Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer

From BugSigDB
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Hayes RB, Ahn J, Fan X, Peters BA, Ma Y, Yang L, Agalliu I, Burk RD, Ganly I, Purdue MP, Freedman ND, Gapstur SM, Pei Z
Journal
JAMA oncology
Year
2018
Importance: Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC. Objective: To prospectively examine associations between the oral microbiome and incident HNSCC. Design, Setting, and Participants: This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline. Exposures: Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P-value (q-value) <.10 were considered significant. Main Outcomes and Measures: Incident HNSCC. Results: The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco smokers, tended to have greater alcohol consumption (among drinkers), and to be positive for oral carriage of papillomavirus-16. Overall microbiome composition was not associated with risk of HNSCC. Greater abundance of genera Corynebacterium (fold change [FC], 0.58; 95% confidence interval [CI], 0.41-0.80; q = .06) and Kingella (FC, 0.63; 95% CI, 0.46-0.86; q = .08) were associated with decreased risk of HNSCC, potentially owing to carcinogen metabolism capacity. These findings were consistent for both cohorts and by cohort follow-up time. The observed relationships tended to be stronger for larynx cancer and for individuals with a history of tobacco use. Conclusions and Relevance: This study demonstrates that greater oral abundance of commensal Corynebacterium and Kingella is associated with decreased risk of HNSCC, with potential implications for cancer prevention.

Experiment 1


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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Lwaldron, Claregrieve1, WikiWorks, Victoria

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
Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Head and neck squamous cell carcinoma carcinoma of the head and neck,craniocervical region squamous cell carcinoma,head and neck squamous cell carcinoma,HNSCC,SCCHN,squamous cell carcinoma of head and neck,squamous cell carcinoma of the head and neck,squamous cell carcinoma, head and neck,squamous cell carcinomas of head and neck,Head and neck squamous cell carcinoma
Group 0 name Corresponds to the control (unexposed) group for case-control studies
controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
HNSCC
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
histologically confirmed incident HNSCC including oral cavity, pharynx and larynx. (excluding salivary glands & nasopharynx)
Group 0 sample size Number of subjects in the control (unexposed) group
254
Group 1 sample size Number of subjects in the case (exposed) group
129

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
DESeq2
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.1
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
age, ethnic group, date, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, alcohol drinking, smoking behavior, sex

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged
Richness Number of species
unchanged

Signature 1

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

Curated date: 2021/01/10

Curator: Utsav Patel

Revision editor(s): Claregrieve1, WikiWorks

Source: Table 2

Description: Differential microbial abundance between controls and HNSCC patients

Abundance in Group 1: increased abundance in HNSCC

NCBI Quality ControlLinks
Actinomycetota

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

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

Curated date: 2021/01/10

Curator: Utsav Patel

Revision editor(s): Claregrieve1, WikiWorks

Source: Table 2

Description: Differential microbial abundance between controls and HNSCC patients

Abundance in Group 1: decreased abundance in HNSCC

NCBI Quality ControlLinks
Betaproteobacteria
Capnocytophaga leadbetteri
Corynebacterium
Kingella
Hoylesella nanceiensis
Selenomonas sputigena

Revision editor(s): Claregrieve1, WikiWorks

Experiment 2


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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Squamous cell carcinoma carcinoma, squamous cell, malignant,epidermoid carcinoma,epidermoid cell cancer,malignant epidermoid cell neoplasm,malignant epidermoid cell tumor,malignant squamous cell neoplasm,malignant squamous cell tumor,squamous carcinoma,squamous cell cancer,squamous cell carcinoma,squamous cell carcinoma (morphologic abnormality),squamous cell carcinoma NOS (morphologic abnormality),squamous cell epithelioma,Squamous cell carcinoma
Group 1 name Corresponds to the case (exposed) group for case-control studies
Larynx cancer cases
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
histologically confirmed incident HNSCC involving the larynx
Group 1 sample size Number of subjects in the case (exposed) group
58

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, alcohol drinking, sex, smoking status


Signature 1

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

Curated date: 2021/01/10

Curator: Utsav Patel

Revision editor(s): Claregrieve1, WikiWorks

Source: Table 2, Supplementary Table 6, Text

Description: Differential microbial abundance between controls and larynx cancer patients

Abundance in Group 1: decreased abundance in Larynx cancer cases

NCBI Quality ControlLinks
Abiotrophia
Betaproteobacteria
Capnocytophaga
Corynebacterium
Kingella
Kingella denitrificans
Neisseria
Neisseriales
Streptococcus sanguinis

Revision editor(s): Claregrieve1, WikiWorks

Experiment 3


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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Pharynx cancer cases
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
histologically confirmed incident HNSCC involving the pharynx
Group 1 sample size Number of subjects in the case (exposed) group
30

Lab analysis

Statistical Analysis

Signature 1

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

Curated date: 2021/01/10

Curator: Utsav Patel

Revision editor(s): Claregrieve1, WikiWorks

Source: Table 2, Supplementary Table 6, Text

Description: Differential microbial abundance between controls and pharynx cancer patients

Abundance in Group 1: decreased abundance in Pharynx cancer cases

NCBI Quality ControlLinks
Actinomyces oris
Betaproteobacteria
Corynebacterium
Kingella
Neisseriales
Veillonella denticariosi

Revision editor(s): Claregrieve1, WikiWorks

Experiment 4


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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Oral cavity cancer cases
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
histologically confirmed incident HNSCC involving the oral cavity
Group 1 sample size Number of subjects in the case (exposed) group
41

Lab analysis

Statistical Analysis

Signature 1

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

Curated date: 2021/01/10

Curator: Utsav Patel

Revision editor(s): Claregrieve1, WikiWorks

Source: Table 2, Supplementary Table 6, Text

Description: Differential microbial abundance between controls and oral cavity cancer patients

Abundance in Group 1: increased abundance in Oral cavity cancer cases

NCBI Quality ControlLinks
Actinomyces

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

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

Curated date: 2021/01/10

Curator: Utsav Patel

Revision editor(s): Claregrieve1, WikiWorks

Source: Table 2, Supplementary Table 6, Text

Description: Differential microbial abundance between controls and oral cavity cancer patients

Abundance in Group 1: decreased abundance in Oral cavity cancer cases

NCBI Quality ControlLinks
Neisseria sicca
Parvimonas micra

Revision editor(s): Claregrieve1, WikiWorks