REVIEW ARTICLE Genetic instability and oral cancer

Development of oral cancer proceeds through discrete molecular genetic changes that are acquired from the loss of genomic integrity after continued exposure to environmental risk factors. Of particular importance in oral cancer development are tobacco-related chemical carcinogens and human papillomavirus (HPV) infection. To understand the mechanisms by which these risk factors contribute to tumorigenesis, we developed an in vitro model of sequential, multistep oral carcinogenesis model of normal human oral keratinocytes (NHOK) by immortalizing these cells with cloned "high risk " HPV genome. HPV viral genome alone failed to give rise to a tumorigenic cell population, which required further exposure to chemical carcinogens. HPV-immortalized cells exhibite