# Electronic Cigarettes' Toxicity: From Periodontal Disease to Oral Cancer
## 2 Effects of Electronic Cigarettes on the Oral Cavity  
The oral cavity, the first system in the human body in direct contact with the vapors produced by electronic cigarettes, is very exposed to the negative effects of vaping (Figure 1). The evidence of a direct link between e-cigarettes smoking and oral diseases (periodontal disease and oral cancer) is not easily obtained, because these harmful effects can be assessed after a long period of exposure, and chronic diseases (like periodontitis and cancer) need several years until the clinical symptoms appear [1]. There are a few clinical studies addressing the direct impact of vaping on the oral cavity [4]. In one cross-sectional analysis performed by [PERSON] et al., a link between poor oral health, increased odds of permanent tooth loss and daily use of e-cigarettes was observed [5]. Additionally, electronic cigarette users reported adverse events like dry mouth, sensitive teeth, mouth ulcers [6]. Another study that is often cited as evidence for the harmful effects of vaping refers to the increase in gingival bleeding that appeared when a group of smokers switched to e-cigarettes [7]. When it comes to evaluating clinical (plaque index, bleeding on probing, probing pocket depth, clinical attachment loss) and radiographic parameters of periodontal inflammation, the evidence suggested that the risks of developing periodontal disease were lower in e-cigarette users in comparison with conventional tobacco smokers, but higher than for non-smokers [8; 9; 10]. With regard to subjectively evaluating the clinical effects of electronic cigarettes on oral health, there are a few aspects that make this task challenging. One of the most important is related to the period required by several chronic diseases to develop, as mentioned above, while the popularity of these devices started to grow only within 5 to 10 years. To have a clear image, decades might be necessary until extended epidemiological studies could precisely estimate the impact of electronic cigarettes. Furthermore, many electronic cigarette users are former conventional tobacco smokers or dual users, therefore it is difficult to distinguish between the effects of traditional and electronic cigarettes [4]. Cancer represents a leading cause of death, and its incidence and mortality are rapidly escalating worldwide. In 2020, 377,713 new cases of oral cancer were recorded globally (according to GLOBOCAN). Several of the risk factors for cancer are associated with  
Figure 1: Effects of electronic cigarettes on oral cavity. socioeconomic development and with human behavior, and epidemiological studies have reported that smoking is a major etiological factor for oral cancer [11; 12]. Oral squamous cell carcinoma (OSCC) combines several cellular and biochemical alterations, accompanied by clinical modifications, affecting the morphology and function of the epithelium of the oral mucosa. Sometimes, this is preceded by white, red, or mixed mucosal changes, known as oral potentially malignant disorders (OPMDs). In the category of OPMDs are included oral lichen planus (OLP), leukoplakia (LPK), and oral submuc fibrosis (OSF). The malignant transformation rate for OLP was 1.1-1.63%, 0.13-17.9% for LPK, and 7.6% for OSF. Habitual usage of different types of tobacco products (including smokeless tobacco) is associated with a higher risk of oral potentially malignant disorders and is an important etiological factor for oral cancer [13]. Periodontal disease affects the supporting tissues of the teeth and is characterized by chronic inflammation status. There is a potential link between periodontal disease and oral cancer, and one mechanism that can explain this connection is particularly the chronic inflammation status associated with periodontal disease, which can affect normal cell growth control and induce carcinogenesis. Some studies confirm a relationship between periodontal disease and oral cancer [14; 15]. Numerous microbial species colonize the oral cavity and form the oral microbiome.