## 4 Discussion  
The present review explored vaping and heat-related products concerning oral health, investigating the comprehensive effects of ENDS and HTP on different clinical and cellular variables and offering an overview of the current literature through observational, interventional, and laboratory studies. Other recent reviews [42; 116; 117] have focused only on periodontal parameters and revealed data consistent with those reported in the present study, underlying that the results must be considered with caution because of the heterogeneity of the articles and the scarcity of RCTs. The cross-sectional studies based on surveys highlighted that the responders often need to be aware of the potentially harmful effects of alternative tobacco products [36; 42; 45; 59]. This outcome underlines need for dental professionals to provide complete smoking counseling, which should become a routine practice. Nevertheless, these surveys were judged as having a high-moderate risk of bias. While the national surveys could investigate the younger population, the same cannot be said for clinical examinations, in which mainly adults were evaluated. In regards to waterpipe (the term includes narghile, hookah, shisha, and hubble-bubble) smokers, similar detrimental effects on oral health as to those noted for ENDS were found [31]. This last category seems quite challenging to study, as waterpipes are often used in social contexts, and daily use is rare, even if a substantial use, especially in Saudia Arabia, is reported [31]. Dual smokers and former smokers were studied only in observational studies, but no clear conclusions could be made regarding these categories, as the definition of how long a subject is considered a dual smoker or how much time should pass before being labeled as a former smoker are not uniform among studies. Few studies have been found dealing with HTP and oral health; this could have a country-specific explanation, as HTP is more widespread in Japan and the USA, but less so in Europe, where its use has recently increased [116]. Another finding of the review is that there is ah variability observed in laboratory studies: different results, cell lines, bacterial strains, and oral cancer cells were considered. In any case, most of the cell line studies focused on human gingival fibroblasts, showing that e-liquids increased apoptosis and the appearance of necrosis biomarkers compared with those in unexposed cells [95; 96; 103]. Studies based on bacterial strains focused on commensal oral streptococci such as _S. mutans_[75; 94]. It has been found that flavored e-liquids are often sweeeter and stickier than unflavored ones, promoting bacterial adhesion and reducing normal commensal flora, with dysbiosis of the oral microbiome [82; 83; 94]. Regarding studies on oral cancer cells [108], conclusive hypotheses could not be drawn, since some papers suggested that ENDS and HTP might be possible alternatives to cigarette smoking. In contrast, other studies concluded that its effects are similar to those of conventional smoking [109; 110; 111]. Figure 4: Apoptosis of human gingival fibroblasts after 24 h exposure to EC versus no exposure [72; 95; 97; 105]. The risk of bias assessment resulted in low risk. At the same time, the meta-analysis, although conducted on only a few studies, confirmed that electronic cigarette smoking may have a detrimental role for oral commensal bacteria. A major limitation of this systematic review is the high heterogeneity among the studies, reflecting the lack of standardized study designs. Most studies compare ENDS or HTP with traditional cigarettes to determine whether vaping is safer/less harmful for oral health than is cigarette smoking [30; 32; 33; 40; 41; 57; 63]. However, the comparisons are often simplistic and the conclusions uncertain, as the content of e-liquids (nicotine percentage, flavorings, etc.) is profoundly different from that of conventional cigarettes.