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.