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 immunohi stochemical 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 si ngle-strand conformational polymorphism technique and direct sequencin g. The p53 point mutations ranged from codons 157 to 278 and most of t hese mutations lay in two ''hot spots'' (codon 157 in four cancers and codon 248 in three cancers). The majority of p53 mutations, both tran sversions (seven cancers) and transitions (five cancers), occurred at the G nucleotide of the codons. An analysis of the clinical informatio n indicated that p53 point mutation was frequently observed in heavy s mokers 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 l aryngeal cancers. Of eleven HPV-positive cases, nine were immunohistoc hemically positive for p53, of which four contained a p53 point mutati on. These results suggested no inverse relation between p53 mutation a nd HPV infection in laryngeal cancers. Our study indicates that p53 ab normalities are related to smoking history and the correlation might b e better for smoking and chemical mutagenesis than for HPV.