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

Study information

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

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

30405584

DOI Digital object identifier for electronic documents.

10.3389/fmicb.2018.02533

URI Uniform resource identifier for web resources.

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

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

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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects: United States of America

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: Vagina Distal oviductal region,Distal portion of oviduct,Vaginae,Vagina

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: cervical glandular intraepithelial neoplasia , human papilloma virus infection 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

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

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

Experiment 2

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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects: United States of America

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: Vagina Distal oviductal region,Distal portion of oviduct,Vaginae,Vagina

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: cervical glandular intraepithelial neoplasia , human papilloma virus infection 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

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
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

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

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: increased
Richness Number of species: unchanged

Experiment 3

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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects: United States of America

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: 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

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: cervical glandular intraepithelial neoplasia , human papilloma virus infection 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

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
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

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

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

Richness Number of species: unchanged

Experiment 4

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Flag for review

Your review change was submittedDuplicate this Experiment Add a new Signature

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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects: United States of America

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: 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

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: cervical glandular intraepithelial neoplasia , human papilloma virus infection 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

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
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

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

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

Richness Number of species: unchanged