Human papilloma virus DNA and p53 mutation analysis on bladder washes in relation to clinical outcome of bladder cancer.
OBJECTIVE
High-risk human papilloma virus (HPV) types stimulate degradation and deactivation of protein associated with the p53 tumour suppressor gene via the ubiquitin-dependent pathway. For a long time, changes of the p53 tumour suppressor gene have been correlated with poor clinical outcome in patients with superficial bladder cancer. We aimed to study the association between presence of (high-risk) HPV DNA, p53 status, and clinical outcome in bladder cancer patients. This study must be seen as a preliminary study to investigate this potentially important problem.


METHODS
From 107 patients, 166 bladder wash samples were obtained. p53 status was determined by mutation analysis, HPV detection, and genotyping by the SPF(10)-LiPA assay. Clinical data were abstracted from the medical files.


RESULTS
The prevalence of all-type and high-risk HPV infection in malignancies of the bladder was 15.2% and 8.1%, respectively. In high-grade tumours this prevalence was 18.2% and 10.6%, respectively. In grade 1, 2 and 3 tumours the infection rate of high-risk HPV types was 0%, 3.3%, and 10.6%, respectively (trend test: p=0.221). In Ta, T1, and T2-T4 tumours the high-risk HPV infection rate was 0%, 12.5% and 18.2%, respectively (trend test: p=0.045). In the p53 wild-type patients who showed progression, 1 of 9 patients had a high-risk type HPV infection. In the group of wild-type patients who showed no progression, 4 of 37 patients had a high-risk type HPV infection (odds ratio: 1.03; 95% confidence interval, 0.1-10.5).


CONCLUSIONS
The data of this pilot study show the suggestion of a positive trend in the correlation between tumour grade/stage and high-risk type HPV infection. However, no additional risk for progression is found for p53 wild-type patients with a high-risk HPV infection.
Moonen
Paula M J
PM
Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Bakkers
Judith M J E
JM
Kiemeney
Lambertus A L M
LA
Schalken
Jack A
JA
Melchers
Willem J G
WJ
Witjes
J Alfred
JA
D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis*; D016158:Genes, p53; D005838:Genotype; D006801:Humans; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014412:Tumor Virus Infections / Q000150:complications; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000821:virology*
D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53