Squamous change in bladder cancer and its relevance to understanding clonal evolution in development of bladder cancer.

Using conventional morphological assessment, squamous change in bladder epithelium has been observed in 73% of bilharzial associated squamous cancers but only 28% of pure transitional cancers. However, more detailed studies of patients with TCC suggest that the latter figure may be an underestimate, since in one series it was reported to be more than 50%. The most significant risk factor for development of squamous carcinoma in the bladder is chronic persistent bacterial cystitis, although in the areas of the world where bilharzia is endemic this infestation also increases the risk of both squamous bladder cancer and chronic bacterial cystitis. Although it is clear that carcinogens are involved as co-factors in transformation from squamous metaplasia to cancer, the fact that in Zimbabwe one author has observed that TCC is more frequent in whites than squamous cancer is in bilharzia infected blacks is evidence that other unidentified risk factors are involved. This is increasing evidence for involvement of HPV subtypes in cervix, oropharynx and lung cancer. As all three of these tumours are associated with squamous metaplasia, there could be a case for investigation of bladder squamous tumours for HPV involvement. This is particularly so given the observation of the "hit and run" type of transient infection in cattle that develop BPV associated tumours and the tenfold difference (30% vs 3%) in frequency of HPV detection in squamous skin tumours developing in immunosuppressed individuals compared with those arising spontaneously. With new technology for cytological screening techniques using dot ELISA and evidence of differences in TP53 mutations that support the involvement of nitrous oxide, it is clear that there is more to learn from study of this tumour type that may be of general interest in understanding the clonal development of cancer.