Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort

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Reviewed Marked as Reviewed by Atrayees on 2023-6-28
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Chen Y, Qiu X, Wang W, Li D, Wu A, Hong Z, Di W, Qiu L
Journal
BMC infectious diseases
Year
2020
Keywords:
Cervical cancer, Cervical intraepithelial neoplasia, Human papillomavirus, Vaginal microbiome
BACKGROUND: In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts. METHODS: The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n = 78), women with low-grade squamous intraepithelial lesions (LSIL, n = 51), women with high-grade squamous intraepithelial lesions (HSIL, n = 23), women with invasive cervical cancer (Cancer, n = 9) and healthy women without HPV infection (Normal, n = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. RESULTS: HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs. CONCLUSIONS: This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks, Atrayees

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled (if applicable)
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
human papilloma virus infection HPV,Human Papilloma Virus Infection,Human papilloma Virus infection,human papilloma virus infection,Human papillomavirus caused disease or disorder,Human papillomavirus disease or disorder,Human Papillomavirus Infection,Human Papillomavirus infection,Human papillomavirus infectious disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy control
Group 1 name Corresponds to the case (exposed) group for case-control studies
HPV +
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
HPV-infected women without CIN confirmed by HPV genotyping test and examination
Group 0 sample size Number of subjects in the control (unexposed) group
68
Group 1 sample size Number of subjects in the case (exposed) group
78
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
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

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
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
4

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Richness Number of species
increased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
increased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson

Source: Figure 5

Description: The unique taxa and microbiomarkers for different groups

Abundance in Group 1: increased abundance in HPV +

NCBI Quality ControlLinks
Megasphaera

Revision editor(s): Cynthia Anderson

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson

Source: Figure 5

Description: The unique taxa and microbiomarkers for different groups

Abundance in Group 1: decreased abundance in HPV +

NCBI Quality ControlLinks
Atopobium
Bacilli
Coriobacteriaceae
Coriobacteriales
Bacillota
Lactobacillaceae
Lactobacillales
Lactobacillus
Fannyhessea vaginae

Revision editor(s): Cynthia Anderson

Experiment 2


Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
cervical glandular intraepithelial neoplasia cervical glandular intraepithelial neoplasia
Group 1 name Corresponds to the case (exposed) group for case-control studies
LSIL
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
women with low-grade squamous intraepithelial lesions confirmed by biopsy
Group 0 sample size Number of subjects in the control (unexposed) group
78
Group 1 sample size Number of subjects in the case (exposed) group
51

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson

Source: Figure 5

Description: The unique taxa and microbiomarkers for different groups

Abundance in Group 1: increased abundance in LSIL

NCBI Quality ControlLinks
Prevotella amnii

Revision editor(s): Cynthia Anderson

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson

Source: Figure 5

Description: The unique taxa and microbiomarkers for different groups.

Abundance in Group 1: decreased abundance in LSIL

NCBI Quality ControlLinks
Atopobium
Bacilli
Coriobacteriaceae
Coriobacteriales
Bacillota
Lactobacillaceae
Lactobacillales
Lactobacillus
Fannyhessea vaginae

Revision editor(s): Cynthia Anderson

Experiment 3


Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
HSIL
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
women with high-grade squamous intraepithelial lesions confirmed by biopsy
Group 0 sample size Number of subjects in the control (unexposed) group
68
Group 1 sample size Number of subjects in the case (exposed) group
23

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson

Source: Figure 5

Description: The unique taxa and microbiomarkers for different groups

Abundance in Group 1: increased abundance in HSIL

NCBI Quality ControlLinks
Prevotella
Clostridia
Eubacteriales
Prevotellaceae
Lachnospiraceae
Shuttleworthia
Streptococcaceae
Hoylesella timonensis

Revision editor(s): Cynthia Anderson

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson

Source: Figure 5

Description: The unique taxa and microbiomarkers for different groups

Abundance in Group 1: decreased abundance in HSIL

NCBI Quality ControlLinks
Atopobium
Bacilli
Coriobacteriaceae
Coriobacteriales
Bacillota
Lactobacillaceae
Lactobacillales
Lactobacillus
Fannyhessea vaginae

Revision editor(s): Cynthia Anderson

Experiment 4


Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
cervical cancer cancer of uterine cervix,cervical neoplasm,cervix cancer,cervix uteri cancer,malignant cervical neoplasm,malignant cervical tumor,malignant cervix neoplasm,malignant cervix tumor,malignant cervix uteri neoplasm,malignant cervix uteri tumor,malignant neoplasm of cervix,malignant neoplasm of cervix uteri,malignant neoplasm of the cervix,malignant neoplasm of the cervix uteri,malignant neoplasm of the uterine cervix,malignant neoplasm of uterine cervix,malignant tumor of cervix,malignant tumor of cervix uteri,malignant tumor of the cervix,malignant tumor of the cervix uteri,malignant tumor of the uterine cervix,malignant tumor of uterine cervix,malignant uterine cervix neoplasm,malignant uterine cervix tumor,tumor of the cervix uteri,uterine cervical neoplasm,uterine cervix cancer,cervical cancer
Group 1 name Corresponds to the case (exposed) group for case-control studies
cervical cancer
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
women with cervical cancer confirmed by biopsy
Group 1 sample size Number of subjects in the case (exposed) group
9

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson

Source: Figure 5

Description: The unique taxa and microbiomarkers for different groups

Abundance in Group 1: increased abundance in cervical cancer

NCBI Quality ControlLinks
Bacillales
Fusobacteriales
Fusobacteriia
Fusobacteriota
Bacillaceae
Pseudomonadota
Bacillus
Bacteroidia
Bacteroidales
Bacteroidota
Betaproteobacteria
Sneathia
Leptotrichiaceae
Comamonadaceae
Burkholderiales
Acidovorax
Fusobacterium
Fusobacteriaceae
Oceanobacillus
Oceanobacillus profundus
Porphyromonadaceae
Porphyromonas
Veillonellaceae
Negativicutes
Selenomonadales
Eubacteriales
Anaerococcus
Porphyromonas uenonis

Revision editor(s): Cynthia Anderson

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2021/03/20

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson

Source: Figure 5

Description: The unique taxa and microbiomarkers for different groups

Abundance in Group 1: decreased abundance in cervical cancer

NCBI Quality ControlLinks
Atopobium
Bacilli
Coriobacteriaceae
Coriobacteriales
Bacillota
Lactobacillaceae
Lactobacillales
Lactobacillus
Fannyhessea vaginae

Revision editor(s): Cynthia Anderson

Experiment 5


Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2023/06/28

Curator: Atrayees

Revision editor(s): Atrayees

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
human papilloma virus infection HPV,Human Papilloma Virus Infection,Human papilloma Virus infection,human papilloma virus infection,Human papillomavirus caused disease or disorder,Human papillomavirus disease or disorder,Human Papillomavirus Infection,Human Papillomavirus infection,Human papillomavirus infectious disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy control
Group 1 name Corresponds to the case (exposed) group for case-control studies
HPV+
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
HPV-infected women without CIN confirmed by HPV genotyping test and examination
Group 1 sample size Number of subjects in the case (exposed) group
78

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Mann-Whitney (Wilcoxon)
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Not specified
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Richness Number of species
increased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
increased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2023/06/28

Curator: Atrayees

Revision editor(s): Atrayees

Source: Fig 3, 4

Description: Relative abundance of taxa across the samples

Abundance in Group 1: increased abundance in HPV+

NCBI Quality ControlLinks
Bacteroidota
Fusobacteriia
Pseudomonadota
Prevotella
Bacillus
Sneathia
Megasphaera
Streptococcus
Anaerococcus

Revision editor(s): Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-28

Curated date: 2023/06/28

Curator: Atrayees

Revision editor(s): Atrayees

Source: Figure 3, 4

Description: Relative abundance of taxa across the samples

Abundance in Group 1: decreased abundance in HPV+

NCBI Quality ControlLinks
Bacillota
Atopobium

Revision editor(s): Atrayees