Koos Boeve

21 General introduction and scope of this thesis Residual tumour cells are isolated cells after treatment of the first primary tumour which have the potential to develop as local recurrence. Field cancerization is the presence of precancerous epithelium with or without clinical manifestation (Figure 6) [42]. In general, DNA of epithelial cells undergoes several changes before they turn into a malignant tumour cell [42]. First, a stem cell in the basal layer of the epithelium will undergo (epi)genetic alterations and change into a preneoplastic stem cell. After proliferation this preneoplastic stem cell might cause a preneoplastic field of oral epithelium [72]. The ongoing exposure to the etiological factor (e.g. tobacco smoke, alcohol and betel nuts) might encounter secondary DNA alterations and turn one of these preneoplastic cells into a neoplastic cell and finally into a tumour with invasive growth surrounded by a field of preneoplastic cells (Figure 6) [42]. Because most etiological factors affects the total mucosa of the oral cavity, field cancerization is not restricted to the area of the first primary tumour and second primaries could arise from such other fields located in the oral cavity as well as in other locations of the upper aerodigestive tract (Figure 6) [42]. Figure 6. Field cancerization and residual tumour cells. Schematic model of the mucosa of OSCC cases with the different causes for local recurrences and second primary tumours as a result of field cancerization and residual tumour cells. [Source: Leemans CR, Braakhuis BJ, Brakenhoff RH, Nat Rev Cancer, 2011 [42], with permission].