Figure 2 Hypothetical pathways for head and neck squamous cell carcinoma (HNSCC) development. Genetic and epigenetic alteration of p53 follows distinct pathways during the development of HNSCC from normal epithelium via leukoplakia/dysplasia. Transition from normal to leukoplakia/dysplasia is associated with the germline p53 codon 72 polymorphisms,¹⁹ whereas p53 mutation and human papilloma virus (HPV) mediated p53 inactivation are later events (transition from leukoplakia/dysplasia to HNSCC) and possibly constitute two independent pathways of tumourigenesis.