p53 mutations in squamous cell carcinoma of the head and neck predominate in a subgroup of former and present smokers with a low frequency of genetic instability.

We examined the p53 mutational profile of 65 squamous cell carcinomas of the head and neck (SCCHNs) from patients living in northwest England. Twenty-three p53 mutations were detected in 20 samples (31%). GC-->AT transitions were the predominant type of mutation. The p53 mutational profile of SCCHN tumors was similar to that of non-small cell lung tumors from patients within the same geographical area, supporting the idea of a common model for carcinogenesis in the upper respiratory tract. Statistical analysis showed that the incidence of p53 mutations among present and former smokers was significantly higher than that in nonsmokers (P < 0.02). In addition, p53 mutations were found to predominate in a group of SCCHN patients with low genetic damage, as indicated by the fractional allelic loss value. The above findings suggest an early initiating role for p53 and imply that at least two separate carcinogenic pathways may be involved in the development of SCCHN.