# The Link between Periodontal Disease and Oral Cancer--A Certainty or a Never-Ending Dilemma?
## 4 Periodontal Disease and Oral Cancer
### The Link between Periodontal Disease and Oral Cancer-Current Vision  
Poor oral hygiene [92], poor dentition, periodontal disease [93], and missing teeth or denture use [94] have all been proposed as risk factors from the earliest case-control studies on oral cancer [95,96]. The main challenge with cancer, as with heart disease, is determining whether or not the connections are causal. Prospective cohort studies with extensive follow-ups can begin to address causality since exposure is determined many years before cancer diagnosis. [PERSON] et al. [97] proved that tobacco and alcohol use contribute significantly to the risk of developing oral cancer. There were no significant differences between the risk estimates for the two genders or young and old persons. [PERSON] et al. indicated that there is an association between cancer and more severe periodontal disease regardless of oral hygiene and dental health status [98]. [PERSON] et al. noted that periodontal disease (as indicated by poor condition of the mouth and missing teeth) and daily mouthwash use may be independent causes of cancers [99]. [PERSON] et al. showed a significant positive association between tooth loss and the risk of head and neck cancers after adjustment for potential confounding factors [100]. The findings indicate that preventive efforts aimed at the preservation of teeth may decrease the risk of these cancers. Oral squamous cell carcinomas are among the most common cancers in southeast Asia, and more so in the Indian subcontinent. [PERSON] et al. found that _P. gingivalis_, one of the most common bacteria responsible for acute periodontitis, has been linked to the invasion and spread of highly invasive oral cavity malignancies [101]. By activating promatrix metalloproteinases [102,103], as well as anergy and death of activated T cells [94,104], _P. gingivalis_ aids in cancer growth and metastasis. Squamous cell carcinoma is prevalent in northeastern Iran, with one of the highest incidences in the world. [PERSON] et al. concluded, in agreement with two other previous studies, that poor oral health and periodontal disease are risk factors for squamous cell carcinoma [105]. [PERSON] et al. proved that periodontal disease was associated with a small, but significant, increase in overall cancer risk, which persisted in non-smokers [12]. Bacteria found in the mouth are quite complex. The significance of the oral microbiota in in-situ or distant tumor growth has gotten a lot of attention. Following investigations, the global risk of malignancies caused by microbial infections was estimated to be 16.1%, emphasizing the importance of the microbiota [106]. These findings have thrown light on continuing research in the field, reinforcing the view that oral microbiota might play a significant role in cancer through many ways, and that a complete understanding of these mechanisms can aid in tumor resistance. Figure 2: Schematic representation of potential processes involved in the periodontal disease–oral cancer connection. Carcinogenesis has been linked to a large range of oral microorganisms. _F. nucleatum_ and _P. gingivalis_ are two such that have been linked to the progression of different cancers. Bioinformatic prediction analysis of sequencing data revealed a high abundance of the _F. nucleatum_ subspecies _Polymorphum_ in oral cancer tissues during in situ oral squamous cell carcinoma [107]. _F. nucleatum_ was found in squamous cell carcinoma when quantitative polymerase chain reaction (qPCR) was used to determine its DNA content [108]. The relative abundance of _F. nucleatum_ had a negative connection with cancer-specific survival, implying that _F. nucleatum_ is only a predictive biomarker. _P. gingivalis_ has lately been thought to have a role in the development of cancers due to its ability to disrupt epithelial tissues and host defense mechanisms [109]. Since the oro-digestive tract is a continuous smooth tube, _P.