J. Penhallow et al., P53 ALTERATIONS AND HPV INFECTIONS ARE COMMON IN ORAL SCC - P53 GENE-MUTATIONS CORRELATE WITH THE ABSENCE OF HPV 16-E6 DNA, International journal of oncology, 12(1), 1998, pp. 59-68
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.