The effects of p53 status and human papillomavirus infection on the clinical outcome of patients with stage IIIB cervical carcinoma treated with radiation therapy alone.

Abstract

It has been suggested that the p53 tumor suppressor gene regulates the radiosensitivity in human malignancies after irradiation; however, in cervical carcinoma, the role of the p53 gene is still unclear because of inactivation of functional p53 by infection with human papillomavirus (HPV). The objective of this study was to clarify the effects of p53 status and HPV infection on the clinical outcome of patients with cervical carcinoma after undergoing radiation therapy. Fifty-two patients with International Federation of Gynecology and Obstetrics Stage IIIB squamous cell carcinoma of the cervix who received radiation therapy alone were reviewed. The combination of external beam irradiation therapy and three sessions of intracavity brachytherapy irradiation was performed for all patients. Genomic DNA extracted from paraffin embedded tissues was examined for HPV types 16, 18 and 33 by the polymerase chain reaction (PCR) method and for p53 status by PCR-single-strand conformation polymorphism (PCR-SSCP) technique. The effects of HPV infection, p53 status, and other parameters on clinical outcome were investigated by univariate analysis. HPV-DNA was detected in 40 patients (76.9%), and 14 patients (26.9%) had mutations of the p53 gene in the study. There was a significant correlation between the existence of HPV and p53 status (P < 0.001). Mutations of the p53 gene were detected in 6 of 12 patients (50%) who had local recurrent tumors, whereas p53 were wild type in 32 of 40 patients (80%) who achieved local control. The p53 mutation had a significant correlations with local tumor recurrence. Furthermore, p53 status caused statistical significant differences in the curves of the recurrence free survival rate and local control rate as determined by the log rank test (P = 0.02 and P = 0.03, respectively). Conversely, no obvious correlation with any clinical outcome for patients with cervical carcinoma was found concerning HPV infection. It is possible that the p53 gene may be used as a predictive factor in radiation therapy for patients with Stage IIIB squamous cell carcinoma of the cervix.