Reviewing the oral carcinogenic potential of E-cigarettes using the Bradford Hill criteria of causation

The past decade has seen a surge in the use of e-cigarettes, which has prompted the medical community to assess any associated potential health hazards. A major concern was the risk of cancer. Chemical analysis of e-cigarettes has shown the presence of volatile organic compounds with the potential for carcinogenicity. Comparative toxicology analysis has shown e-cigarette to have relatively lower dosages of toxins than conventional combustible cigarettes. Based on comparative analysis, e-cigarettes have been increasingly advocated as a safe alternative to conventional cigarettes. It is vital to recognize that presence of relatively lower toxin level does not preclude carcinogenic potential. The nicotine present in the e-cigarette was presumed to be the major cytotoxic agents, thus nicotine-free e-cigarette was considered as inert. On the contrary, experimental studies on oral cell lines have shown DNA strand breaks on exposure to e-cigarette vapors with or without nicotine. In addition, dysregulations of genes associated with carcinogenic pathways have also been demonstrated in oral tissues exposed to e-cigarette vapors. Despite alarming molecular data, the oral carcinogenic potential of e-cigarette remains unclear, which can be attributed to the lack of long-term prospective and large-scale case-control studies. As e-cigarette users often have other well-established risk factors (conventional cigarette smoking, alcohol, etc.) as associated habits, it is difficult to assess e-cigarette as an independent risk factor for oral cancer. Thus, the present manuscript aims to review the published literature using the Brad Ford Hill criteria of causation to determine the oral carcinogenic potential of e-cigarettes.