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

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Yang Q, Wang Y, Wei X, Zhu J, Wang X, Xie X, Lu W
Frontiers in cellular and infection microbiology
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

Needs review

Curated date: 2021/03/21

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks


Location of subjects
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
Cervicovaginal secretion, Posterior fornix of vagina Cervicovaginal secretion,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
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with HPV-16 confirmed by HPV genotyping assay
Group 0 sample size Number of subjects in the control (unexposed) group
Group 1 sample size Number of subjects in the case (exposed) group
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
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Statistical Analysis

Statistical test
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool