions.
- cervical cancer
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MW and JG contributed equally.
Contributors All authors contributed to the conception or design of the work, or the acquisition, analysis or interpretation of data.
Funding This work was supported by the National Nature Science Foundation of China (grant number 81873970), the Shanghai Municipal Health Bureau (grant number 20174Y0199), and the Shanghai Science and Technology Commission (grant number 19411960100).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval Ethical approval was obtained from the Ethics Committee of the Affiliated Obstetrics and Gynecology Hospital of Fudan University (no. 2019-91). All patients have signed an informed consent.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available in a public, open access repository. The patient data came from the Obstetrics and Gynecology Hospital of Fudan University.