Human papilloma virus DNA and p53 protein expression among Egyptian patients with urinary bladder cancer in relation to schistosomiasis and clinicopathologic outcome

ABSTRACT

Several studies have demonstrated an association between human papilloma virus [HPV] infection and urological malignancies. Inactivation of p53 tumor suppressor gene is a common genetic change in human cancers. Since proper understanding of the natural history of bladder cancer and significant prognostic factors is critical for management of this disease, we aimed to study the role of HPV16, 18 types and p53 protein expression among 72 Egyptian patients with bladder cancer in relation to schistosomiasis and clinicopathological parameters. Polymerase Chain Reaction assay [PCR] was used for detection and typing of HPV-DNA in bladder tissue biopsies where as p53 protein over expression was detected by immunohistochemistry. Results revealed that 36.1% of bladder tumors were schistosomiasis-associated, while 69.4% and 78.6% were significantly related to transitional cell carcinoma [TCC] and low grade tumor respectively. HPV16, 18 DNA types were detected in 41.7%, the majority of which [66.6%] was of type-16. p53 protein expression and its coexistence with HPV DNA-types was detected in 66.7% and 38.9% of tumors respectively. Although p53 protein expression had no statistically significant relation to schistosomiasis, the presence of HPV DNA or its coexistence with p53 showed statistically significant relation. In pre-malignant lesions, positive HPV DNA incorporation and p53 expression were detected in 20% and 12.5% respectively. Fair correlation was recorded between the presence of HPV DNA-types and p53 expression [kappa coefficient = 0.421]. Significant marked expression of p53 was detected in 92.9% of HPV DNA positive cases. There was no significant association between tumor recurrence and HPV DNA positivity. It is worth mentioning that marked expression of p53 was significantly associated with recurrent tumors [85.7%]. In conclusion, both HPV infection and p53 protein expression could contribute to schistosomal bladder carcinogenesis in an independent way. Over expression of p53 could play a role as an indication for high risk HPV infection or for tumor recurrence tendency. We suggest screening of patients with schistosomiasis for high risk HPV-16 and HPV-18, as they will need more strict treatment modalities and follow up besides, monitoring of their response to therapy. Further data are needed to study the relation between HPV and the reduction in cancer-specific survival, which is the ultimate goal of screening