Cervicovaginal Fungi and Bacteria Associated With Cervical Intraepithelial Neoplasia and High-Risk Human Papillomavirus Infections in a Hispanic Population

From BugSigDB
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Godoy-Vitorino F, Romaguera J, Zhao C, Vargas-Robles D, Ortiz-Morales G, Vázquez-Sánchez F, Sanchez-Vázquez M, de la Garza-Casillas M, Martinez-Ferrer M, White JR, Bittinger K, Dominguez-Bello MG, Blaser MJ
Journal
Frontiers in microbiology
Year
2018
Keywords:
16S rRNA, ITS2, cervical cancer, cervicovaginal microbiota, fungi
The human cervicovaginal microbiota resides at an interface between the host and the environment and may affect susceptibility to disease. Puerto Rican women have high human papillomavirus (HPV) infection and cervical cancer rates. We hypothesized that the population structure of the cervicovaginal bacterial and fungal biota changed with cervical squamous intraepithelial lesions and HPV infections. DNA was extracted from cervix, introitus, and anal sites of 62 patients attending high-risk San Juan clinics. The 16S rRNA V4 region and ITS-2 fungal regions were amplified and sequenced using Illumina technology. HPV genotyping was determined by reverse hybridization with the HPV SPF10-LiPA25 kit. HPV prevalence was 84% of which ∼44% subjects were infected with high-risk HPV, ∼35% were co-infected with as many as 9 HPV types and ∼5% were infected with exclusively low-risk HPV types. HPV diversity did not change with cervical dysplasia. Cervical bacteria were more diverse in patients with CIN3 pre-cancerous lesions. We found enrichment of Atopobium vaginae and Gardnerella vaginalis in patients with CIN3 lesions. We found no significant bacterial biomarkers associated with HPV infections. Fungal diversity was significantly higher in cervical samples with high-risk HPV and introitus samples of patients with Atypical Squamous Cells of Undetermined Significance (ASCUS). Fungal biomarker signatures for vagina and cervix include Sporidiobolaceae and Sacharomyces for ASCUS, and Malassezia for high-risk HPV infections. Our combined data suggests that specific cervicovaginal bacterial and fungal populations are related to the host epithelial microenvironment, and could play roles in cervical dysplasia.

Experiment 1


Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

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
Vagina Vagina,vagina,Distal oviductal region,Distal portion of oviduct,Vaginae
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Cervical glandular intraepithelial neoplasia , Human papilloma virus infection Cervical glandular intraepithelial neoplasia,cervical glandular intraepithelial neoplasia,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
Atypical Squamous Cells of Undetermined Significance
Group 1 name Corresponds to the case (exposed) group for case-control studies
Low Grade Squamous Intraepithelial Lesion
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
low grade squamous intraepithelial lesion
Group 0 sample size Number of subjects in the control (unexposed) group
6
Group 1 sample size Number of subjects in the case (exposed) group
18
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
2 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
-V2
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
Mann-Whitney (Wilcoxon)
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

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, ChiomaBlessing

Source: Figure 8

Description: Fungal biomarker signatures in Low Grade Squamous Intraepithelial Lesion compared to Atypical Squamous Cells of Undetermined Significance (in the 58 introitus samples)

Abundance in Group 1: decreased abundance in Low Grade Squamous Intraepithelial Lesion

NCBI Quality ControlLinks
Saccharomyces
Sporidiobolaceae

Revision editor(s): WikiWorks, ChiomaBlessing

Experiment 2


Reviewed Marked as Reviewed by Fatima on 2021/04/20

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Low risk-HPV
Group 1 name Corresponds to the case (exposed) group for case-control studies
High risk-HPV
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
High risk-HPV
Group 0 sample size Number of subjects in the control (unexposed) group
3
Group 1 sample size Number of subjects in the case (exposed) group
27

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Fatima on 2021/04/20

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, ChiomaBlessing

Source: Figure 8

Description: Fungal biomarker signatures in high risk-HPV group compared to low risk-HPV group (in the 58 introitus samples)

Abundance in Group 1: increased abundance in High risk-HPV

NCBI Quality ControlLinks
Malassezia

Revision editor(s): WikiWorks, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Fatima on 2021/04/20

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, ChiomaBlessing

Source: Figure 8

Description: Fungal biomarker signatures in high risk-HPV group compared to low risk-HPV group (in the 58 introitus samples)

Abundance in Group 1: decreased abundance in High risk-HPV

NCBI Quality ControlLinks
Sporidiobolaceae

Revision editor(s): WikiWorks, ChiomaBlessing

Experiment 3


Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): ChiomaBlessing, WikiWorks

Differences from previous experiment shown

Subjects

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
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Atypical Squamous Cells of Undetermined Significance
Group 1 name Corresponds to the case (exposed) group for case-control studies
Low Grade Squamous Intraepithelial Lesion
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
low grade squamus intraepithelial lesion
Group 0 sample size Number of subjects in the control (unexposed) group
6
Group 1 sample size Number of subjects in the case (exposed) group
18

Lab analysis

Statistical Analysis

Alpha Diversity

Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): ChiomaBlessing, WikiWorks

Source: Figure 8

Description: Fungal biomarker signatures in Low Grade Squamous Intraepithelial Lesion compared to Atypical Squamous Cells of Undetermined Significance (in the 55 cervical samples)

Abundance in Group 1: decreased abundance in Low Grade Squamous Intraepithelial Lesion

NCBI Quality ControlLinks
Sporidiobolaceae

Revision editor(s): ChiomaBlessing, WikiWorks

Experiment 4


Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Low risk-HPV
Group 1 name Corresponds to the case (exposed) group for case-control studies
High risk-HPV
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
High risk-HPV
Group 0 sample size Number of subjects in the control (unexposed) group
3
Group 1 sample size Number of subjects in the case (exposed) group
27

Lab analysis

Statistical Analysis

Alpha Diversity

Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, ChiomaBlessing

Source: Figure 8

Description: Fungal biomarker signatures in Low Grade Squamous Intraepithelial Lesion compared to Atypical Squamous Cells of Undetermined Significance (in 55 cervical samples)

Abundance in Group 1: increased abundance in High risk-HPV

NCBI Quality ControlLinks
Malassezia

Revision editor(s): WikiWorks, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, ChiomaBlessing

Source: Figure 8

Description: Fungal biomarker signatures in Low Grade Squamous Intraepithelial Lesion compared to Atypical Squamous Cells of Undetermined Significance (in 55 cervical samples)

Abundance in Group 1: decreased abundance in High risk-HPV

NCBI Quality ControlLinks
Sporidiobolaceae

Revision editor(s): WikiWorks, ChiomaBlessing