JCPyV Infection is Highly Prevalent in UTUC: Implications for Oncogenic Factors and Pathological Staging

Abstract Background Upper tract urothelial carcinoma (UTUC) is a subtype of urothelial carcinoma that shares similarities with bladder cancer but is more aggressive. Human polyomaviruses (HPyVs) have been found in UTUC; however, the association of the viral large T antigen (LT) protein and the tumor suppressor protein, p53, post-infection with the clinical characteristics of UTUC remains unclear. This study aimed to investigate the prevalence of the JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) in UTUC and their correlation with cancer progression among the southwest Taiwanese population from 2020 to 2022. Methods A total of 72 paraffin-embedded UTUC tissue samples and 41 adjacent normal tissue samples were collected from 72 patients. Nested polymerase chain reaction and DNA sequencing were used to detect viral DNA and genotypes. Immunohistochemistry was used to detect the expression of early protein LT and cellular p53 protein. Results The overall prevalence of HPyVs was higher in UTUC samples than in normal tissue samples (65.3% [47/72] vs 17.1% [7/41]). Among the UTUC samples with HPyVs, JCPyV and BKPyV were detected in 62.5% (45/47) and 2.8% (2/47) of the samples, respectively. JCPyV-TW-3 was the predominant strain of JCPyV infection. In UTUC samples, the LT protein positivity rate was 65.3%, and the p53 protein was prevalent in 45.8%. JCPyV infection increased the risk of UTUC by 9.13-fold, and this increased by another 9.13-fold with LT protein expression. The risk of UTUC was higher by 7.83-fold in those with p53 expression and by 8.58-fold in those with co-expression of LT and p53. Compared with males, females had a 5.19-fold higher probability for both JCPyV infection and LT expression. The probability of LT and p53 co-expression was 4.15-fold higher in females. Patients aged ≥ 65 years had a 2.98-fold higher probability of p53 expression. In the advanced stages, the probability of virus-induced LT expression was 3.18-fold higher, and the probability of LT and p53 co-expression was 2.86-fold higher. Conclusions JCPyV infection is highly prevalent in UTUC, and the concurrent high expression of LT and p53 can be a useful biomarker for treatment and prognosis.