For instance, nicotine has been shown to increase the aldehyde dehydrogenase (ALDH)-positive CSC population in human breast cancer via a Notch-dependent pathway.31 Furthermore, recent studies have demonstrated that the proinflammatory cytokines TGFβ and TNFα generate CSCs in human cancer.32–34 In the present study, we investigated the effect of chronic inflammation on HPV-associated oral carcinogenesis by treating HPV-immortalized and non-tumourigenic human oral keratinocytes with TNFα for extended periods and studied the phenotypic and molecular biological changes. This evidence concerns the gene TNF and cancer.