Cervical Microbiota Associated with Higher Grade Cervical Intraepithelial Neoplasia in Women Infected with High-Risk Human Papillomaviruses
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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
Piyathilake CJ, Ollberding NJ, Kumar R, Macaluso M, Alvarez RD, Morrow CD
Journal
Cancer prevention research (Philadelphia, Pa.)
Year
2016
It is increasingly recognized that microbes that reside in and on human body sites play major roles in modifying the pathogenesis of several diseases, including cancer. However, specific microbes or microbial communities that can be mechanistically linked to cervical carcinogenesis remain largely unexplored. The purpose of the study was to examine the association between cervical microbiota and high-grade cervical intraepithelial neoplasia (CIN 2+) in women infected with high-risk (HR) human papillomaviruses (HPV) and to assess whether the cervical microbiota are associated with oxidative DNA damage as indicated by the presence of cervical cells positive for 8-hydroxy-2'-deoxyguanosine. The study included 340 women diagnosed with CIN 2+ (cases) and 90 diagnosed with CIN 1 (non-cases). Microbiota composition was determined by Illumina sequencing of the 16S rRNA gene amplified from DNA extracted from cervical mucus samples. Measures of alpha/beta-diversity were not associated with either CIN severity or oxidative DNA damage. However, a cervical mucosal community type (CT) dominated by L. iners and unclassified Lactobacillus spp was associated with CIN 2+ (OR = 3.48; 95% CI, 1.27-9.55). Sequence reads mapping to Lactobacillaceae, Lactobacillus, L. reuteri, and several sub-genus level Lactobacillus operational taxonomic units were also associated with CIN 2+ when examined independently (effect size >2.0; P < 0.05). Our 16S rRNA sequencing results need confirmation in independent studies using whole-genome shotgun sequencing and that would allow sharpening the suggested associations at finer taxonomic levels. Our results provide little evidence that DNA oxidative damage mediates the effect of the microbiome on the natural history of HPV infection and CIN severity. Cancer Prev Res; 9(5); 357-66. ©2016 AACR.
Experiment 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Subjects
- Location of subjects
- United States of America
- 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
- Cervical glandular intraepithelial neoplasia Cervical glandular intraepithelial neoplasia,cervical glandular intraepithelial neoplasia
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- CIN1
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- CIN2+
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patients with CIN2+ confirmed by colposcopy
- Group 0 sample size Number of subjects in the control (unexposed) group
- 90
- Group 1 sample size Number of subjects in the case (exposed) group
- 340
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)?
- Yes
- 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
- Chao1 Abundance-based estimator of species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Figure 2, supplemental table 1
Description: Differentially abundant taxa in CIN2+ group VS CIN1 group
Abundance in Group 1: increased abundance in CIN2+
Revision editor(s): WikiWorks, ChiomaBlessing
Signature 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Figure 2, supplemental table 1
Description: Differentially abundant taxa in CIN2+ group VS CIN1 group
Abundance in Group 1: decreased abundance in CIN2+
| NCBI | Quality Control | Links |
|---|---|---|
| Eubacteriales | ||
| Oscillospiraceae |
Revision editor(s): WikiWorks, ChiomaBlessing
Experiment 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- <=38.8% 8-OHdG-positive cervical cells
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- >38.8% 8-OHdG-positive cervical cells
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patients with >38.8% of 8-OHdG-positive cervical cells
- Group 0 sample size Number of subjects in the control (unexposed) group
- Not specified
- Group 1 sample size Number of subjects in the case (exposed) group
- Not specified
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
- unchanged
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Supplemental Figure 2
Description: Differentially abundant taxa in >38.8% 8-OHdG-positive cervical cells group VS <=38.8% 8-OHdG-positive cervical cells group
Abundance in Group 1: increased abundance in >38.8% 8-OHdG-positive cervical cells
| NCBI | Quality Control | Links |
|---|---|---|
| Agrobacterium | ||
| Azotobacter group | ||
| Betaproteobacteria | ||
| Burkholderiales | ||
| Comamonadaceae | ||
| Hyphomicrobiales | ||
| Limnohabitans | ||
| Oxalobacteraceae | ||
| Phenylobacterium | ||
| Pseudomonas | ||
| Rhizobiaceae |
Revision editor(s): WikiWorks, ChiomaBlessing
Signature 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Supplemental Figure 2
Description: Differentially abundant taxa in >38.8% 8-OHdG-positive cervical cells group VS <=38.8% 8-OHdG-positive cervical cells group
Abundance in Group 1: decreased abundance in >38.8% 8-OHdG-positive cervical cells
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridiaceae |
Revision editor(s): WikiWorks, ChiomaBlessing
Experiment 3
Reviewed Marked as Reviewed by Fatima on 2021/07/16
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- CIN1
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- CIN2+
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patients with CIN2+ confirmed by colposcopy
- Group 0 sample size Number of subjects in the control (unexposed) group
- 90
- Group 1 sample size Number of subjects in the case (exposed) group
- 340
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- raw counts
- Statistical test
- Negative Binomial Regression
- 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
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Supplemental Table 2
Description: Differentially abundant taxa in CIN2+ group VS CIN1 group
Abundance in Group 1: increased abundance in CIN2+
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia muciniphila | ||
| Limosilactobacillus reuteri |
Revision editor(s): WikiWorks, ChiomaBlessing
Signature 2
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Source: Supplemental Table 2
Description: Differentially abundant taxa in CIN2+ group VS CIN1 group
Abundance in Group 1: decreased abundance in CIN2+
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia muciniphila | ||
| Blautia producta | ||
| Clostridium perfringens | ||
| Collinsella aerofaciens | ||
| Prevotella melaninogenica | ||
| Segatella copri | ||
| Streptococcus agalactiae |
Revision editor(s): WikiWorks, ChiomaBlessing
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