Periodontal disease, which includes gingivitis and periodontitis, is highly prevalent in adults and disease severity increases with age. The relationship between periodontal disease and oral cancer has been examined for several decades, but there is increasing interest in the link between periodontal disease and overall cancer risk, with systemic inflammation serving as the main focus for biological plausibility. Numerous case-control studies have addressed the role of oral health in head and neck cancer, and several cohort studies have examined associations with other types of cancers over the past decade. For this review, we included studies that were identified from either 11 published reviews on this topic or an updated literature search on PubMed (between 2011 and July 2016). A total of 50 studies from 46 publications were included in this review. Meta-analyses were conducted on cohort and case-control studies separately when at least 4 studies could be included to determine summary estimates of the risk of cancer in relation to 1) periodontal disease or 2) tooth number (a surrogate marker of periodontal disease) with adjustment for smoking. Existing data provide support for a positive association between periodontal disease and risk of oral, lung, and pancreatic cancers; however, additional prospective studies are needed to better inform on the strength of these associations and to determine whether other cancers are associated with periodontal disease. Future studies should include sufficiently large sample sizes, improved measurements for periodontal disease, and thorough adjustment for smoking and other risk factors.

Periodontal Disease, Tooth Loss, and Cancer Risk.

Fusobacterium nucleatum is an oral anaerobe recently found to be prevalent in human colorectal cancer (CRC) where it is associated with poor treatment outcome In mice, hematogenous F nucleatum can colonize CRC tissue using its lectin Fap2, which attaches to tumor-displayed Gal-GalNAc Here, we show that Gal-GalNAc levels increase as human breast cancer progresses, and that occurrence of F nucleatum gDNA in breast cancer samples correlates with high Gal-GalNAc levels We demonstrate Fap2-dependent binding of the bacterium to breast cancer samples, which is inhibited by GalNAc Intravascularly inoculated Fap2-expressing F nucleatum ATCC 23726 specifically colonize mice mammary tumors, whereas Fap2-deficient bacteria are impaired in tumor colonization Inoculation with F nucleatum suppresses accumulation of tumor infiltrating T cells and promotes tumor growth and metastatic progression, the latter two of which can be counteracted by antibiotic treatment Thus, targeting F nucleatum or Fap2 might be beneficial during treatment of breast cancer High levels of Fusobacterium nucleatum have been associated with poor overall survival in patients with colorectal and esophageal cancer Here, the authors show that F nucleatum is abundant in breast cancer samples and that the colonization by F nucleatum accelerates tumor growth and metastasis in preclinical breast cancer models

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Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression

Toothbrushing is considered fundamental self-care behavior for maintenance of oral health, and brushing twice a day has become a social norm, but the evidence base for this frequency is weak. This systematic review and meta-analysis aims to assess the effect of toothbrushing frequency on the incidence and increment of carious lesions. Medline, Embase, Cinahl, and Cochrane databases were searched. Screening and quality assessment were performed by 2 independent reviewers. Three different meta-analyses were conducted: 2 based on the caries outcome reported in the studies (incidence and increment) with subgroup analyses of categories of toothbrushing frequency; another included all studies irrespective of the caries outcome reported with the type of dentition as subgroups. Meta-regression was conducted to assess the influence of sample size, follow-up period, diagnosis level for carious lesions, and methodological quality of the articles on the effect estimate. Searches retrieved 5,494 titles: after removing duplicates, 4,305 remained. Of these, 74 were reviewed in full, but only 33 were eligible for inclusion. Self-reported infrequent brushers demonstrated higher incidence (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.34 to 1.69) and increment (standardized mean difference [SMD], 0.28; 95% CI: 0.13 to 0.44) of carious lesions than frequent brushers. The odds of having carious lesions differed little when subgroup analysis was conducted to compare the incidence between ≥2 times/d vs <2 times/d (OR: 1.45; 95% CI: 1.21 to 1.74) and ≥1 time/d vs <1 time/d brushers (OR: 1.56; 95% CI: 1.37 to 1.78). When meta-analysis was conducted with the type of dentition as subgroups, the effect of infrequent brushing on incidence and increment of carious lesions was higher in deciduous (OR: 1.75; 95% CI: 1.49 to 2.06) than permanent dentition (OR: 1.39; 95% CI: 1.29 to 1.49). Findings from meta-regression indicated that none of the included variables influenced the effect estimate.

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Effect of Toothbrushing Frequency on Incidence and Increment of Dental Caries: A Systematic Review and Meta-Analysis.

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)-adjustedP-value (q-value) 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 generaCorynebacterium(fold change [FC], 0.58; 95% confidence interval [CI], 0.41-0.80;q = .06) andKingella(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 commensalCorynebacteriumandKingellais associated with decreased risk of HNSCC, with potential implications for cancer prevention.

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

The human microbiome, which includes the collective genome of all bacteria, archaea, fungi, protists, and viruses found in and on the human body, is altered in many diseases and may substantially affect cancer risk. Previously detected associations of individual bacteria (e.g., Helicobacter pylori), periodontal disease, and inflammation with specific cancers have motivated studies considering the association between the human microbiome and cancer risk. This short review summarises microbiome research, focusing on published epidemiological associations with gastric, oesophageal, hepatobiliary, pancreatic, lung, colorectal, and other cancers. Large, prospective studies of the microbiome that employ multidisciplinary laboratory and analysis methods, as well as rigorous validation of case status, are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, screening, and treatment.

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Epidemiologic studies of the human microbiome and cancer.

Background 
Many epidemiological studies have found a positive association of periodontal disease (PD) with risk of head and neck cancer (HNC), but the findings are varied or even contradictory. In this work, we performed a meta-analysis to ascertain the relationship between PD and HNC risk.


Methods 
We searched the PubMed, Embase, and Cochrane Library databases for relevant observational studies on the association between PD and HNC risk published up to March 23, 2013. Data from the included studies were extracted and analyzed independently by two authors. Meta-analysis was performed using RevMan 5.2 software.


Results 
We obtained seven observational studies involving two cohort and six case-control studies. Random-effects meta-analysis indicated a significant association between PD and HNC risk (odds ratio = 2.63, 95% confidence interval = 1.1.68 - 4.14; p < 0.001), with sensitivity analysis showing that the result was robust. Subgroup analyses based on adjustment for covariates, study design, PD assessment, tumor site, and ethnicity also revealed a significant association.


Conclusions 
Based on currently evidence, PD is probably a significant and independent risk factor of HNC.

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Periodontal disease and risk of head and neck cancer: a meta-analysis of observational studies.

Meta-analysis on the association between toothbrushing and head and neck cancer

Background: Many studies have been conducted to explore the association between interleukin (IL)-1β C-511T polymorphism and risk of chronic periodontitis (CP) but with different or even contradictory results. A meta-analysis was performed to further explore their association.Methods: PubMed, Chinese National Knowledge Infrastructure, and EMBASE were searched up to September 30, 2014 for relevant case-control studies. Two authors (D-YL and L-YX) independently selected studies and extracted data from included studies. The meta-analysis was performed using comprehensive meta-analysis software.Results: Nineteen case-control studies involving 2,173 patients with CP and 3,900 healthy controls were included. Using a random-effects meta-analysis model, a non-significant association between IL-1β C-511T polymorphism and CP was identified (T versus C: odds ratio [OR] = 1.03, 95% confidence interval [CI] = 0.85 to 1.25; TT versus CC: OR = 1.03, 95% CI = 0.72 to 1.46; CT versus CC: OR = 0.96, 95% CI = 0.71 to 1.30; C...

Meta-Analysis of Association Between Interleukin-1β C-511T Polymorphism and Chronic Periodontitis Susceptibility.

Objective: Both tooth loss and dementia are age-related and frequently-occurring diseases. Increasing attention has been given to explore the pathogenesis related to oral-brain function disorders. The present study was performed to evaluate the association between tooth loss and dementia through a dose-response meta-analysis. Methods: Relevant cohort studies were searched from online databases up until June 20, 2018, which examined the association between tooth loss and the risk of dementia. Literature selection according to inclusion and exclusion criteria, as well as data extraction from included studies were completed independently by two reviewers. Data syntheses in this meta-analysis were performed using Stata 12.0 software. Results: A total of 8 cohort studies were included, containing a total of 14,362 samples and 2,072 dementia patients. The result of the meta-analysis indicated that patients with tooth loss faced a 1.34 times greater risk of developing dementia (RR = 1.34,95% CI = 1.19-1.51). The result from this dose-response meta-analysis in a linear model, suggested that every missed tooth might increase the risk of dementia by 1.01 times (RR = 1.01, 95%CI = 1.00-1.02). Further subgroup analyses pointed out that tooth loss patients without dentures may have a higher risk of dementia than those with dentures (with denture: RR = 0.98, 95% CI = 0.87-1.10; without denture: RR = 1.53, 95% CI = 1.19-1.97); at the same time, the study design, study area and education level of the study participants, might also have some effect on the results. Conclusions: Tooth loss may be a risk factor for the development of dementia. In addition, there is a dose-response relationship with the increase of missing teeth.

Tooth Loss Is Associated With Increased Risk of Dementia and With a Dose-Response Relationship.

Backgroud
Epidemiological studies have shown that tooth loss is associated with risk of head and neck cancer (HNC); however, the results were inconsistent. Therefore, we conducted a meta-analysis to ascertain the relationship between tooth loss and HNC.

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Wei-Dong Leng

Papers

Periodontal disease and risk of head and neck cancer: a meta-analysis of observational studies.

Meta-analysis on the association between toothbrushing and head and neck cancer

Meta-Analysis of Association Between Interleukin-1β C-511T Polymorphism and Chronic Periodontitis Susceptibility.

Tooth Loss Is Associated With Increased Risk of Dementia and With a Dose-Response Relationship.

Tooth loss and head and neck cancer: a meta-analysis of observational studies.