P53 ALTERATIONS AND HPV INFECTIONS ARE COMMON IN ORAL SCC - P53 GENE-MUTATIONS CORRELATE WITH THE ABSENCE OF HPV 16-E6 DNA

To examine the association between HPV infections and p53 gene aberrat ions, a panel of 28 oral squamous cell carcinomas (SCC) and 12 potenti ally malignant oral mucosal lesions were analysed for p53 mutations in exons 2-9. p53 protein was analysed by immunocytochemistry using DO7 antibody. The same panel was also examined for the possible presence o f HPV infection. p53 overexpression was detected in 13/26 (50%) malign ant and 2/9 (22%) premalignant lesions. Mutations in the coding region of the p53 gene were found in 10 malignant samples. None of the prema lignant lesions were shown to have p53 mutations. The total number of p53 mutations in 10 samples were 14 of which 12 (85%) were in exon 5 s uggesting the presence of hot spots in exon 5 for carcinogens involved in the transformation of oral epithelial cells. The presence of HPV D NA was first screened with consensus primers to the L1 region and nest ed PCR approach. HPV 6 and HPV 16 were detected in 14/28 (50%) oral SC C and 4 of 12 (33%) precancerous lesions, 7 tumours harboured both typ es. The samples were then examined for the presence of E6 oncogenic se quence of HPV16 using E6 specific primers. 7/27 (26%) SCC and 5/9 (55% ) premalignant lesions harboured E6 DNA of which 6 (3 SCC and 3 premal ignant) were negative with L1 primers suggesting possible integration of the specific viral genes or loss of other viral DNA sequences after integration of larger viral fragments. 9/10 (90%) SCC with p53 mutati ons were negative for E6 DNA. Our results show that both p53 alteratio ns and HPV infection may be important etiological factors in the devel opment of oral cancer. However, there is: i) No concordance between p5 3 mutations and its overexpression. ii) the presence of HPV capsid DNA (L1) does not necessarily indicate the presence of HPV oncogenic gene s. iii) p53 gene mutations, but not overexpression, correlate with the absence of HPV 16-E6 and not L1 gene.