Nicotine pouches, oral cancer and tobacco harm reduction: current evidence and research priorities

Tobacco smoking remains the most consistent and preventable risk factor for oral cancer, driven by exposure to combustion-derived toxins that promote DNA damage, inflammation and microbiota dysregulation. Global data show substantial geographic variability in disease burden, with particularly high incidence and mortality especially in South and Southeast Asia, where culturally reinforced and deeply embedded forms of high-nitrosamine smokeless tobacco and areca nut continue to drive risk. In this evolving landscape, nicotine pouches have rapidly expanded as tobacco-free oral products manufactured to deliver nicotine without combustion. Toxicological analyses reveal significantly lower levels of harmful constituents relative to cigarettes and traditional smokeless tobacco, and short-term clinical studies report reductions in oral mucosal irritation and gingival inflammation among exclusive users. However, no long-term epidemiological evidence is currently available to assess their potential impact upon oral carcinogenesis, and existing human studies remain few, small and heterogeneous. This mini review highlights critical priorities for research, including the need for long-term prospective studies, standardized product testing, independent toxicological assessments and surveillance of patterns of use, dual use and youth uptake. The integration of harm reduction approaches with established prevention strategies may offer opportunities to mitigate oral cancer risk in adults who smoke and/or consume unregulated smokeless tobacco products with high risk profiles that are very common in Asia, the Middle East and Africa. However, this approach requires cautious interpretation of the current evidence and ongoing monitoring of emerging products.