Dysbiosis of Cervical and Vaginal Microbiota Associated With Cervical Intraepithelial Neoplasia

Abstract

Cervical intraepithelial neoplasia (CIN) is a precancerous condition inducing local lesions on the surface of the squamocolumnar junction of the cervix. Despite the role of vaginal microbiota having been under-discussed, the role of the cervical microbiome and the microbial migration across the reproductive tract involved in CIN was limitedly studied. We aimed to synchronously characterize the dysbiosis associated with CIN in both the cervix and vagina in a Chinese population. Profiling of cervical and vaginal microbiota from 60 CIN women and 60 healthy women was conducted. 16S rRNA sequencing was adopted. By comparing the microbial profiles between different parts of the reproductive tract, our results demonstrated an increased shift of microbial diversity in the cervix compared with that in the vagina for the CIN patients, specifically in CIN 1. Less dysbiosis was found between the CIN patients and controls, in either the vagina or cervix. The microbial community may be modulated by the onset of sexual activity, a known clinical risk factor for cervical neoplasia. Distinct patterns of perturbated bacteria were found in the vaginal and cervical microbiota, in which reduced Actinobacteria-related operational taxonomic units (OTUs) and increased Proteobacteria-related OTUs were found in the vagina and cervix, respectively. A good agreement between the direction of the top-significant perturbated OTUs was observed between the vaginal and cervical microbiome, suggesting a potential microbial migration in the reproductive tract. Enriched genera such as Sphingomonas and Stenotrophomonas were found in cervical microbiota-associated CIN. Multivariate analysis revealed Comamonas, Rhizobium, and Pseudomonas as independent genera contributing to CIN in the cervix. In summary, this study revealed the perturbation of microbiota in the presence of CIN and demonstrated a distinct pattern of characteristic bacteria community between the vagina and cervix involved in the development of CIN.

Trichomonas vaginalis infection is associated with increased risk of cervical carcinogenesis: A systematic review and meta‐analysis of 470 000 patients

“…The inadequate control of confounders may lead to an underestimation or overestimation of the analyzed associations. Third, it is not clear whether T. vaginalis infection causes the cervical environment to be more susceptible to HPV infection and to the subsequent CIN, or whether cervical dysplasia makes the environment more attractive to T. vaginalis infection 59 . Fourth, in the diagnosis of cervical lesions, some studies used cytology, which is subjective, and it is a diagnostic method that is difficult to replicate 60 .…”

“…Third, it is not clear whether T. vaginalis infection causes the cervical environment to be more susceptible to HPV infection and to the subsequent CIN, or whether cervical dysplasia makes the environment more attractive to T. vaginalis infection. 59 Fourth, in the diagnosis of cervical lesions, some studies used cytology, which is subjective, and it is a diagnostic method that is difficult to replicate. 60 Fifth, according to the GRADE assessment, the quality of evidence was low in six and very low in three outcomes.…”

Unraveling the Dysbiosis of Vaginal Microbiome to Understand Cervical Cancer Disease Etiology—An Explainable AI Approach

“…The prediction result of the model was interpreted using the SHAP algorithm. Increased Ralstonia impacted the prediction of the sample as cervical cancer with a higher probability (0.056) [ 50 ].…”

Changes in microbial composition and interaction patterns of female urogenital tract and rectum in response to HPV infection

“…Microbial migration and translocation between different parts of the reproductive tract have been proposed, and increasing infection is the main mode of transmission of pathogenic microorganisms in the female reproductive tract (71,72). In a study of reproductive tract microbes of women with CIN, it was found that the microorganisms with the most signi cant changes under the in uence of CIN, which had a good agreement between cervix and vagina (73). Firstly, signi cant associations between vaginal and urinary microbiomes were also demonstrated, with Lactobacillus being predominant in both urine and vagina (74).…”