Relationship between the Cervical Microbiome, HIV Status, and Precancerous Lesions
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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
Klein C, Gonzalez D, Samwel K, Kahesa C, Mwaiselage J, Aluthge N, Fernando S, West JT, Wood C, Angeletti PC
Journal
mBio
Year
2019
Keywords:
16S RNA, cervical cancer, deep sequencing, human immunodeficiency virus, human papillomavirus, microbiome
Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with high-grade squamous intraepithelial lesions (HSIL) (P = 0.13) than those without lesions. The most abundant OTUs associated with high-grade squamous intraepithelial lesions were Mycoplasmatales, Pseudomonadales, and Staphylococcus We suggest that a chronic mycoplasma infection of the cervix may contribute to HPV-dependent dysplasia by sustained inflammatory signals.IMPORTANCE HPV is known to be the causal agent in the majority of cervical cancers. However, the role of the cervical bacterial microbiome in cervical cancer is not clear. To investigate that possibility, we collected cervical cytobrush samples from 144 Tanzanian women and performed deep sequencing of bacterial 16S rRNA genes. We found that HIV-positive patients had greater bacterial richness (P = 0.01) than HIV-negative patients. We also observed that women with high-grade squamous intraepithelial lesions (HSIL) had greater cervical bacterial diversity than women with cytologically normal cervices. Data from our precise sampling of cervical lesions leads us to propose that Mycoplasma contributes to a cervical microbiome status that promotes HPV-related cervical lesions. These results suggest a greater influence of the bacterial microbiota on the outcome of HPV infection than previously thought.
Experiment 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Subjects
- Location of subjects
- United Republic of Tanzania
- 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
- negative for intraepithelial lesion or malignancy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- high-grade squamous intraepithelial lesions
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- high-grade squamous intraepithelial lesions (HSIL) comfirmed by Pap smear
- Group 0 sample size Number of subjects in the control (unexposed) group
- 23
- Group 1 sample size Number of subjects in the case (exposed) group
- 45
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)
- 0.1
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: figure 6a
Description: LEfSe linear discriminant analysis (LDA) scores between unmatched high-grade squamous intraepithelial lesions (HSIL) and negative for intraepithelial lesion (NILM)
Abundance in Group 1: increased abundance in high-grade squamous intraepithelial lesions
| NCBI | Quality Control | Links |
|---|---|---|
| Azotobacter group | ||
| Staphylococcus | ||
| Pseudomonadales | ||
| Mycoplasmatota | ||
| Mycoplasmatales | ||
| Staphylococcaceae |
Revision editor(s): WikiWorks
Signature 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: figure 6a
Description: LEfSe linear discriminant analysis (LDA) scores between unmatched high-grade squamous intraepithelial lesions (HSIL) and negative for intraepithelial lesion (NILM)
Abundance in Group 1: decreased abundance in high-grade squamous intraepithelial lesions
| NCBI | Quality Control | Links |
|---|---|---|
| Gammaproteobacteria | ||
| Finegoldia |
Revision editor(s): WikiWorks
Experiment 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Differences from previous experiment shown
Subjects
- Group 0 sample size Number of subjects in the control (unexposed) group
- 4
- Group 1 sample size Number of subjects in the case (exposed) group
- 4
Lab analysis
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- age
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: figure 6b
Description: LEfSe linear discriminant analysis (LDA) scores between matched high-grade squamous intraepithelial lesions (HSIL) and negative for intraepithelial lesion (NILM)
Abundance in Group 1: increased abundance in high-grade squamous intraepithelial lesions
| NCBI | Quality Control | Links |
|---|---|---|
| Streptococcus | ||
| Parvimonas | ||
| Mycoplasmatota | ||
| Mollicutes | ||
| Mycoplasmatales |
Revision editor(s): WikiWorks
Signature 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: figure 6b
Description: LEfSe linear discriminant analysis (LDA) scores between matched high-grade squamous intraepithelial lesions (HSIL) and negative for intraepithelial lesion (NILM)
Abundance in Group 1: decreased abundance in high-grade squamous intraepithelial lesions
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillaceae | ||
| Lactobacillus iners | ||
| Bacilli | ||
| Lactobacillales | ||
| Finegoldia |
Revision editor(s): WikiWorks
Experiment 3
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- HIV infection [X]Human immunodeficiency virus disease,[X]Human immunodeficiency virus disease (disorder),[X]Unspecified human immunodeficiency virus [HIV] disease,[X]Unspecified human immunodeficiency virus [HIV] disease (disorder),HIV - Human immunodeficiency virus infection,HIV INFECT,HIV Infection,HIV infection,HIV Infections,HIV infectious disease,HTLV III INFECT,HTLV III Infections,HTLV III LAV INFECT,HTLV III LAV Infections,HTLV WIII INFECTIONS,HTLV WIII LAV INFECTIONS,HTLV-III Infection,HTLV-III Infections,HTLV-III-LAV Infection,HTLV-III-LAV Infections,HUMAN IMMUNO VIRUS DIS,human immunodeficiency virus,Human immunodeficiency virus [HIV] disease,HUMAN IMMUNOdeficiency VIRUS [HIV] INFECTION,Human immunodeficiency virus caused disease or disorder,Human immunodeficiency virus disease,Human immunodeficiency virus disease (disorder),Human immunodeficiency virus disease or disorder,Human immunodeficiency virus infection,Human immunodeficiency virus infection (disorder),Human immunodeficiency virus infection, NOS,Human immunodeficiency virus infectious disease,human immunodeficiency virus infectious disease,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,LYMPHOTROPIC VIRUS TYPE III INFECTIONS HUMAN T,T LYMPHOTROPIC VIRUS TYPE III INFECT HUMAN,T Lymphotropic Virus Type III Infections, Human,T-Lymphotropic Virus Type III Infections, Human,Unspecified human immunodeficiency virus [HIV] disease (disorder),hIV infection
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- HIV-
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HIV+
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- HIV+ comfirmed by Standard Diagnostics HIV-1/2 3.0 detection kit
- Group 0 sample size Number of subjects in the control (unexposed) group
- 95
- Group 1 sample size Number of subjects in the case (exposed) group
- 39
Lab analysis
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- Not specified
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: figure 6c
Description: LEfSe linear discriminant analysis (LDA) scores.
Abundance in Group 1: increased abundance in HIV+
Signature 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: figure 6c
Description: LEfSe linear discriminant analysis (LDA) scores.
Abundance in Group 1: decreased abundance in HIV+
| NCBI | Quality Control | Links |
|---|---|---|
| Arcanobacterium | ||
| Ureaplasma | ||
| Limosilactobacillus reuteri | ||
| Actinomycetes | ||
| Bifidobacteriales | ||
| Bifidobacterium |
Revision editor(s): WikiWorks
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