Defining the frequency of human papillomavirus and polyomavirus infection in urothelial bladder tumours

Abstract

Given the contradictory nature of the literature regarding the role of human papillomaviruses and polyomaviruses in the pathogenesis of urothelial bladder cancer (UBC), we sought to investigate the frequency of their involvement in a large cohort of primary UBCs. DNA was extracted from 689 fresh-frozen UBC tissues and screened for the presence of high-risk human papillomavirus (HPV) types 16 and 18 and BKV/JCV genomic DNA by qPCR. In positive cases, viral identity was confirmed by Sanger sequencing and viral gene expression was analysed by RT-PCR or immunohistochemistry. All 689 UBCs were negative for HPV18. One UBC from a female patient with areas of squamous differentiation was positive for HPV16. The qPCR data indicated variable levels of polyomavirus in 49 UBCs. In the UBCs with low Cts we were able to confirm that 23 were BKV and 6 were JCV by Sanger sequencing. Polyomavirus large T antigen expression was low but detectable in 70% of the sequencing-confirmed polyomavirus positive samples. Thus, in United Kingdom patients, the presence of HPV DNA sequences is extremely rare in UBC (<1% of cases). Polyomavirus DNA (predominantly BKV) is more common in UBC, but still only detectable in 7% of cases and in many of these cases at low copy number. We have performed the largest virus screening to date in UBC, finding that HPV16, HPV18 and HPyV are unlikely to be common causative agents in UBC.

High-grade urothelial carcinoma in a kidney transplant recipient after JC virus nephropathy: The first evidence of JC virus as a potential oncovirus in bladder cancer

“…In nonimmunocompromised patients, JCV DNA sequences have been detected in several human malignancies, including brain, colon, prostate, esophageal, and urothelial bladder tumors …”

“…In nonimmunocompromised patients, JCV DNA sequences have been detected in several human malignancies, including brain, colon, prostate, esophageal, 13 and urothelial bladder tumors. 14 In addition, as JCV persists in the kidney and urinary tract after the initial infection, 1 urinary tract cells are at risk for the oncogenic effects of this virus.…”

Human Papillomavirus (HPV) Infection in Males: A Need for More Awareness

“…Other malignancies associated with HPV include SCC of the skin/nose tip and skin appendages [58][59][60][61][62]. Association between HPV and bladder cancer even though without uniform conclusions has also been reported in several studies [63][64][65][66][67][68][69].…”

Pathogenicity of BK virus on the urinary system

“…Other BKV pro-oncogenic mechanisms are also proposed and include induction of telomerase activity, deregulation of multiple crucial signalling pathways for proliferation (phosphoinositide-3 kinase-Akt/ protein kinase B, Wnt, and Ras/Raf/mitogen-activated kinase signalling pathways, STAT3, Notch, and hepatocyte growth factor receptor signalling pathway), and finally, induction vascular endothelial growth factor expression [98,[102][103][104][105] The majority of reports regarding association of urothelial cancer (both bladder and upper urinary tract) and BKV infection are case reports of immunocompromised patients [106][107][108][109]. It has to be emphasised that almost all of the described tumours are highgrade, highly aggressive with morphological features resembling the bladder cancers of SV40 transgenic mice (developed by the pathway of p53 and pRb inactivation) [98,110,111]. In a recent populationbased study on 55 697 transplant recipients, the risk of bladder tumours was found to be 1.7-fold higher in patients treated for presumed BKV nephropathy compared with transplant recipients without prior BKV infection [112].…”