Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity

Study information

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

26574055

DOI Digital object identifier for electronic documents.

10.1038/srep16865

URI

Authors

Mitra A, MacIntyre DA, Lee YS, Smith A, Marchesi JR, Lehne B, Bhatia R, Lyons D, Paraskevaidis E, Li JV, Holmes E, Nicholson JK, Bennett PR, Kyrgiou M

Journal

Scientific reports

Year

2015

Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n = 52), high-grade (HSIL; n = 92), invasive cervical cancer (ICC; n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10%; LSIL = 11/52,21%; HSIL = 25/92,27%; ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P < 0.01), Anaerococcus tetradius (P < 0.05) and Peptostreptococcus anaerobius (P < 0.05) and lower levels of Lactobacillus jensenii (P < 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota diversity and may be involved in regulating viral persistence and disease progression.

Experiment 1

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

Subjects

Location of subjects: United Kingdom

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Posterior fornix of vagina Pars posterior fornicis vaginae,Posterior fornix,Posterior part of fornix of vagina,Posterior fornix of vagina,posterior fornix of vagina

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Cervical glandular intraepithelial neoplasia Cervical glandular intraepithelial neoplasia,cervical glandular intraepithelial neoplasia

Group 0 name Corresponds to the control (unexposed) group for case-control studies: low grade squamus intraepithelial lesion

Group 1 name Corresponds to the case (exposed) group for case-control studies: high grade squamus intraepithelial lesion

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: high grade squamus intraepithelial lesion confirmed by histology or cytology

Group 0 sample size Number of subjects in the control (unexposed) group: 52

Group 1 sample size Number of subjects in the case (exposed) group: 92

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 14 days

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V2

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: unchanged

Richness Number of species: unchanged

Signature 1

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: figure 5

Description: Identification of vaginal microbiota biomarkers of LSIL vs. HSIL by LEfSe analysis

Abundance in Group 1: increased abundance in high grade squamus intraepithelial lesion

NCBI	Quality Control	Links
Peptostreptococcus anaerobius
Anaerococcus
Anaerococcus tetradius
Sneathia
Fusobacteriales
Sneathia sanguinegens
Fusobacteriota
Leptotrichiaceae

Revision editor(s): WikiWorks

Signature 2

Edit History Delete

Flag for review

Your review change was submitted

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: figure 5

Description: Identification of vaginal microbiota biomarkers of LSIL vs. HSIL by LEfSe analysis

Abundance in Group 1: decreased abundance in high grade squamus intraepithelial lesion

NCBI	Quality Control	Links
Lactobacillus jensenii
Limosilactobacillus coleohominis

Revision editor(s): WikiWorks