From Chronic Inflammation to Malignancy: Molecular Mechanisms and Therapeutic Insights in Oral Carcinogenesis

Oral squamous cell carcinoma (OSCC) frequently develops within chronically injured oral mucosa and may be preceded by clinically recognizable oral potentially malignant disorders (OPMDs), which provide an important window for cancer interception. This review examines how etiological exposures, persistent inflammation, and lesion-specific epithelial–stromal–immune interactions cooperate during the transition from mucosal injury to dysplasia, carcinoma in situ, and invasive OSCC. Major carcinogenic exposures, including tobacco, alcohol, and areca nut, are considered together with context-dependent contributors such as microbial dysbiosis, viral infection, and immune-mediated epithelial injury. At the molecular level, inflammation-driven oral carcinogenesis involves cytokine and chemokine amplification, oxidative and nitrosative stress, NF-κB and STAT3 activation, the COX-2/PGE2 axis, genomic instability, field cancerization, epithelial–stromal crosstalk, angiogenesis, immune dysregulation, and epigenetic and non-coding RNA-mediated reprogramming. Emerging tools such as molecular risk assessment, liquid biopsy, optical imaging, spatially resolved profiling, and artificial intelligence-assisted models may improve identification of high-risk lesions, although most biomarkers require further prospective validation. Prevention should therefore integrate exposure control, biopsy-based diagnosis, local treatment when indicated, long-term surveillance, and trial-based precision strategies according to lesion risk, intervention window, and safety profile. This review supports a shift from lesion-centered management toward risk-adapted precision prevention in inflammation-driven oral carcinogenesis.