We analyzed specimens of head and neck squamous cell carcinomas (HNSCC) from 110 patients for p53 gene mutations, and 92 of them for human papillomavirus (HPV) infection, in order to evaluate the prognostic significance of these factors by comparison with clinical follow-up data. Mutations within the exons 5 to 8 of the p53 gene were found in 48 tumors (44%). Sequencing revealed in most cases mis-sense mutations (16/21). Frequency of p53 gene mutations was not related to the tumor stage or the presence of lymph node metastases. Of the 46 tumors that were analyzed by immunohistochemistry, 26 stained positively (56%). The number of positively stained nuclei increased slightly with decreasing differentiation of the tumors, whereas no correlation was found between tumor stage and immunoreactivity. An infection with the high-risk HPV types 16 and 18 could be detected in 39/92 tumor specimens (42%). Follow-up data were obtained from 99 patients within a range of 2 to 112 months. No dependence of overall survival on the presence of p53 gene mutations or HPV infection could be observed. The absence of statistically significant correlations between p53 gene mutation and progressive disease, however, does not deny its putative relevance in early phases of tumor development.

We studied the p53 mutational spectra of 34 lip and 60 intra‐oral squamous‐cell carcinomas and examined possible etiological and prognostic correlations for these tumor sites. For the p53 analysis of exons 5–8, we used PCR/TGGE screening followed by DNA sequencing. Mutations were found in 18/34 (53%) lip and 22/60 (38%) intra‐oral carcinomas. The p53 mutational spectrum of the intra‐oral carcinomas comprised transitions and transversions in nearly equal frequency (11 to 10). In comparison, transitions were 3.5 times more frequent than transversions (14 to 4) in carcinomas of the lip. The predominant types of base change found in intra‐oral tumors were G:C‐to‐T:A transversions and G:C‐to‐A:T transitions (32% each), while in lip tumors G:C‐to‐A:T transitions (70%) were the most frequent. The rate of lip tumors with mutations was higher in non‐smokers (8/13) than in smokers (9/20). In contrast, p53 mutations in intra‐oral tumors clustered in smokers (18/47 vs. 2/10). G:C‐to‐T:A transversions, regarded as tobacco smoke–associated in lung cancer, were found in 2 moderate and 4 heavy smokers with intra‐oral cancer. This base substitution was found in none of our lip cancers. In lip tumors, a high rate of mutations occurred at dipyridine sites (13/18); among these were 8 C‐to‐T transitions and 1 CC‐to‐TT tandem base transition. These changes are characteristic of DNA damage caused by UV light. The presence of mutational events at the DNA‐binding surface of the p53 protein may correlate with poor clinical outcome. However, we could not find any statistically significant correlations between p53 status and survival. Only the recurrence‐free interval was significantly shortened in cases with mutations affecting residues of the DNA‐binding surface of the p53 protein. Int. J. Cancer 88:82–86, 2000. © 2000 Wiley‐Liss, Inc.

Mutations of the p53 gene are the most commonly observed genetic alterations in malignant tumors and are often associated with a loss of the tumor suppressor function of the p53 protein. We have analyzed specimens of head and neck squamous cell carcinomas (HNSCC) from 110 patients for p53 gene mutations and 92 of them additionally for human papillomavirus (HPV) infection in order to evaluate the prognostic significance of these factors by comparison with clinical follow-up data. Using the method of polymerase chain reaction (PCR)/temperature gradient gel electrophoresis (TGGE), mutations within the exons 5 to 8 of the p53 gene were found in 48 tumors (44%). Sequencing revealed missense mutations in most cases (15/20). Frequency of p53 gene mutations was not related to the tumor stage, the grade of differentiation, the presence of lymph node metastases, or the smoking history of the patients. With the help of a highly sensitive PCR/hybridization assay, an infection with the high-risk HPV types 16 and 18 could be detected in 39/92 tumor specimens (42%). Follow-up data were obtained from 99 patients with a range of 2-112 months. No correlation of overall survival on the presence of p53 gene mutations or HPV infection could be observed. The absence of statistically significant correlations between p53 gene mutations and progressive disease, however, does not exclude its putative relevance in early phases of tumor development.