Association of high-risk human papillomavirus infection duration and cervical lesions with vaginal microbiota composition

Study information

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Reviewed Marked as Reviewed by Fatima on 2022/03/12
Quality issues

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

33241010

DOI Digital object identifier for electronic documents.

10.21037/atm-20-5832

URI

Authors

Liu J, Luo M, Zhang Y, Cao G, Wang S

Journal

Annals of translational medicine

Year

2020

Keywords:

Cervical cancer, human papillomavirus infection (HPV infection), cervical intraepithelial neoplasia pathological classification, cervical microbiota

Background: Cervical cancer is reportedly caused by the synergistic effects of persistent high-risk human papillomavirus (HPV) infection. Cervical microbiota represent a unique and dynamically changing microecological system that is directly exposed to the vagina. The relationship between HPV and the composition of the cervical microbiome has long been a primary focus of research. Methods: To determine the specific differential florae throughout the process of cervical cancer development, in the present study, 16S rRNA sequencing was combined with KEGG pathway enrichment analysis to analyse five groups of cervical scraping samples with increasing durations of HPV infection and cervical intraepithelial neoplasia pathological classification. Results: The findings revealed that decreasing levels of probiotics, including Shuttleworthia, Prevotella, Lactobacillus, and Sneathia, and increasing levels of pathogenic bacteria, including Dispar, Streptococcus, and Faecalibacterium prausnitzii, could be the direct result of early HPV infection. Other pathogenic bacteria, such as Bifidobacteriaceae, might represent key factors in cancer progression. Additionally, KEGG pathway enrichment analysis indicated that HPV infection directly inhibits multiple pathways, including those of sporulation, porphyrin and chlorophyll metabolism, arginine and proline metabolism, isoquinoline alkaloid biosynthesis, and ansamycin biosynthesis, which may lead to the development of early symptoms of cervical cancer. Biomarkers were predicted based on operational taxonomic unit (OTU) abundance data, and OTU851726 and OTU715913 were undoubtedly the best potential indicators of cervical cancer. Conclusions: The findings of the present study could assist with the development of a guideline for screening new clinical drugs for cervical cancer.

Experiment 1

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/18

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, Fatima, Cynthia Anderson, Peace Sandy

Subjects

Location of subjects

China

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

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

persistent HPV+ with LSIL

Group 1 name Corresponds to the case (exposed) group for case-control studies

persistent HPV+ with HSIL

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

persistent HPV+ infection ( same HPV subtype has infected for >12 months) with high grade squamus intraepithelial lesion

Lab analysis

Sequencing type

16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

Not specified

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).

raw counts

Statistical test

ANOVA

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

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/18

Curator: Cynthia Anderson

Revision editor(s): Fatima, Cynthia Anderson, WikiWorks

Source: Figure 3A

Description: Differential florae types in the comparison of the microbiota between high-risk human papillomavirus (HPV) persistent infection higher-grade squamous intraepithelial lesion (HSIL) and the high-risk HPV persistent infection with lower-grade squamous intraepithelial lesion (LSIL) group

Abundance in Group 1: decreased abundance in persistent HPV+ with HSIL

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Achromobacter
Comamonas
Commensalibacter
Gallicola
Halomonas
Lactococcus
Leuconostoc
Lysobacter
Massilia
Methylobacterium
Nocardioides
Paracoccus
Phascolarctobacterium
Pseudoduganella
Pseudomonas
Solirubrobacter
Stappia
Syntrophococcus
Thermus

Revision editor(s): Fatima, Cynthia Anderson, WikiWorks

Experiment 2

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/18

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

transient HPV+ with LSIL

Group 1 name Corresponds to the case (exposed) group for case-control studies

transient HPV+ with HSIL

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

high-risk HPV transient infection (HPV has regressed within 1 year) with high grade squamus intraepithelial lesion

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).

Not specified

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Source: Figure 3B

Description: comparison of the microbiota between the high-risk HPV persistent infection with LSIL group and high-risk HPV transient infection with HSIL group

Abundance in Group 1: decreased abundance in transient HPV+ with HSIL

NCBI	Quality Control	Links
Lysobacteraceae
[Clostridium] innocuum

Revision editor(s): Cynthia Anderson, WikiWorks

Experiment 3

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

HPV-

Group 1 name Corresponds to the case (exposed) group for case-control studies

transient HPV+ with LSIL

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

high-risk HPV transient infection (HPV has regressed within 1 year) with low grade squamus intraepithelial lesion

Group 0 sample size Number of subjects in the control (unexposed) group

31

Lab analysis

Statistical Analysis

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Source: Figure 3C

Description: Comparison of the microbiota between high-risk HPV transient infection with LSIL group and the non-infected HPV group

Abundance in Group 1: decreased abundance in transient HPV+ with LSIL

NCBI	Quality Control	Links
Sneathia
Shuttleworthella
Veillonella
[Clostridium] innocuum
Megasphaera
Devosia
Lysobacteraceae
Gardnerella

Revision editor(s): Cynthia Anderson, WikiWorks

Experiment 4

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

persistent HPV+ with HSIL

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

high-risk HPV persistent infection with high grade squamus intraepithelial lesion

Lab analysis

Statistical Analysis

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Fatima, Cynthia Anderson, WikiWorks

Source: Figure 3D

Description: Comparison of the microbiota between high-risk HPV persistent infection with HSIL and the non-infected HPV group

Abundance in Group 1: decreased abundance in persistent HPV+ with HSIL

NCBI	Quality Control	Links
Megasphaera
Peptostreptococcus
Shuttleworthella
Sneathia

Revision editor(s): Fatima, Cynthia Anderson, WikiWorks

Experiment 5

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

persistent HPV+ with LSIL

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

persistent HPV+ infection ( same HPV subtype has infected for >12 months) with high grade squamus intraepithelial lesion

Group 0 sample size Number of subjects in the control (unexposed) group

Not specified

Lab analysis

Statistical Analysis

Statistical test

LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)

Not specified

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?

Not specified

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Source: Figure 4A

Description: Abundance analysis of the microbiota between high-risk human papillomavirus (HPV) persistent infection with higher-grade squamous intraepithelial lesion (HSIL) and the high-risk HPV persistent infection with lower-grade squamous intraepithelial lesion (LSIL) group

Abundance in Group 1: increased abundance in persistent HPV+ with HSIL

NCBI	Quality Control	Links
Streptococcus agalactiae

Revision editor(s): Cynthia Anderson, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Source: Figure 4A

Description: Abundance analysis of the microbiota between high-risk human papillomavirus (HPV) persistent infection with higher-grade squamous intraepithelial lesion (HSIL) and the high-risk HPV persistent infection with lower-grade squamous intraepithelial lesion (LSIL) group

Abundance in Group 1: decreased abundance in persistent HPV+ with HSIL

NCBI	Quality Control	Links
Faecalibacterium
Caryophanaceae
Corynebacterium tuberculostearicum
Lawsonella
Erysipelotrichales
Micrococcaceae
Pseudarthrobacter oxydans
Corynebacterium aurimucosum
Peptoniphilus
Actinomycetaceae
Anaerococcus
[Ruminococcus] torques
Prevotella disiens
Nocardiaceae
Dialister
Deinococcota
Actinomycetales
Prevotella
Gardnerella
Deinococci
Leuconostoc
Nitrosomonadaceae
Lysobacterales
Howardella
Finegoldia
Aedoeadaptatus coxii
Bifidobacterium dentium
Staphylococcus
Staphylococcus aureus
Staphylococcaceae
Bacillales
Enterococcus durans
Enterococcus
Enterococcaceae
Ligilactobacillus salivarius
Dialister micraerophilus
Selenomonadales
Negativicutes
Bifidobacteriaceae
Bifidobacteriales
Streptococcaceae

Revision editor(s): Cynthia Anderson, WikiWorks

Experiment 6

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, Cynthia Anderson

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

transient HPV+ with HSIL

Group 1 name Corresponds to the case (exposed) group for case-control studies

persistent HPV+ with LSIL

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

high-risk HPV persistent infection with low grade squamus intraepithelial lesion

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete

Flag for review

Your review change was submitted

Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Source: Figure 4B

Description: Abundance analysis of the microbiota between the high-risk HPV persistent infection with LSIL group and high-risk HPV transient infection with HSIL group

Abundance in Group 1: increased abundance in persistent HPV+ with LSIL

NCBI	Quality Control	Links
[Ruminococcus] torques

Revision editor(s): Cynthia Anderson, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Source: Figure 4B

Description: Abundance analysis of the microbiota between the high-risk HPV persistent infection with LSIL group and high-risk HPV transient infection with HSIL group

Abundance in Group 1: decreased abundance in persistent HPV+ with LSIL

NCBI	Quality Control	Links
Porphyromonas
Trichinella pseudospiralis
Quinella
Tyzzerella
Flavobacterium gelidilacus
Parabacteroides faecis
Dechloromonas

Revision editor(s): Cynthia Anderson, WikiWorks

Experiment 7

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, Cynthia Anderson

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

transient HPV+ with LSIL

Group 1 name Corresponds to the case (exposed) group for case-control studies

transient HPV+ with HSIL

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

high-risk HPV transient infection with high grade squamus intraepithelial lesion

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete

Flag for review

Your review change was submitted

Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Source: Figure 4C

Description: Abundance analysis of the microbiota between high-risk HPV transient infection with HSIL group and high-risk HPV transient infection with LSIL group

Abundance in Group 1: increased abundance in transient HPV+ with HSIL

NCBI	Quality Control	Links
Flavobacteriia
Flavobacteriales
Cloacibacterium
Lactobacillus
Dyella koreensis
Flavobacterium gelidilacus
Dyella
Parabacteroides faecis

Revision editor(s): Cynthia Anderson, WikiWorks

Experiment 8

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, Cynthia Anderson

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

HPV-

Group 1 name Corresponds to the case (exposed) group for case-control studies

transient HPV+ with LSIL

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

high-risk HPV transient infection with low grade squamus intraepithelial lesion

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete

Flag for review

Your review change was submitted

Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Source: Figure 4D

Description: Abundance analysis of the microbiota between high-risk HPV transient infection with LSIL group and the non-infected HPV group

Abundance in Group 1: decreased abundance in transient HPV+ with LSIL

NCBI	Quality Control	Links
Devosia riboflavina
Candidatus Saccharibacteria
Sneathia
Lactobacillus
Pseudomonas
Shuttleworthella
Leptotrichiaceae
Oscillospiraceae
Pseudomonadaceae

Revision editor(s): Cynthia Anderson, WikiWorks

Experiment 9

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, Cynthia Anderson

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

persistent HPV+ with HSIL

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

high-risk HPV persistent infection with low grade squamus intraepithelial lesion

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete

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Your review change was submitted

Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Source: Figure 4E

Description: Abundance analysis of the microbiota between high-risk HPV persistent infection with HSIL and the non-infected HPV group

Abundance in Group 1: increased abundance in persistent HPV+ with HSIL

NCBI	Quality Control	Links
Solirubrobacterales
Morganella

Revision editor(s): Cynthia Anderson, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/03/19

Curator: Cynthia Anderson

Revision editor(s): Cynthia Anderson, WikiWorks

Source: Figure 4E

Description: Abundance analysis of the microbiota between high-risk HPV persistent infection with HSIL and the non-infected HPV group

Abundance in Group 1: decreased abundance in persistent HPV+ with HSIL

NCBI	Quality Control	Links
Prevotella melaninogenica
Dialister
Lactobacillus equicursoris
Prevotella
Sutterella
Peptostreptococcus
Pseudomonas
Peptoniphilus lacrimalis
Prevotella disiens
Oscillospiraceae

Revision editor(s): Cynthia Anderson, WikiWorks