High frequency of p53 abnormality in laryngeal cancers of heavy smokers and its relation to human papillomavirus infection.

A series of 41 laryngeal squamous cell carcinomas was examined for p53 abnormalities and human papillomavirus (HPV) infection by an immunohistochemical and/or molecular approach. Immunohistochemically, p53 over-expression was observed in about 60% of the cancers, of which 12 were revealed to contain point mutations of p53 by a combination of the single-strand conformational polymorphism technique and direct sequencing. The p53 point mutations ranged from codons 157 to 278 and most of these mutations lay in two "hot spots" (codon 157 in four cancers and codon 248 in three cancers). The majority of p53 mutations, both transversions (seven cancers) and transitions (five cancers), occurred at the G nucleotide of the codons. An analysis of the clinical information indicated that p53 point mutation was frequently observed in heavy smokers with an average Brinkman index score of more than 1000. On the other hand, HPV DNA, type 16 or 18, was detected in a quarter of the laryngeal cancers. Of eleven HPV-positive cases, nine were immunohistochemically positive for p53, of which four contained a p53 point mutation. These results suggested no inverse relation between p53 mutation and HPV infection in laryngeal cancers. Our study indicates that p53 abnormalities are related to smoking history and the correlation might be better for smoking and chemical mutagenesis than for HPV.