Association of cervical microbial community with persistence, clearance and negativity of Human Papillomavirus in Korean women: a longitudinal study

Study information

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

30341386

DOI Digital object identifier for electronic documents.

10.1038/s41598-018-33750-y

URI Uniform resource identifier for web resources.

Authors

Arokiyaraj S, Seo SS, Kwon M, Lee JK, Kim MK

Journal

Scientific reports

Year

2018

The present study aimed to identify the cervical microbes that are associated with HPV negativity, HPV clearance and HPV persistence and to assess the microbes' longitudinal associations as related to HPV infection dynamics among Korean women. We enrolled 41 women with 107 samples, and classified them according to the HPV infection dynamics: HPV negativity (21 samples, 10 subjects), HPV clearance (42 samples, 15 subjects), and HPV persistence (44 samples, 16 subjects). Cervical swabs were collected at the baseline and six-month-interval follow-up visits. HPV positivity was determined by HPV DNA HC2 assay, and the microbiome was analyzed using 16SrRNA pyrosequencing, linear discriminant analysis effect size and multivariate logistic analysis. In the multivariate logistic analysis results, Lactobacillus crispatus (multivariate OR (mOR) = 8.25, 95% CI 2.13~32.0) was predominant in the HPV-negative group. We observed that Eubacterium eligens (mOR = 11.5, 95% CI 1.31~101.4), Gardnerella vaginalis (mOR = 17.0, 95% CI 2.18-131.8), and Ureaplasma urealyticum (mOR = 7.42, 95% CI 1.3-42.46) had the strongest associations with HPV clearance, and Lactobacillus johnsonii (mOR = 16.4, 95% CI 1.77-152.2) with HPV persistence. Overall, greater diversity was observed in HPV-persistence than in HPV-negative women. Our findings suggest that the presence and prevalence of a specific cervical microbiome are factors involved in HPV dynamics.

Experiment 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects: South Korea

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: Uterus Uterus

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

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: HPV persistent
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: HPV DNA was detected using the Digene HC2 high-risk DNA test (Qiagen, Gaithersburg, MD, USA) with signal amplification and chemiluminescence for 13 types of HR-HPV scored in RLU/PC. A positive result indicated a concentration of 1 pg/ml or higher than the RLU/cutoff ratio (RLU of the specimen/mean RLU of 2 positive controls).
Group 0 sample size Number of subjects in the control (unexposed) group: 15
Group 1 sample size Number of subjects in the case (exposed) group: 16

Lab analysis

Sequencing type: 16S

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Roche454

Statistical Analysis

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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, menopause, contraception, smoking behavior

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

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Phyu Han

Revision editor(s): WikiWorks

Source: Table 2

Description: Mulivariate odd ratios of species according to different types of HPV

Abundance in Group 1: increased abundance in HPV persistent

NCBI	Links
Parabacteroides johnsonii

Revision editor(s): WikiWorks

Experiment 2

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects: South Korea

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: Uterus Uterus

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

Group 0 name Corresponds to the control (unexposed) group for case-control studies: HPV negative
Group 1 name Corresponds to the case (exposed) group for case-control studies: HPV clearance
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: HPV DNA was detected using the Digene HC2 high-risk DNA test (Qiagen, Gaithersburg, MD, USA) with signal amplification and chemiluminescence for 13 types of HR-HPV scored in RLU/PC. A positive result indicated a concentration of 1 pg/ml or higher than the RLU/cutoff ratio (RLU of the specimen/mean RLU of 2 positive controls).
Group 0 sample size Number of subjects in the control (unexposed) group: 10
Group 1 sample size Number of subjects in the case (exposed) group: 15

Lab analysis

Sequencing type: 16S

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Roche454

Statistical Analysis

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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, menopause, contraception, smoking behavior

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

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Phyu Han

Revision editor(s): WikiWorks

Source: Table 2

Description: Mulivariate odd ratios of species according to different types of HPV

Abundance in Group 1: increased abundance in HPV clearance

NCBI	Links
Gardnerella vaginalis ⚠
Ureaplasma urealyticum

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Experiment 3

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects: South Korea

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: Uterus Uterus

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

Group 0 name Corresponds to the control (unexposed) group for case-control studies: HPV presistent and clearance
Group 1 name Corresponds to the case (exposed) group for case-control studies: HPV negative
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: HPV DNA was detected using the Digene HC2 high-risk DNA test (Qiagen, Gaithersburg, MD, USA) with signal amplification and chemiluminescence for 13 types of HR-HPV scored in RLU/PC. A positive result indicated a concentration of 1 pg/ml or higher than the RLU/cutoff ratio (RLU of the specimen/mean RLU of 2 positive controls).
Group 0 sample size Number of subjects in the control (unexposed) group: 31
Group 1 sample size Number of subjects in the case (exposed) group: 10

Lab analysis

Sequencing type: 16S

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Roche454

Statistical Analysis

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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, menopause, contraception, smoking behavior

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

Edit History Delete

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Phyu Han

Revision editor(s): WikiWorks

Source: Table 2

Description: Mulivariate odd ratios of species according to different types of HPV

Abundance in Group 1: increased abundance in HPV negative

NCBI	Links
Lactobacillus crispatus

Revision editor(s): WikiWorks

Experiment 4

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects: South Korea

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: Uterus Uterus

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

Group 0 name Corresponds to the control (unexposed) group for case-control studies: HPV presistent and negative
Group 1 name Corresponds to the case (exposed) group for case-control studies: HPV clearance
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: HPV DNA was detected using the Digene HC2 high-risk DNA test (Qiagen, Gaithersburg, MD, USA) with signal amplification and chemiluminescence for 13 types of HR-HPV scored in RLU/PC. A positive result indicated a concentration of 1 pg/ml or higher than the RLU/cutoff ratio (RLU of the specimen/mean RLU of 2 positive controls).
Group 0 sample size Number of subjects in the control (unexposed) group: 26
Group 1 sample size Number of subjects in the case (exposed) group: 15

Lab analysis

Sequencing type: 16S

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Roche454

Statistical Analysis

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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, menopause, contraception, smoking behavior

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged
Chao1 Abundance-based estimator of species richness: unchanged