# The Link between Periodontal Disease and Oral Cancer--A Certainty or a Never-Ending Dilemma?
## 4 Periodontal Disease and Oral Cancer
### Hypotheses for Etiology of a Link between Periodontal Disease and Oral Cancer  
Periodontal disease can be a symptom of an underlying immune system problem or a direct cause of cancer [60]. Periodontal disease may potentially be a good indicator of a vulnerable immune system, or it may directly influence cancer risk due to inflammatory loading [84; 85]. There are several probable explanations for the relationship between periodontitis and cancer.  
The oral microbiota is crucial to the human microbiome and the body's overall health, and oral and systemic illnesses, as well as chronic inflammation, can result from microbial imbalances with their hosts [86]. Periodontal pathogens can cause chronic inflammation, which promotes already begun cells and results in a breakdown of normal cell growth control and the possibility of carcinogenesis.  
Oral cancer progression has been shown to be aided by direct contacts with oral epithelial cells by _Fusobacterium nucleatum (F. nucleatum)_, a known pathogenic oral species that demonstrated a 5.88 % increase in cancer lesions [87]. [PERSON] et al. demonstrated that in cancer lesions there were ten species that had significantly higher abundances [88]. These species included _Fusobacterium nucleatum, Prevotella intermedia, Aggregatibacter sepsis, Peptostreptococcus stomatis_ and _Catonella morbi_, all of which live in the oral mucosa as commensals but can became opportunistic in certain situations related to oral cancer.  
Many viruses, like human cytomegalovirus and the carcinogenic Epstein-Barr virus, have been found in periodontal diseases and are considered to be linked to cancer, including lymphoma and nasopharyngeal carcinoma. There's also some indication that certain strains of candidiasis are more common in oral cancer patients [89].  
Chronic periodontal disease can indicate that a person's immune system is unable to eliminate infection and, as a result, is unable to detect tumor progression.  
Periodontitis could be a sign of a certain sort of immune function that influences tumor growth and progression.  
Chronic periodontal inflammation has been shown to induce genetic damage by the generation of oxidizing chemicals, like reactive oxygen and nitrogen species, which have been linked to an increased cancer risk.  
Pro-inflammatory plasma cytokines, peripheral white blood cells, prostanoids, proteases--including matrix metalloproteinases--and acute-phase proteins are examples of inflammatory indicators produced in the immunological response to periodontal disease [90].  
Another potential explanation for the reported findings is the increased formation of carcinogenic nitrosamines. Poor oral hygiene, periodontal disease, cigarette use, and certain dietary variables all stimulate the generation of endogenous nitrosamines in the oral cavity by nitrate-reducing bacteria [91].  
Essential mechanisms that control the periodontal inflammatory response fail.  
In the 19 th century, [PERSON] was the first to suggest a relationship between inflammation and cancer. He observed leukocyte infiltration in the tumor microenvironment and hypothesized that persistent inflammation may be a factor in cancer progression [79].  
Figure 2 summarizes all the above hypotheses [79; 86; 87; 88; 89; 90; 91].