Periodontal pathogens are a risk factor of oral cavity squamous cell carcinoma, independent of tobacco and alcohol and human papillomavirus

Ganly, Ian; Yang, Liying; Giese, Rachel; Hao, Yuhan; Nossa, Carlos W.; Morris, Luc G.T.; Rosenthal, Matthew; Migliacci, Jocelyn; Kelly, Dervla; Tseng, Wenzhi; Hu, Jiyuan; Li, Huilin; Brown, Stuart M.; Pei, Zhiheng

doi:10.1002/ijc.32152

Cited by 125 publications

(164 citation statements)

References 44 publications

(81 reference statements)

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“…Although in healthy humans the Prevotella genus is one of the dominant genera of the salivary microbiome, distinct members of the genus Prevotella are associated with inflammatory diseases and may facilitate carcinogenesis as well [86-88, reviewed by 89,90]. There are, however, contradicting observations regarding the role of Prevotella in the development of oral cancer [14,74,79,[91][92][93][94]. Thus, it remains to be established whether members of the genus Prevotella are opportunistic inhabitants of malignant tumors or play a causative role in oral or colorectal carcinogenesis [95,96].…”

Section: Discussionmentioning

confidence: 99%

A case study of salivary microbiome in smokers and non-smokers in Hungary: analysis by shotgun metagenome sequencing

Wirth

Maróti

Mihók

et al. 2020

Journal of Oral Microbiology

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Objective: To investigate the role of cigarette smoking in disease-development through altering the composition of the oral microbial community. Periodontitis and oral cancer are highly prevalent in Hungary; therefore, the salivary microbiome of smoker and non-smoker Hungarian adults was characterized. Methods: Shotgun metagenome sequencing of salivary DNA samples from 22 individuals (11 non-smokers and 11 current smokers) was performed using the Ion Torrent PGM TM platform. Quality-filtered reads were analysed by both alignment-based sequence similarity searches and genome-centric binning. Results: Prevotella, Veillonella and Streptococcus were the predominant genera in the saliva of both groups. Although the overall composition and diversity of the microbiota were similar, Prevotella was significantly more abundant in salivary samples of current smokers compared to non-smokers. Members of the genus Prevotella were implicated in the development of inflammatory diseases and oral cancer. The abundance of the genus Megasphaera also increased in current smokers, whereas the genera Neisseria, Oribacterium, Capnocytophaga and Porphyromonas were significantly reduced. The data generated by read-based taxonomic classification and genome-centric binning mutually validated the two distinct metagenomic approaches. Conclusion: Smoking-associated dysbiosis of the salivary microbiome in current cigarette smokers, especially increased abundance of Prevotella and Megasphaera genera, may facilitate disease development.

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Section: Discussionmentioning

confidence: 99%

A case study of salivary microbiome in smokers and non-smokers in Hungary: analysis by shotgun metagenome sequencing

Wirth

Maróti

Mihók

et al. 2020

Journal of Oral Microbiology

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“…are opportunistic pathogens that cause diverse infections and show strong connections and contributions to multiple diseases in humans and higher mammals (15). F. nucleatum has garnered significant attention as an "oncobacterium" that contributes to the progression and severity of colorectal cancer and has also been implicated in malignant oral leukoplakia (45), oral squamous cell carcinoma (46,47), and pancreatic cancer (48,49). Because F. nucleatum is an oncomicrobe, F. nucleatum infection studies have shown that administration of the antibiotic metronidazole reduces the tumor burden in human tumor-generated xenografts in mice (22).…”

Section: Discussionmentioning

confidence: 99%

Utilizing Whole Fusobacterium Genomes To Identify, Correct, and Characterize Potential Virulence Protein Families

et al. 2019

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Fusobacterium spp. are Gram-negative, anaerobic, opportunistic pathogens involved in multiple diseases, including a link between the oral pathogen Fusobacterium nucleatum and the progression and severity of colorectal cancer. The identification and characterization of virulence factors in the genus Fusobacterium has been greatly hindered by a lack of properly assembled and annotated genomes. Using newly completed genomes from nine strains and seven species of Fusobacterium, we report the identification and corrected annotation of verified and potential virulence factors from the type 5 secreted autotransporter, FadA, and MORN2 protein families, with a focus on the genetically tractable strain F. nucleatum subsp. nucleatum ATCC 23726 and type strain F. nucleatum subsp. nucleatum ATCC 25586. Within the autotransporters, we used sequence similarity networks to identify protein subsets and show a clear differentiation between the prediction of outer membrane adhesins, serine proteases, and proteins with unknown function. These data have identified unique subsets of type 5a autotransporters, which are key proteins associated with virulence in F. nucleatum. However, we coupled our bioinformatic data with bacterial binding assays to show that a predicted weakly invasive strain of F. necrophorum that lacks a Fap2 autotransporter adhesin strongly binds human colonocytes. These analyses confirm a gap in our understanding of how autotransporters, MORN2 domain proteins, and FadA adhesins contribute to host interactions and invasion. In summary, we identify candidate virulence genes in Fusobacterium, and caution that experimental validation of host-microbe interactions should complement bioinformatic predictions to increase our understanding of virulence protein contributions in Fusobacterium infections and disease. IMPORTANCE Fusobacterium spp. are emerging pathogens that contribute to mammalian and human diseases, including colorectal cancer. Despite a validated connection with disease, few proteins have been characterized that define a direct molecular mechanism for Fusobacterium pathogenesis. We report a comprehensive examination of virulence-associated protein families in multiple Fusobacterium species and show that complete genomes facilitate the correction and identification of multiple, large type 5a secreted autotransporter genes in previously misannotated or fragmented genomes. In addition, we use protein sequence similarity networks and human cell interaction experiments to show that previously predicted noninvasive strains can indeed bind to and potentially invade human cells and that this could be due to the expansion of specific virulence proteins that drive Fusobacterium infections and disease.

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“…Such changes in oral microbiome may be associated with chronic inflammation such as in periodontitis and lead to malignant transformation of the oral mucosa (19)(20)(21). A recent study has also suggested an association between periodontal pathogens and OSCC in NSND (59).…”

Section: Viral Oncogenesis Of Oscc In Nsnd: Should We Incriminate Onlmentioning

confidence: 99%

Arguments to Support a Viral Origin of Oral Squamous Cell Carcinoma in Non-Smoker and Non-Drinker Patients

et al. 2020

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In some western countries, an increasing incidence of oral squamous cell carcinoma (OSCC) has been observed in non-smoker non-drinker patients (NSND), mostly in women with HPV-negative OSCC. In the context of the unknown etiology and mechanisms of tumorigenesis of OSCC in NSND, we discuss data supporting the hypothesis of a viral origin not related to HPV. OSCC from NSND are characterized by an antiviral DNA methylation and gene expression signature. Based on the similar increasing incidence of oral tongue SCC (OTSCC) and oropharyngeal SCC (OPSCC) in young women and men respectively, we hypothesize that changes in sexual behaviors may lead to an increasing incidence of herpesvirus in the oral cavity, especially HSV-2, similarly to what has already been described in HPV-positive OPSCC. Because viral genome integration has not been detected in OSCC from NSND, a "hit and run" viral mechanism involving epigenome deregulation could therefore play a key role at early steps of oral carcinogenesis in this population of patients. In conclusion, epidemiological, clinical and molecular data supports a "hit and run" viral origin of OSCC from NSND.

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Periodontal pathogens are a risk factor of oral cavity squamous cell carcinoma, independent of tobacco and alcohol and human papillomavirus

Cited by 125 publications

References 44 publications

A case study of salivary microbiome in smokers and non-smokers in Hungary: analysis by shotgun metagenome sequencing

A case study of salivary microbiome in smokers and non-smokers in Hungary: analysis by shotgun metagenome sequencing

Utilizing Whole Fusobacterium Genomes To Identify, Correct, and Characterize Potential Virulence Protein Families

Arguments to Support a Viral Origin of Oral Squamous Cell Carcinoma in Non-Smoker and Non-Drinker Patients

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