Cervicovaginal microbiome and natural history of HPV in a longitudinal study
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Usyk M, Zolnik CP, Castle PE, Porras C, Herrero R, Gradissimo A, Gonzalez P, Safaeian M, Schiffman M, Burk RD
Journal
PLoS pathogens
Year
2020
BACKGROUND: Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections. However, only a small percentage of high-risk (HR) HPV infections progress to cervical precancer and cancer. In this study, we investigated the role of the cervicovaginal microbiome (CVM) in the natural history of HR-HPV. METHODS: This study was nested within the placebo arm of the Costa Rica HPV Vaccine Trial that included women aged 18-25 years of age. Cervical samples from two visits of women with an incident HR-HPV infection (n = 273 women) were used to evaluate the prospective role of the CVM on the natural history of HR-HPV. We focus specifically on infection clearance, persistence, and progression to cervical intraepithelial neoplasia grade 2 and 3 (CIN2+). The CVM was characterized by amplification and sequencing the bacterial 16S V4 rRNA gene region and the fungal ITS1 region using an Illumina MiSeq platform. OTU clustering was performed using QIIME2. Functional groups were imputed using PICRUSt and statistical analyses were performed using R. RESULTS: At Visit 1 (V1) abundance of Lactobacillus iners was associated with clearance of incident HR-HPV infections (Linear Discriminant Analysis (LDA)>4.0), whereas V1 Gardnerella was the dominant biomarker for HR-HPV progression (LDA>4.0). At visit 2 (V2), increased microbial Shannon diversity was significantly associated with progression to CIN2+ (p = 0.027). Multivariate mediation analysis revealed that the positive association of V1 Gardnerella with CIN2+ progression was due to the increased cervicovaginal diversity at V2 (p = 0.040). A full multivariate model of key components of the CVM showed significant protective effects via V1 genus Lactobacillus, OR = 0.41 (0.22-0.79), V1 fungal diversity, OR = 0.90 (0.82-1.00) and V1 functional Cell Motility pathway, OR = 0.75 (0.62-0.92), whereas V2 bacterial diversity, OR = 1.19 (1.03-1.38) was shown to be predictive of progression to CIN2+. CONCLUSION: This study demonstrates that features of the cervicovaginal microbiome are associated with HR-HPV progression in a prospective longitudinal cohort. The analyses indicated that the association of Gardnerella and progression to CIN2+ may actually be mediated by subsequent elevation of microbial diversity. Identified features of the microbiome associated with HR-HPV progression may be targets for therapeutic manipulation to prevent CIN2+. TRIAL REGISTRATION: ClinicalTrials.gov NCT00128661.
Experiment 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Subjects
- Location of subjects
- Costa Rica
- 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
- Uterine cervix Canalis cervicis uteri,Caudal segment of uterus,Cervical canal,Cervical canal of uterus,Cervix,Cervix of uterus,Cervix uteri,Neck of uterus,Uterine cervix,uterine cervix
- 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,Human papilloma virus infection
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- HPV (clearance)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Visit 1 HPV (progression)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- HPV progression to CIN2+ lesion diagnosis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 70
- Group 1 sample size Number of subjects in the case (exposed) group
- 33
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V4
- 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)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Figure 4
Description: Bacteria associated with progression to CIN2+ identified using LEfSe
Abundance in Group 1: increased abundance in Visit 1 HPV (progression)
Signature 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Figure 4
Description: Bacteria associated with progression to CIN2+ identified using LEfSe
Abundance in Group 1: decreased abundance in Visit 1 HPV (progression)
| NCBI | Quality Control | Links |
|---|---|---|
| Segatella paludivivens | ||
| Lactobacillus iners |
Revision editor(s): WikiWorks
Experiment 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Visit 2 HPV (progression)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 69
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Figure 4
Description: Bacteria associated with progression to CIN2+ identified using LEfSe
Abundance in Group 1: increased abundance in Visit 2 HPV (progression)
Revision editor(s): WikiWorks
Signature 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Figure 4
Description: Bacteria associated with progression to CIN2+ identified using LEfSe
Abundance in Group 1: decreased abundance in Visit 2 HPV (progression)
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomyces johnsonii | ||
| Atopobium minutum | ||
| Acetivibrio clariflavus |
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