Telomerase, p53 and human papillomavirus infection in the uterine cervix

Human papillomavirus infection is postulated to be a major risk factor for cervical cancer, while more recent data have stressed the clinical signific ance of telomerase expression during tumorigenesis. This study therefore lo oked for any relationship between telomerase expression, presence of human papillomavirus (HPV) and expression of the high-risk HPV E6 protein at vari ous phases of tumor progression in the uterine cervix. In addition, accumul ation of the p53 protein and total tissue proliferative fraction were also studied. Telomerase was detected using a modified TRAP (telomerase repeat a mplification protocol) assay. Expression of p53, Ki 67 and E6 protein was e valuated by immunocytochemistry. Presence of mutant p53 was detected using a mutant-specific ELISA. Type of HPV infection was determined by polymerase chain reaction and Southern blot using type-specific primers and probes. T here was a significant correlation between the expression of telomerase wit h histological grade (r = 0.646, p = 0.00003). Fisher's exact test analysis revealed that the odds ratio of a tissue sample expressing telomerase bein g a case (high-grade squamous intraepithelial lesion or invasive cancer) wa s 28.93 (p = 0.0001, 95% CI: 7.22, to 115.94). High-risk HPV-infected tissu es and those expressing E6 showed increased telomerase expression (r = 0.55 5, p = 0.00001). Similarly, accumulation of p53 protein and increased cell proliferation (Ki 67 index) also correlated to the presence of telomerase ( r = 0.661, p = 0.000004 for p53 and r = 0.647. p = 0.000003 for Ki 67). The re was no correlation between telomerase expression and presence of p53 mut ation. Activation of telomerase thus appears to be associated with high-ris k-HPV infection, accumulation of inactive p53 protein and increased cell pr oliferation in cervical lesions.