• Oesophageal squamous cell carcinoma
• microbiota
• periodontitis
• porphyromonas gingivalis
• tooth loss

• Humans
• Esophageal Squamous Cell Carcinoma/complications
• Tooth Loss/complications
• Dysbiosis/complications
• Esophageal Neoplasms/etiology
• Upper Gastrointestinal Tract/pathology
• Microbiota

• Adults
• Periodontal disease
• Risk factors
• Squamous Cell Esophageal Cancer

• Characterization
• Esophageal squamous cell carcinoma
• Leptotrichia
• Oral microbiota
• Tongue coating

• Humans
• Esophageal Squamous Cell Carcinoma/genetics
• Esophageal Neoplasms/pathology
• RNA, Ribosomal, 16S/genetics
• Microbiota/genetics
• Adenocarcinoma/pathology
• Bacteria

• YKK20108 Nanjing health science and technology development special fund project plan
• NMUB2019134 Science and Technology Development Project of Nanjing Medical University

• acetaldehyde
• alcohol
• auto-brewery syndrome
• microbiome
• oral cancer
• risk factors

• adenocarcinoma
• epidemiology
• prevention
• risk factors
• squamous cell carcinoma

• 001 World Health Organization

• Africa
• Fusobacterium
• esophageal cancer
• esophageal squamous cell carcinoma
• microbiome

• Bacteria/genetics
• Esophageal Neoplasms/genetics
• Esophageal Squamous Cell Carcinoma
• Humans
• Kenya
• Microbiota/genetics

• R01 CA239604 NCI NIH HHS
• C98/A24032 Cancer Research UK
• P30 CA082103 NCI NIH HHS
• U24 CA210974 NCI NIH HHS
• R01 CA222862 NCI NIH HHS
• R01 CA230263 NCI NIH HHS
• 001 World Health Organization
• R21 CA191965 NCI NIH HHS
• P01 CA203655 NCI NIH HHS
• P30 CA015704 NCI NIH HHS
• R01 CA227807 NCI NIH HHS
• R00 CA229984 NCI NIH HHS
• R35 CA232128 NCI NIH HHS

Imbalance of oral salivary microbiota has been linked to the pathogenesis of a variety of systemic diseases, and oral bacterial species have been shown to be useful biomarkers for systemic diseases.This study aimed to characterize the alterations of oral microbiota in patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the diagnostic performance of oral microbial biomarkers for ESCC.

The relative abundance of flora in saliva samples was analyzed by 16S rDNA sequencing, and differences in the species present in samples from ESCC patients and healthy controls (HCs) were identified by analyzing species diversity and performing LEfSe analysis. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of the characteristic bacteria individually and in combination.

Differences in bacterial diversity indexes were observed for the saliva of ESCC patients versus HCs (P<0.05), but principal coordinate analysis did not detect a significant difference in the composition of oral microbiota between ESCC patients and HCs (P>0.05). LEfSe analysis showed that Leptotrichia, Porphyromonas (Pg), Streptococcus, Rothia, Lactobacillus and Peptostreptococcus were more abundant in ESCC patient saliva than in HC saliva, whereas Haemophilus, Alloprevotella (All), Prevotella_7, Prevotella (Pre), Prevotella_6, Pasteurellaceae and Pasteurellales were significantly less abundant in ESCC patient saliva (P<0.05). From ROC curve analysis, Pg could detect ESCC with an area under the ROC curve (AUC) of 0.599, sensitivity of 62.2%, and specificity of 70%, whereas the ratio of Pg/Pre had an AUC of 0.791, sensitivity of 93.3%, and specificity of 62.3%. Moreover, the combination of the Pg/Pre and Pg/All ratios showed further improved diagnostic performance for ESCC (AUC=0.826) and even good sensitivity and specificity for the diagnosis of early ESCC (68.2% and 86%, respectively; AUC=0.786).

This study shows that Pg in saliva can be used as a characteristic marker of ESCC, and the ratios of Pg/Pre and Pg/All offered significantly improved diagnostic performance, especially for early ESCC.

• Humans
• Esophageal Squamous Cell Carcinoma/diagnosis
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/pathology
• Porphyromonas gingivalis/genetics
• Saliva/microbiology
• Prevotella
• Carcinoma, Squamous Cell/diagnosis
• Biomarkers

Commensal microbes cross talk with their colonized mucosa. We show that microbes and their cell wall components induce an inflammatory response in cultured human mucosal cells derived from the nonmalignant nasopharyngeal epithelium (NNE) cells in vitro. NNE cells show significant induction of NF-κB with nuclear shuttling and inflammatory gene response when exposed to Gram-positive bacteria (streptococci) or peptidoglycan (PGN), a component of the Gram-positive bacterial cell wall. This response is abrogated in nasopharyngeal carcinoma (NPC)–derived cell lines. The inflammatory response induced by NF-κB signaling was blocked at two levels in the tumor-derived cells. We found that NF-κB was largely trapped in lipid droplets (LDs) in the cytoplasm of the NPC-derived cells, while the increased expression of lysine-specific histone demethylase 1 (LSD1, a repressive nuclear factor) reduces the response mediated by remaining NF-κB at the promoters responding to inflammatory stimuli. This refractory response in NPC cells might be a consequence of long-term exposure to microbes in vivo during carcinogenic progression. It may contribute to the decreased antitumor immune responses in NPC, among others despite heavy T-helper cell infiltration, and thus facilitate tumor progression.

The aim is to explore the predictive value of salivary bacteria for the presence of esophageal squamous cell carcinoma (ESCC). Saliva samples were obtained from 178 patients with ESCC and 101 healthy controls, and allocated to screening and verification cohorts, respectively. In the screening phase, after saliva DNA was extracted, 16S rRNA V4 regions of salivary bacteria were amplified by polymerase chain reaction (PCR) with high-throughput sequencing. Highly expressed target bacteria were screened by Operational Taxonomic Units clustering, species annotation and microbial diversity assessment. In the verification phase, the expression levels of target bacteria identified in the screening phase were verified by absolute quantitative PCR (Q-PCR). Receiver operating characteristic (ROC) curves were plotted to investigate the predictive value of target salivary bacteria. LEfSe analysis revealed higher proportions of Fusobacterium, Streptococcus and Porphyromonas, and Q-PCR assay showed significantly higher numbers of Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in patients with ESCC, when compared with healthy controls (all P < 0.05). The areas under the ROC curves for Streptococcus salivarius, Fusobacterium nucleatum, Porphyromonas gingivalis and the combination of the three bacteria for predicting patients with ESCC were 69%, 56.5%, 61.8% and 76.4%, respectively. The sensitivities corresponding to cutoff value were 69.3%, 22.7%, 35.2% and 86.4%, respectively, and the matched specificity were 78.4%, 96.1%, 90.2% and 58.8%, respectively. These highly expressed Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in the saliva, alone or in combination, indicate their predictive value for ESCC.

• ECA, esophageal carcinoma
• ESCC, esophageal squamous cell carcinoma
• Esophageal squamous cell carcinoma (ESCC)
• HTS, high-throughput sequencing
• KW, Kruskal-Wallis
• LDA, linear discriminant analysis
• OTUs, Operational Taxonomic Units
• PCR, polymerase chain reaction
• Predictive value
• Q-PCR, quantitative PCR
• Quantitative polymerase chain reaction (Q-PCR)
• ROC, receiver operating characteristic
• Receiver operating characteristic (ROC) curves
• Salivary bacteria

• 25004 Cancer Research UK
• Malawi Cancer Consortium
• Division of Cancer Epidemiology and Genetics, National Cancer Institute

Oral health and genetic factors can independently influence the risk of developing esophageal squamous cell carcinoma (ESCC).

The primary objective of this study was to investigate the interactive effects of oral health and genetic factors on ESCC risk.

This was a matched case-control study with 927 ESCC patients and 1701 matched controls. We selected 101 candidate single nucleotide polymorphisms (SNPs) from 59 genes that were associated with ESCC. Oral health was assessed based on tooth-brushing frequency, tooth loss, and age at the time of first tooth loss. An unconditional logistic regression model was employed in which SNP–oral health interactions were assessed as risk factors for ESCC, after adjusting for age and sex. A genetic risk score (GRS) analysis was conducted.

The association between GRS and ESCC and the synergistic effect of GRS and oral health on ESCC were examined. Daily frequency of tooth-brushing was found to interact with 5 SNPs, rs3765524, rs753724, rs994771, rs3781264, and rs11187842, to increase the risk of ESCC. In particular, individuals with genotype TT of rs3765524 who brushed their teeth less than twice a day had a 5.13-times higher risk of ESCC than those with genotype CC who brushed their teeth at least twice a day. Furthermore, tooth loss interacted with two SNPs: rs1159918 from ADH1B and rs3813867 from CYP2E1.

Oral health may interact with genetic factors increasing ESCC risk, which provides new insights into the relationship between ESCC and gene–lifestyle interactions which can be used for disease prevention.

• Tooth brushing
• esophageal carcinoma (EC)
• esophageal squamous cell carcinoma (ESCC)
• meta-analysis

Eastern Africa is one of several regions affected by high incidence rates of esophageal squamous cell carcinoma (ESCC). A unique epidemiologic feature of ESCC in Eastern Africa is the high incidence in young people, with one-third of cases diagnosed at age < 45 years. This study aimed to investigate risk factors for early-onset ESCC in Tanzania through a secondary analysis of a matched case-control study.

Data from Tanzania show esophageal cancer risk factors in East Africa may differ across age groups.

Dietary patterns and symptoms research among Chinese with esophageal squamous cell carcinoma (ESCC) and its precursor lesions is limited, especially as it relates to multiple food consumption and multiple co-occurring symptoms. The aim of our study was to identify the dietary patterns and severity of symptom classes with the risk of esophageal squamous cell carcinoma and its histological precursor lesions, and develop a risk prediction model for different stages of esophageal disease.

We analyzed data from a multicenter cross-sectional study carried out in ESCC high incidence areas between 2017 and 2018, which included 34,707 individuals aged 40–69 years. Dietary patterns and severity of symptom classes were derived by applying a latent class analysis (LCA). A multiple logistic regression model was used to derive the odds ratio (ORs) and corresponding 95% confidence intervals (CIs) for ESCC and the different stages of esophageal disease according to the dietary patterns and severity of symptom classes identified. We built the risk prediction model by using a nomogram.

We identified five dietary patterns and three severity of symptom classes. The dietary patterns were classified as follows: “Healthy”, “Western”, “Lower consumers-combination”, “Medium consumers-combination” and “Higher consumers-combination” patterns based on the intake of foods such as red meat, vegetables and fruits. The severity of symptoms was categorized into “Asymptomatic”, “Mild symptoms” and “Overt symptoms” classes based on health-related symptoms reported by the participants. Compared to the “Healthy” pattern, the other four patterns were all associated with an increased risk of esophageal disease. Similarly, the other two symptom classes present different degrees of increased risk of esophageal disease compared to the “Asymptomatic”. The nomograms reflect the good predictive ability of the model.

Among individuals aged 40–69 years in high incidence regions of upper gastrointestinal cancer, the results supplied that subjects with diets rich in livestock and poultry meat and low in fruits and vegetables and subjects with typical symptoms were at increased ESCC risk. The findings highlight the importance of considering food and symptom combinations in cancer risk evaluation.

The online version contains supplementary material available at 10.1186/s12885-022-09206-y.

• Brazil
• Noncommunicable Diseases
• Risk Factors
• Tooth Loss

• Esophageal cancer
• epidemiology
• esophageal squamous cell carcinoma
• risk factors
• screening

• esophageal adenocarcinoma
• esophageal cancer
• esophageal microbiome
• esophageal squamous cell carcinoma
• oral health
• oral microbiome

• Intramural Research Program NCI NIH HHS

Previous studies have shown the association between Campylobacter species infection and that environmental factors, poor oral hygiene in particular, are linked to an increased risk of esophageal cancer (EC). However, no study has reported on these factors in Thailand. Thus, this study’s objective was to evaluate the impact of the relationship between Campylobacter infection and environmental factors on EC incidence in the population of Thailand.

Data from a case–control study were collected from 105 newly diagnosed EC cases and 105 controls recruited from 2007 to 2017. Infection with Campylobacter spp. was detected in the formalin-fixed paraffin-embedded (FFPE) tissue of EC taken from gastroesophageal biopsy specimens obtained from the participants, and evaluated using TaqMan^® real-time PCR. Multivariable logistic regression was performed to calculate the odds ratios (ORs) and perform data analysis.

Smoking, alcohol use, a family history of cancer, history of gastroesophageal reflux disease, poor oral hygiene and Campylobacter spp. infection were shown to be significant risk factors for EC (p  <  0.05). The combination of poor oral hygiene and infection with Campylobacter spp. constituted significant risk for EC (p  <  0.001). In addition, the risk of EC in subjects co-infected with C. rectus and C. concisus that practiced poor oral hygiene was even higher and was significant (ORadj  =  4.7; 95% CI 2.41–9.98; p  =  0.003).

In Thailand, the major risk factors for EC are smoking status, alcohol drinking, family history of cancer, GERD, poor oral hygiene and Campylobacter spp. infection. This study found Campylobacter spp. prevalence to be associated with EC and appears to be enhanced by poor oral hygiene, suggesting that a combination of poor oral hygiene and Campylobacter species infection may together act as an important etiological risk factor for EC.

The online version contains supplementary material available at 10.1186/s40001-021-00561-3.

• Campylobacter species
• Esophageal cancer
• Poor oral hygiene
• Risk factor

• oral health
• tooth brushing
• tooth loss
• dmft
• upper gastrointestinal cancers

• Adult
• Esophageal Neoplasms/epidemiology
• Esophageal Neoplasms/prevention & control
• Female
• Humans
• Incidence
• Iran/epidemiology
• Male
• Middle Aged
• Oral Health/statistics & numerical data
• Oral Hygiene/statistics & numerical data
• Periodontal Diseases/epidemiology
• Prospective Studies
• Risk Assessment/methods
• Risk Assessment/statistics & numerical data
• Risk Factors
• Self Report/statistics & numerical data
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/prevention & control

• 001 World Health Organization
• Z99 CA999999 Intramural NIH HHS
• C20/A5860 Cancer Research UK

• Oral health
• cancer
• tooth loss

• ZIA CP000112 Intramural NIH HHS

• Tanzania
• esophageal cancer
• fluorosis
• oral health

• 001 World Health Organization
• Centre International de Recherche sur le Cancer
• Wereld Kanker Onderzoek Fonds

• UADT cancers
• cancer risk
• gastric cancer
• meta-analysis
• toothbrushing

• Esophageal SCC
• IL-6
• P. gingivalis
• microbiome
• prognosis

• Adult
• Aged
• Animals
• Disease Progression
• Esophageal Neoplasms/microbiology
• Esophageal Neoplasms/pathology
• Esophageal Squamous Cell Carcinoma/microbiology
• Esophageal Squamous Cell Carcinoma/pathology
• Humans
• Interleukin-6/metabolism
• Mice, Inbred C57BL
• Microbiota
• Middle Aged
• Mouth/microbiology
• Neoplasm Invasiveness
• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/pathology
• Porphyromonas gingivalis/physiology
• Prognosis
• Signal Transduction
• Survival Analysis
• Xenograft Model Antitumor Assays
• Mice

• CMRPG6H0561-2 Chiayi Chang Gung Memorial Hospital

• African oesophageal cancer corridor
• Epidemiology
• Microbiome
• Microbiota
• Oesophageal squamous cell carcinoma

• marginal gingival leukoplakia, proliferative verrucous leukoplakia
• ring around the collar
• verrucous carcinoma
• verrucous hyperplasia

Epidemiologic and cancer control studies on the association of periodontal disease and cancer risk mostly suggest a positive association with overall cancer risk and certain specific types of cancer. These findings are generally consistent among cross‐sectional and longitudinal studies. In this paper, we review epidemiologic studies and current knowledge on periodontal disease and cancer, with a focus on those studies conducted in the years following the Joint European Federation of Periodontology/American Academy of Periodontology Workshop on “Periodontitis and Systemic Diseases” in November 2012. This review also explores the role of chronic inflammation as a biologically plausible mechanistic link between periodontal disease and risk of cancer. Furthermore, it highlights studies that have examined the potential importance of certain periodontal pathogens in this association.

• cancer risk
• epidemiology
• inflammation
• missing teeth
• periodontal disease
• tooth loss

• Cancer
• Mortality
• Periodontitis
• Smoking

• chemokines
• cytokines
• esophageal cancer
• inflammation

• denture
• edentulism
• elderly
• meta-analysis
• tooth

• Aged
• Dental Care
• Dental Caries
• Humans
• Iran
• Oral Health
• Tooth Loss

The purpose of this project was to determine the level of mouth cancer awareness and to investigate the associated factors in a United Kingdom (UK) general population sample.

Adult Dental Health Survey (2010) was conducted in a sample of 3,353 adult residents in the Grampian region of the UK (adjusted participation rate 58%). Participants completed a questionnaire consisting of questions on oral health, health behaviour, quality of life and cancer awareness.

Overall, 81% of participants were aware of mouth cancer. This was associated with younger age, higher levels of education and better general health. Current smokers and alcohol drinkers were more aware of mouth cancer. When asked about risk factors for mouth cancer, the following were identified by the respondents: smoking (84%), poor oral hygiene (60%), drinking alcohol heavily (59%), poor diet (37%), stress (15%), being overweight (6%), drinking hot liquids (5%), eating spicy food (3%), using mouthwash (2%) and kissing someone (1%). Smokers were more likely to identify smoking as a risk factor for mouth cancer. Similarly, those who consumed alcohol almost daily were more likely to identify heavy alcohol drinking as a risk factor.

Awareness of mouth cancer is high in respondents from the general population, and participants were able to identify the most important risk factors. Knowledge of tobacco and alcohol as risk factors was highest amongst those exposed to them. The study proposed that the prevention strategies should focus not only on increasing knowledge, but also on changing health behaviour.

• alcohol drinking
• awareness
• mouth cancer
• risk factors
• tobacco

• 16S ribosomal RNA (rRNA) gene sequencing
• diversity
• esophageal squamous cell carcinoma
• gastric cardia adenocarcinoma
• microbiota

• Africa
• cancer
• dental fluorosis
• esophageal cancer
• oral health

• Africa/epidemiology
• Case-Control Studies
• Esophageal Neoplasms/epidemiology
• Esophageal Squamous Cell Carcinoma/epidemiology
• Female
• Fluorosis, Dental/epidemiology
• Humans
• Male
• Middle Aged
• Oral Health/statistics & numerical data
• Prevalence

• 001 World Health Organization
• R21 CA191965 NCI NIH HHS

• drinking water
• esophageal precancerous lesions
• esophageal squamous dysplasia
• house heating method
• oral health
• population-based

• Cohort study
• dysplasia
• tooth loss
• upper gastrointestinal cancer

• Adult
• Aged
• Cardia/pathology
• Esophageal Neoplasms/mortality
• Esophageal Neoplasms/pathology
• Esophageal Squamous Cell Carcinoma/mortality
• Esophageal Squamous Cell Carcinoma/pathology
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Nutrition Surveys
• Proportional Hazards Models
• Prospective Studies
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology
• Tooth Loss/epidemiology

• Epidemiology
• Esophageal Carcinoma
• GCS
• PAH Exposure