Title Vaginal Microbiome Dysbiosis is Associated with the Different Cervical Disease Status
Author Yingying Ma1†, Yanpeng Li1†, Yanmei Liu2,3, Le Cao1, Xiao Han2,3, Shujun Gao2,3*, and Chiyu Zhang1*
Address 1Shanghai Public Health Clinical Center, Fudan University, Shanghai 200437, People’s Republic of China, 2Center of Diagnosis and Treatment for Cervical and Uterine Cavity Disease, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, People’s Republic of China, 3Shanghai Key Laboratory of Female Reproductive Endocrine‑Related Disease, Fudan University, Shanghai 200011, People’s Republic of China
Bibliography Journal of Microbiology, 61(4),423-432, 2023,
DOI 10.1007/s12275-023-00039-3
Key Words Vaginal microbiome · Cervical cancer · Dysbiosis · Disease status · HPV
Abstract Vaginal microbiome composition was demonstrated to be associated with cervical disease. The colonization characteristics of vaginal microbes and their association with the different cervical disease status, especially cervical cancer (CC), are rarely investigated. In this cross-sectional study, we characterized the vaginal microbiome of women with different status of cervical diseases, including 22 NV + (normal tissue with HPV infection), low-grade squamous intraepithelial lesion (LSIL, n = 45), high-grade squamous intraepithelial lesion (HSIL, n = 36) and CC (n = 27) using bacterial 16S DNA sequencing. Thirty HPV-negative women with normal tissue were used as the control group. We found that higher diversity of microbiome with gradual depletion of Lactobacillus, especially L. crispatus, was associated with the severity of cervical disease. High-risk HPV16 infection was associated with higher microbiome diversity and depletion of Lactobacillus in high-grade cervical diseases (i.e. HSIL and CC). The CC group was characterized by higher levels of Fannyhessea vaginae, Prevotella, Bacteroides, Finegoldia, Vibrio, Veillonella, Peptostreptococcus, and Dialister. Co-occurrence network analyses showed that negative correlations were exclusively observed between Lactobacillus and other bacteria, and almost all non-Lactobacillus bacteria were positively correlated with each other. In particular, the most diverse and complex co-occurrence network of vaginal bacteria, as well as a complete loss of L. crispatus, was observed in women with CC. Logistic regression model identified HPV16 and Lactobacillus as significant risk and protective factors for CC, respectively. These results suggest that specific Lactobacillus species (e.g. L. crispatus and L. iners) can be used as important markers to target prevention measures prioritizing HPV16-infected women and other hrHPV-infected women for test, vaccination and treat initiatives.