Chronic Inflammation as a Link between Periodontitis and Carcinogenesis

Abstract

Periodontitis is characterized by a chronic inflammation produced in response to a disease-associated multispecies bacterial community in the subgingival region. Although the inflammatory processes occur locally in the oral cavity, several studies have determined that inflammatory mediators produced during periodontitis, as well as subgingival species and bacterial components, can disseminate from the oral cavity, contributing therefore, to various extraoral diseases like cancer. Interestingly, carcinogenesis associated with periodontal species has been observed in both the oral cavity and in extra oral sites. In this review, several studies were summarized showing a strong association between orodigestive cancers and poor oral health, presence of periodontitis-associated bacteria, tooth loss, and clinical signs of periodontitis. Proinflammatory pathways were also summarized. Such pathways are activated either by mono- or polymicrobial infections, resulting in an increase in the expression of proinflammatory molecules such as IL-6, IL-8, IL-1β, and TNF-α. In addition, it has been shown that several periodontitis-associated species induce the expression of genes related to cell proliferation, cell cycle, apoptosis, transport, and immune and inflammatory responses. Intriguingly, many of these pathways are linked to carcinogenesis. Among them, the activation of Toll-like receptors (TLRs) and antiapoptotic pathways (such as the PI3K/Akt, JAK/STAT, and MAPK pathways), the reduction of proapoptotic protein expression, the increase in cell migration and invasion, and the enhancement in metastasis are addressed. Considering that periodontitis is a polymicrobial disease, it is likely that mixed species promote carcinogenesis both in the oral cavity and in extra oral tissues and probably—as observed in periodontitis—synergistic and/or antagonistic interactions occur between microbes in the community. To date, a good amount of studies has allowed us to understand how monospecies infections activate pathways involved in tumorigenesis; however, more studies are needed to determine the combined effect of oral species in carcinogenesis.

Oral health and gastrointestinal cancer: A nationwide cohort study

“…The dissemination of oral bacteria by swallowing saliva, which contains a large number of bacteria, could explain its involvement in inflammation in the GI tract (Nasidze, Li, Quinque, Tang, & Stoneking, 2009; Socransky & Haffajee, 2005). Second, local inflammation caused by poor oral hygiene could promote systemic inflammation and elevate the level of circulating inflammatory markers (Hoare, Soto, Rojas‐Celis, & Bravo, 2019; Michaud, Fu, Shi, & Chung, 2017). These key molecules in the inflammatory process, such as tumour necrosis factor‐α and interleukin‐6‐induced signalling, have been shown to join in both the initiation and progression of malignancies (Landskron, De la Fuente, Thuwajit, Thuwajit, & Hermoso, 2014).…”

Increased Risk of Chronic Periodontitis in Chronic Rhinosinusitis Patients: A Longitudinal Follow-Up Study Using a National Health-Screening Cohort

“…As CP is a widespread immunoinflammatory condition, an association between CRS and CP has been proposed. This was mainly attributed to increased levels of pro-inflammatory mediators, such as interleukin (IL)-1, IL-6, and tumor necrosis factor-α in the plasma [19]. Therefore, we sought to investigate the association between CRS and CP in a large population cohort.…”

Treatment with Luteolin Improves Lipopolysaccharide-Induced Periodontal Diseases in Rats

“…The pathogenic developments of inflammatory periodontal diseases are originated by subgingival plaque microflora and factors such as LPS derived from specific pathogens [ 31 ]. Locally, this inflammatory condition promotes tissue damage, thus causing the morphological alteration of the periodontium [ 32 ]. In particular, tissue damage is associated with the formation of edema and inflammatory cell infiltration with clear damage to gingivomucosal architecture [ 12 , 33 ].…”