Hepatitis B virus (HBV) DNA is present as both cccDNA and integrated forms in kidney tissues of HBV surface antigen-negative patients with renal cell carcinoma

Objectives This prospective study aimed to (1) determine the intrarenal prevalence of hepatitis B virus (HBV) DNA in HBV surface antigen (HBsAg) negative patients with renal cell carcinoma (RCC), and (2) characterize its molecular forms, including cccDNA and integrated sequences. Methods Renal tissues from 83 consecutive HBsAg-negative patients who underwent nephrectomy for RCC ( n = 54) or for nonmalignant disease (control group, n = 29) were tested by highly sensitive PCR for total HBV DNA, cccDNA, and viral RNA, and subjected to high-throughput HBV DNA integration sequencing. Among RCC cases, 36/54 had clear cell RCC (ccRCC), and 18/54 had papillary or chromophobe RCC. Results HBV DNA was detected in 35.2% (19/54) of RCC cases vs 3.4% (1/29) of controls ( P = 0.001). Among RCC subtypes, HBV DNA prevalence was 25% (9/36) in ccRCC vs 55.6% (10/18) in non-ccRCC (papillary or chromophobe) ( P = 0.03). Both cccDNA and integrated HBV sequences were present in RCC tissues harboring viral DNA. Conclusion Intrarenal presence of HBV DNA is a frequently occurring event strongly associated with RCC, suggesting a potential direct role of HBV in renal carcinogenesis.