HPV DNA AND P53 ALTERATIONS IN OROPHARYNGEAL CARCINOMAS

We have examined a series of 37 oropharyngeal squamous cell carcinomas for the presence of HPV 6/11, 16, and 18 DNA by polymerase chain reac tion (PCR)/Southern blotting and for p53 alterations by immunohistoche mistry and mutation screening with temperature gradient gel electropho resis (TGGE). HPV sequences were found in a total of 26 of 37 cancers (70.3%), most frequently HPV 16 (20/37) followed by HPV 18 (11/37). Do uble infections with HPV 16 and 18 were present in 5 tumours. p53 accu mulation was detectable immunohistochemically in 21 of 37 carcinomas ( 56.8%). There were remarkable differences in the distribution of immun oreactive tumour cells in relation to the tumour grade. A mutation scr eening for p53 by TGGE, directed to the amplified exons 5-8, revealed p53 mutations in 14 of 37 carcinomas (37.8%). Mutations in two differe nt exons were present in 3 tumours, 11 tumours being hit once. Exon 7 was mutated in 6 carcinomas, exons 5 and 8 in 4 cases, and exon 6 in 3 cases. When grouping the tumours with p53 mutation according to their HPV state, HPV-positive cases showed slightly more mutations (11/26) than HPV-negative cases (3/11). Only 5 of 37 carcinomas (13.5%) contai ned neither HPV DNA nor p53 alterations. Our results indicate that hig h-risk HPV and p53 mutations frequently coexist in oropharyngeal carci nomas, in contrast to genital tumours, notably carcinomas of the cervi x uteri. This may reflect different pathways in carcinogenesis in squa mous cell epithelium from different sites.