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

BACKGROUND. It has been suggested that the p53 tumor suppressor gene regula tes 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. METHODS. Fifty-two patients with International Federation of Gynecology and Obstetrics Stage IIIB squamous cell carcinoma of the cervix who received r adiation therapy alone were reviewed. The combination of external beam irra diation therapy and three sessions of intracavity brachytherapy irradiation was performed for all patients. Genomic DNA extracted from paraffin embedd ed tissues was examined for HPV types 16, 18 and 33 by the polymerase chain reaction (PCR) method and for p53 status by PCB-single-strand conformation polymorphism (PCR-SSCP) technique. The effects of HPV infection, p53 statu s, and other parameters on clinical outcome were investigated by univariate analysis. RESULTS. 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 corr elation 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 recur rent tumors, whereas p53 were wild type in 32 of 40 patients (80%) who achi eved local control. The p53 mutation had a significant correlations with lo cal tumor recurrence, Furthermore, p53 status caused statistical significan t 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, res pectively). Conversely, no obvious correlation with any clinical outcome fo r patients with cervical carcinoma was found concerning HPV infection. CONCLUSIONS. It is possible that the p53 gene may be used as a predictive f actor in radiation therapy for patients with Stage IIIB squamous cell carci noma of the cervix.