Smoking is a major public health concern that significantly impacts the oral cavity, the primary site of exposure. Tobacco consumption has been linked to conditions such as leukoplakia, oral cancer and impaired wound healing and severe periodontal disease. At the same time, vaping disrupts the oral microbiome and compromises implant stability, both influenced by social, economic, behavioral and political determinants. Evidence suggests that multicomponent interventions, including dental-based programs combined with community initiatives, behavioral strategies such as Motivational Interviewing and the 5Rs framework and pharmacotherapies such as varenicline, bupropion or NRTs are essential for improving cessation outcomes and reducing tobacco-related oral health risks. Thus, we show the consequences of conventional smoking and vaping on oral tissues, periodontal structures, sensory perception, dental implants and saliva.

Cigarette smoking is a major environmental risk factor that compromises oral mucosal immunity; however, the mechanisms underlying smoke-induced epithelial dysfunction remain poorly defined. In this study, we identify cigarette smoke-induced nuclear accumulation of caspase-12 as a previously unrecognized event associated with dysregulation of epithelial innate immune responses. Analyses of clinical oral leukoplakia tissues and an active smoking rat model revealed leukoplakia-like epithelial alterations accompanied by enhanced Candida albicans colonization, together with marked nuclear enrichment of caspase-12, NF-κB p65, and RIP2. In immortalized human oral epithelial Leuk-1 cells, exposure to cigarette smoke extract (CSE) induced a concentration-dependent increase in nuclear caspase-12, NF-κB p65, and RIP2, supporting a direct effect of cigarette smoke on epithelial immune signaling. Silencing of caspase-12 attenuated CSE-induced nuclear localization of NF-κB p65 and altered RIP2 distribution. Importantly, caspase-12 knockdown restored epithelial antimicrobial function, as evidenced by increased secretion of the antimicrobial peptides hBD1 and hBD3 and enhanced antifungal activity of epithelial culture supernatants against Candida albicans under CSE exposure. Collectively, these findings indicate that caspase-12 nuclear accumulation contributes to cigarette smoke-induced impairment of epithelial innate immunity.

Early detection of potentially malignant and malignant lesions in the oral cavity is mandatory for reduction in oral cancer incidence, detection at an early stage and improving survival. The objective of this study was to catalogue the transcriptomic pattern across pre-cancerous stages, identify the major signalling processes, and infiltrating immune cell subtypes using the integrated, multi-dataset, meta-analysis approach. Following a search in the public databases, a total of five datasets were included in the study. The patient samples were stratified to identify the changes in high-grade dysplasia (HGD, moderate/severe dysplasia) as opposed to low-risk lesions (LRL, benign/OPMD) and low-grade dysplasia (LGD). Weighted gene co-expression network analysis (WGCNA; p < 0.05, |Correlation coefficient|:0.3) integrated with differential gene expression (DEG; p < 0.05, Fold change: 1.5) analysis revealed alterations in low-to-high-risk lesions included changes in DNA replication, loss of cell adhesions converging on a hub panel of tumor promoter/suppressors. The shift to high grade dysplasia was marked by enhanced immune/cytokine signalling with hub-gene network driving metabolic regulation, immune evasion, and ECM-stroma interaction. In transformed lesions, the immune-modulatory environment persisted, now accompanied by a notable downregulation of interferon (IFN) signalling. Interferon-inducible network and stemness induction were key hub gene networks. Digital cytometric analysis indicated specific enrichment of T regulatory cells and dendritic cells in differentiating the grades of dysplasia, while T helper cells were specific for malignant transformation. Collectively, these results indicate the role of immune surveillance during oral carcinogenesis. The distinct molecular/immunological shifts during dysplastic progression and malignant transformation represent critical milestones in oral potentially malignant disorder (OPMD) progression, offering actionable insights for prognosis, prevention, and therapeutic intervention.