# The Link between Periodontal Disease and Oral Cancer--A Certainty or a Never-Ending Dilemma?
###### Abstract
Under physiological settings, there is a delicate balance between the local immune response and the microbiota [31]. When all elements of the microbiota are altered after colonization by a \"keystone\" pathogen such as _P. gingivalis_, the pathogenicity of the entire community is elevated, and the tissue homeostasis is altered. Bacterial cells play a role in the pathogenesis of periodontitis through exotoxins, enzymes, and metabolites, of which exotoxins and leukotoxins intervene in polymorphonuclear leukocytes (PMN), destroy the leukocytes in the gingival groove, and cause colonization and invasion of the periodontal tissue [30; 32]. Gingival connective tissue, periodontal ligament, and alveolar bone are all destroyed by inflammatory mediators. The loss of the outer cementoblast layer produces root surface changes, resulting in superficial cement resorption lesions. Endotoxins, which are produced by bacteria, irritate soft tissue and impede the activation of healing mechanisms [33; 34]. Specific and non-specific immunity complement each other. The inflammation that remains limited at the gingival level is the result of a balanced symbiosis between the biofilm and the host tissues, and the development of PD is the result of the imbalance of such symbiosis, which is modified by the environment and genetic factors. Pro-inflammatory cytokines are those produced during an inflammatory response and promote its progression, such as interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)), IL-12, IL-18, interferons (IFN), and macrophage granulocytes [35; 36]. Anti-inflammatory cytokines inhibit the inflammatory process by their ability to suppress gene expression for pro-inflammatory cytokines and inhibit the effects of inflammatory mediators IL-4, IL-10, IL-13, IL-16, and transforming growth factor (TGF) [37; 38]. Activation of the biochemical mechanisms of cytokine secretion targets the signaling mechanisms due to interference between the associated microbial molecular pattern (lipopolysaccharide-charides, fimbiae) and the pattern of receptor recognition (toll-like receptors, nucleotide-binding, and oligomerization domain-like receptors) that exist in cells in the periodontal tissues and in infiltrated leukocytes. Existing studies point to the importance of a large number of cytokines in initiating and regulating immune responses in periodontitis, as well as in tissue destruction, by mainly activating the matrix metalloproteinases (MMP) [39; 40]. Saliva contains many antibacterial factors [41; 42] such as lysozyme, lactoferrin, and he peroxidase system, but these do not play a significant role in protection against periodontal disease [43; 44]. Initially, the liquid gingival works by washing non-stick biofilm bacteria and reduces the diffusion of bacterial metabolites to tissues by diluting them [45; 46]. The complement in the gingival fluid is activated by opsonized bacteria, their metabolic products, and by the bacterial endotoxins released [47]. The activated complement can cause lysis or inhibition of a number of bacteria and is involved in bacterial phagocytosis by neutrophils and macrophages. It can also participate in cellular distinctions through its C3a and C5a components, causing the release of histamine from mast cells, as well as other chemotactic factors and several cytokines from periodontal tissue [48].