# Electronic Cigarettes' Toxicity: From Periodontal Disease to Oral Cancer
## 2 Effects of Electronic Cigarettes on the Oral Cavity
It is a well-known fact that cigarette smoking is a major factor for the alteration of the eubiotic balance, and there is also evidence that vaping can affect the profile of the oral microbiome, although the studies on this issue are still scarce. Dysbiosis can be characterized by the alteration of microbial diversity, with the loss of beneficial microorganisms, and excessive proliferation of the pathogenic microbes. This unbalance can reduce the host's ability to fight pathogens and increase the susceptibility to infections, and to carcinogenic compounds [4; 16; 17]. In consequence, dysbiosis is associated with the initiation and progression of various oral diseases (dental caries, halitosis, periodontitis, and oral cancer) [16; 18]. Tissue damage, as a result of vaping, cannot only affect the integrity of gingival tissue but can also potentiate inflammatory responses, as well as setting up an optimal environment for bacterial growth. [PERSON] et al. investigated the effects of electronic cigarette aerosols on the human salivary microbiome and found that e-vapors exposure was linked to a higher abundance of periodontal pathogens. The proliferation of _Veillonella_ and _Porphromonas_ was significantly higher in e-cigarette users, in comparison with conventional smokers and nonsmokers, and it was accompanied by high levels of proinflammatory cytokines [19]. [PERSON] et al. revealed that the changes that appeared in the microbiome and the differences in bacterial biofilm production and architecture are more likely to be caused by the glycerol and propylene glycol present in e-liquids and not by nicotine. These sugar alcohols can become a source of nutrients for bacteria. They also discovered high virulence signatures, and proinflammatory signals in clinically healthy e-cigarette users, and they emphasize the fact that pathogenic mechanisms associated with e-cigarette use might be different from conventional cigarettes [20]. Oral microbiome alterations can be linked to the appearance of periodontitis and even oral cancer. Periodontal pathogens (_S. anginosus, C. gingivalis, P. melaninogenica, F. nucleatum_) determine an increase in markers of systemic inflammation including C-reactive protein, interleukin (IL)-1, IL-6, TNF-alpha, and MMPs, which may lead to carcinogenesis [21; 22]. _P. gingivalis, T. denticola,_ and _F. nucleatum_ promoted oral cancer migration and aggressivity. Therefore, the concepts of periodontal pathogen-mediated carcinogenesis, as well as antimicrobial-based cancer therapy have emerged [16; 17; 18]. Furthermore, due to the direct interaction with the carcinogens from cigarette smoke and e-vapors, and to the fact that oral epithelium possesses xenobiotic enzymes capable of converting proximate carcinogens to reactive metabolites, this tissue becomes a major target for smoking/vaping-associated cancer [23]. Oral cancer susceptibility is modulated by environmental factors and genetic alterations in oncogenes and tumor suppressor genes [24], and the mechanisms involved in the prevalence and progression of oral cancer are complex. A better understanding of this process can help scientists develop targeted therapies, maximize the efficiency of current drugs, but it can also have an impact on increasing awareness in the general population, thus reducing exposure to potential risk factors. Potential Mechanisms Involved in Oral Cancer Development Associated with Electronic Cigarette Smoking  
Usually, different forms of cancers share an etiology of oxidative stress associated with inflammation, DNA damage, and disrupted immune processes. Accumulation of mutations in genes encoding homeostatic regulators of DNA mismatch-repair factors, predominantly in stem cells becoming CSCs (cancer stem cells) is the leading event in carcinogenesis. The immune system and inflammatory reactions are activated when pathogens or other non-self-molecules enter an organism.