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Changes of vaginal microbiota during cervical carcinogenesis in women with human papillomavirus infection.

ABSTRACT: OBJECTIVE:To evaluate the changes of vaginal microbiota during cervical carcinogenesis in women with high-risk human papillomavirus infection. MATERIALS AND METHODS:Vaginal microbiota was analyzed using next-generation sequencing in women with normal, cervical intraepithelial neoplasia (CIN), or cervical cancer. RESULTS:A marked decrease of Lactobacillus crispatus was found in the CIN/cancer groups compared with that in the normal group. The diversity of microorganisms increased in patients with CIN or cervical cancer with HPV infection. Atopobium vaginae (OR 4.33, 95% CI 1.15-16.32), Dialister invisus (OR 4.89, 95% CI 1.20-19.94), Finegoldia magna (OR 6.00, 95% CI 1.08-33.27), Gardnerella vaginalis (OR 7.43, 95% CI 1.78-31.04), Prevotella buccalis (OR 11.00, 95% CI 2.00-60.57), and Prevotella timonensis (OR 6.00, 95% CI 1.46-24.69) were significantly associated with the risk of CIN 2/3 or cervical cancer. CONCLUSION:Women with the CIN and cervical cancer showed a high diversity in vaginal microbiota. Depletion of Lactobacillus crispatus and increased abundance of anaerobic bacteria were detected in women with cervical disease.

SUBMITTER: So KA

PROVIDER: S-EPMC7498004 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Changes of vaginal microbiota during cervical carcinogenesis in women with human papillomavirus infection.

So Kyeong A KA Yang Eun Jung EJ Kim Nae Ry NR Hong Sung Ran SR Lee Jae-Ho JH Hwang Chang-Sun CS Shim Seung-Hyuk SH Lee Sun Joo SJ Kim Tae Jin TJ

PloS one 20200917 9

<h4>Objective</h4>To evaluate the changes of vaginal microbiota during cervical carcinogenesis in women with high-risk human papillomavirus infection.<h4>Materials and methods</h4>Vaginal microbiota was analyzed using next-generation sequencing in women with normal, cervical intraepithelial neoplasia (CIN), or cervical cancer.<h4>Results</h4>A marked decrease of Lactobacillus crispatus was found in the CIN/cancer groups compared with that in the normal group. The diversity of microorganisms incr ...[more]

PMID: 32941440

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Project description:The cervical microbiota is essential in female sexual health, and its altered states seem to have a central role in the dynamic of high-risk papillomavirus (hrHPV) infections. This study aimed to evaluate the variation in bacterial communities' compositions according to hrHPV. We collected two samples per woman, with a difference of 12 ± 1 months between them, and performed a follow-up on 66 of these women. The viral load (VL) of the hrHPV was estimated by quantitative PCR (qPCR), then it was normalized (using the HMBS gene as reference) and transformed to the Log10 scale to facilitate the interpretation. The VL was categorized as Negative, without hrHPV copies; Low, less than 100 hrHPV copies; Medium, between 100 to 102 hrHPV copies; and High, >102 hrHPV copies. The microbiota composition was described through the Illumina Novaseq PE250 platform. The diversity analyses revealed changes regarding the hrHPV VL, where women with low VL (<100 hrHPV copies) presented high diversity. The community state type (CST) IV was the most common. However, in women with high VL, a lower association with Lactobacillus depletion was found. Lactobacillus gallinarum and L. iners were the most abundant species in women with high VL, whereas women with low VL had a 6.06 greater probability of exhibiting Lactobacillus dominance. We identified conspicuous differences in the abundance of 78 bacterial genera between women with low and high VL, where 26 were depleted (e.g., Gardnerella) and 52 increased (e.g., Mycoplasma). A multilevel mixed-effects linear regression showed changes in the diversity due to the interaction between the measurement time and the VL, with a decrease in diversity in the second follow-up in women with low VL (Coeff. = 0.47), whereas the women with medium VL displayed an increase in diversity (Coeff. = 0.58). Here, we report for the first time that the cervical microbiota is influenced by the number of copies of hrHPV, where a decrease in the abundance of Lactobacillus, greater diversity, and enrichment of bacterial taxa is relevant in women with low VL.

Project description:BackgroundThe female genital tract is an important bacterial habitat of the human body, and vaginal microbiota plays a crucial role in vaginal health. The alteration of vaginal microbiota affects millions of women annually, and is associated with numerous adverse health outcomes, including human papillomavirus (HPV) infection. However, previous studies have primarily focused on the association between bacterial vaginosis and HPV infection. Little is known about the composition of vaginal microbial communities involved in HPV acquisition. The present study was performed to investigate whether HPV infection was associated with the diversity and composition of vaginal microbiota.MethodsA total of 70 healthy women (32 HPV-negative and 38 HPV-positive) with normal cervical cytology were enrolled in this study. Culture-independent polymerase chain reaction-denaturing gradient gel electrophoresis was used to measure the diversity and composition of vaginal microbiota of all subjects.ResultsWe found significantly greater biological diversity in the vaginal microbiota of HPV-positive women (p < 0.001). Lactobacillus, including L. gallinarum, L. iners and L. gasseri, was the predominant genus and was detected in all women. No significant difference between HPV-positive and HPV-negative women was found for the frequency of detection of L. gallinarum (p = 0.775) or L. iners (p = 0.717), but L. gasseri was found at a significantly higher frequency in HPV-positive women (p = 0.005). Gardnerella vaginalis was also found at a significantly higher frequency in HPV-positive women (p = 0.031). Dendrograms revealed that vaginal microbiota from the two groups had different profiles.ConclusionsOur study is the first systematic evaluation of an association between vaginal microbiota and HPV infection, and we have demonstrated that compared with HPV-negative women, the bacterial diversity of HPV-positive women is more complex and the composition of vaginal microbiota is different.

Project description:BackgroundHuman papillomavirus (HPV) infection is the leading cause of cervical cancer. More and more studies discovered that cervical microbiota (CM) composition correlated with HPV infection and the development of cervical cancer. However, more studies need to be implemented to clarify the complex interaction between microbiota and the mechanism of disease development, especially in a specific area of China.Materials and methodsIn this study, 16S rDNA sequencing was applied on 276 Thin-prep Cytologic Test (TCT) samples of patients from the Sanmenxia area. Systematical analysis of the microbiota structure, diversity, group, and functional differences between different HPV infection groups and age groups, and co-occurrence relationships of the microbiota was carried out.ResultsThe major microbiota compositions of all patients include Lactobacillus iners, Escherichia coli, Enterococcus faecalis, and Atopobium vaginae at species level, and Staphylococcus, Lactobacillus, Gardnerella, Bosea, Streptococcus, and Sneathia in genus level. Microbiota diversity was found significantly different between HPV-positive (Chao1 index: 98.8869, p < 0.01), unique-268 infected (infections with one of the HPV genotype 52, 56, or 58, 107.3885, p < 0.01), multi-268 infected (infections with two or more of HPV genotype 52, 56, and 58, 97.5337, p = 0.1012), other1 (94.9619, p < 0.05) groups and HPV-negative group (83.5299). Women older than 60 years old have higher microbiota diversity (108.8851, p < 0.01, n = 255) than younger women (87.0171, n = 21). The abundance of Gardnerella and Atopobium vaginae was significantly higher in the HPV-positive group than in the HPV-negative group, while Burkholderiaceae and Mycoplasma were more abundant in the unique-268 group compared to the negative group. Gamma-proteobacteria and Pseudomonas were found more abundant in older than 60 patients than younger groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) analysis revealed the effects on metabolism by microbiota that the metabolism of cells, proteins, and genetic information-related pathways significantly differed between HPV-negative and positive groups. In contrast, lipid metabolism, signal transduction, and cell cycle metabolism pathway significantly differed between multi-268 and negative groups.ConclusionThe HPV infection status and age of women were related to CM's diversity and function pathways. The complex CM co-occurrent relationships and their mechanism in disease development need to be further investigated.

Dataset Information

Changes of vaginal microbiota during cervical carcinogenesis in women with human papillomavirus infection.

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Changes of vaginal microbiota during cervical carcinogenesis in women with human papillomavirus infection.

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