Human vaginal microbiome in cervical dysplasia and healthy controls

Shotgun metagenomic sequencing was used to taxonomically and functionally characterize the vaginal microbiota of women with and without cervical dysplasia. Study participants were recruited between June 2017 and January 2020. Women with histologically verified dysplasia and cancer (n = 177; low grade dysplasia (LSIL) n=81, high-grade dysplasia (HSIL) n= 94, cancer n=2) were recruited at the gynaecological out-patient clinic at Uppsala University hospital, Sweden. Healthy controls were recruited by sending invitations by regular mail to all women invited to the organized cervical screening programme in Uppsala County, Sweden (VaMiGyn study). Women were selected as controls from the VaMiGyn study based on having two consecutive normal screening tests, and no abnormal cervical pathology, including histology, cytology and HPV, during the full duration of the study period (n= 177). Women with dysplasia had a higher vaginal microbial diversity, and higher abundances of Gardnerella vaginalis, Aerococcus christensenii, Peptoniphilus lacrimalis and Fannyhessea vaginae, while healthy controls had higher relative abundance of Lactobacillus crispatus. Genes involved in e.g. nucleotide biosynthesis and peptidoglycan biosynthesis were more abundant in women with dysplasia. Healthy controls showed higher abundance of genes important for e.g. amino acid biosynthesis, (especially L-lysine) and sugar degradation. These findings suggest that the microbiota may have a role in creating a pro-oncogenic environment in women with dysplasia. Its role and potential interactions with other components in the microenvironment deserve further exploration.