We studied 51 cervical carcinomas, among them 25 squamous-cell carcinomas (SCC) and 26 cervical adenocarcinomas (AdCa), and 40 vulvar SCC for the presence of HPV and mutant p53. HPV was detected by PCR, and p53 alterations by temperature-gradient gel electrophoresis/direct sequencing and immunohistochemistry. HPV, mostly type 16/18, was found in 80.4% of the cervical tumors (92.0% of the SCC and 69.2% of the AdCa), but in only 27.5% of vulvar carcinomas. In contrast, p53 mutations were found in 7.8% and 52.5% of cervical and vulvar tumors respectively. Mutant p53 occurred in pre-invasive vulvar lesions, indicating that this oncogenic factor is involved early in carcinogenesis. Further analysis of recurrent/metastatic lesions of 9 cervical and 14 vulvar tumors also showed remarkable differences: in cervical cancer, HPV was persistent, and p53 mutations absent, whereas in vulvar tumors, HPV was mostly absent or not persistent, and the p53 mutation rate was very high (78.6%). These observations suggest that HPV persistence is an important event for the evolution and maintenance of cervical cancer, whereas for vulvar cancers p53 mutation and not HPV activity is a central oncogenic event.

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.

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