The Alterations of Vaginal Microbiome in HPV16 Infection as Identified by Shotgun Metagenomic Sequencing

Study information

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-25

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

32656096

DOI Digital object identifier for electronic documents.

10.3389/fcimb.2020.00286

URI

Authors

Yang Q, Wang Y, Wei X, Zhu J, Wang X, Xie X, Lu W

Journal

Frontiers in cellular and infection microbiology

Year

2020

Keywords:

HPV infection, cervical cancer, metabolism, shotgun metagenomic sequencing, vaginal microbiome

The association of microbiome imbalance with cancer development is being one of the research hotspots. Persistent HPV infection is a causal event in cervical cancer initiation, but, little is known about the microbiome composition and function in HPV infection. Here we identified the compositional and functional alterations on vaginal samples from 27 HPV16 positive women and 25 age-matched HPV negative controls using shotgun metagenomic sequencing, to provide a comprehensive investigation describing the microbial abundances and enriched metabolic functions in cervicovaginal metagenomes. We further employed qPCR assays to evaluate two selected gene markers of HPV16 infection in an independent validation cohort consisting of 88 HPV16 positive women and 81 controls, and six selected species markers in a subset of validation cohort of 45 HPV16 positive women and 53 controls. We found that the relative abundance of dominant Firmicutes was lower, Actinobacteria, Fusobacteria and viruses phyla were significantly higher in the HPV16-positive group; 77 genera including Gardnerella, Peptostreptococcus, and Prevotella were higher, and 20 genera including Lactobacillus and Aerococcus were lower in the HPV16-positive women. Abundance of 12 genes, 17 genera, and 7 species biomarkers showed an excellent predictive power for the HPV16-positive individuals, with 0.861, 0.819, and 0.918, respectively, of the area under the receiver-operating characteristic curve (AUC). We further characterized the microbial function, and revealed that HPV16-positive women were enriched in metabolism and membrane transport, and depleted by glycan biosynthesis and metabolism, and replication and repair. Quantitative PCR measurements validated that one gene marker and three species were significantly enriched in HPV16-positive women. These results highlight a fundamental fact that there are altered composition and function of the vaginal microbiome in HPV16-positive women, suggesting that vaginal dysbiosis may be associated with HPV infection in the female genital tract.

Experiment 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-1-25

Curated date: 2021/03/21

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks, Peace Sandy

Subjects

Location of subjects: China

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: Vaginal fluid

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

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-16+

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with HPV-16 positive without lesion confirmed by HPV genotyping assay

Group 0 sample size Number of subjects in the control (unexposed) group: 25

Group 1 sample size Number of subjects in the case (exposed) group: 27

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 1 month

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

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

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

Matched on Factors on which subjects have been matched on in a case-control study: age

Alpha Diversity

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

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

Signature 1

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Curated date: 2021/03/21

Curator: Cynthia Anderson

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Source: Figure 3(B)

Description: Vaginal microbiome as HPV16-infection markers. (B) Histogram of the LDA scores computed for species differentially abundant between HPV16-positive women and controls. The LDA scores (log10) > 2 are listed

Abundance in Group 1: increased abundance in HPV-16+

NCBI	Quality Control	Links
Anaerococcus tetradius
Atopobium deltae
Chlamydia trachomatis
Dialister invisus
Dialister micraerophilus
Fusobacterium nucleatum
Gardnerella vaginalis
Gemelliphila asaccharolytica
Kytococcus sedentarius
Mageeibacillus indolicus
Mobiluncus curtisii
Nocardia brevicatena
Olsenella uli
Paracoccus denitrificans
Parvimonas micra
Pedobacter panaciterrae
Peptoniphilus harei
Peptoniphilus lacrimalis
Peptostreptococcus anaerobius
Prevotella amnii
Prevotella bivia
Prevotella corporis
Prevotella disiens
Prevotella melaninogenica
Schaalia turicensis
Solobacterium moorei
Streptomyces auratus
Stutzerimonas stutzeri
Veillonella montpellierensis
Methanobrevibacter oralis
Enterocytozoon bieneusi
Melampsora laricis-populina
Saccharomyces boulardii (nom. inval.)
Kalmanozyma brasiliensis
Malassezia restricta
Candida albicans
Saccharomyces mikatae
Pseudogymnoascus
Saccharomyces cerevisiae
Saccharomyces kudriavzevii
Enterobacteriaceae
Lactobacillus
Alphapapillomavirus 14

Revision editor(s): Cynthia Anderson, Peace Sandy, WikiWorks

Signature 2

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Curated date: 2024/01/25

Curator: Peace Sandy

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Source: Figure 3 (B)

Description: Vaginal microbiome as HPV16-infection markers. (B) Histogram of the LDA scores computed for species differentially abundant between HPV16-positive women and controls. The LDA scores (log10) > 2 are listed

Abundance in Group 1: decreased abundance in HPV-16+

NCBI	Quality Control	Links
Enterococcus sp. 1140_ESPC
Alphapapillomavirus
Mitosporidium daphniae
Nakaseomyces glabratus
Mucor ambiguus
Nosema bombycis

Revision editor(s): Peace Sandy, WikiWorks