Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review

Table 5 Characteristics of available studies, reported in English, assessing the association between hepatitis C virus infection and renal cancer

Author/Journal/Publication year	Country	Study design/study period	Diagnosis	Sample size (HCV positive RCC cases)	Control source	HCV positive controls/controls	Matching factors	Percentage of HCV-positive cases with 95%CI	Main conclusions
Amin J J Hepatol 2006	Australia	Community-based cohort-study Period: 1990-2002	Identification of renal cancer cases by means of ICD-10- diagnosis codes	Individuals with HCV infection: 75834 RCC detected: 19 19/75834	Incidence observed in the study cohort was compared to expected incidence derived from NSW population cancer rates by calculating standardised incidence ratios	SIR: 0.9 (0.6-1.4)	NR	0.02 (0.01-0.03)	No evidence supporting an association between HCV infection and kidney cancer development
Budakoğlu B Med Oncol 2012	Turkey	Case series with control group 2005-2010	Histological confirmation	15/903 (1.7%)	Data collected in previous prevalence studies in healthy subjects in three different geographical areas of the Turkey, used as control group	81/5267 (1.5%)	NR	1.7 (0.8-2.4)	No higher frequency of HCV positivity in RCC patients in comparison with healthy people
Gonzalez HC Dig Dis and Sci 2015	United States	Case series with control group January 2011 - August 2013	Histological confirmation	Anti-HCV positive: 11/140 (7.9%) (2) HCV-RNA positive: 9/140 (6.4%)	Consecutive individuals newly diagnosed with colon cancer. The control group recruited simultaneously and from the same health care system (Henry Ford Health System in Detroit, Michigan)	Anti-HCV positive: 1/100 (1%) HCV-RNA positive: 0/100	NR	(1) 7.9 (3.4-12.3) (2) 2.3 (10.5)	Increased risk of RCC in subjects with HCV chronic infection
Gordon SC Cancer Epidemiol Biomarkers Prev 2010	United States	Cohort study Period: 1997-2006	Use of administrative data from Henry Ford Hospital, an integrated healthcare delivery system serving southeastern Michigan. Cancer diagnosis codes in administrative databases [International Classification of Diseases, 9th ed., Clinical Modification (ICD-9-CM) codes in the range of 140 through 208.9]	72487 patients tested for anti-HCV 3057/72487 anti-HCV positive patients 17/3057 (0.6%) with RCC	Control cohort of patients who tested negative for anti-HCV	64006/72487 anti-HCV negative patients 177/64006 (0.3%) with RCC	NR	0.6 (0.3-0.8)	Chronic infection with HCV confers an increased and independent risk for developing RCC
Hofmann JN Eur J Cancer Prev 2011	Sweden	Nationwide register-based cohort- study Period: 1990-2008	HCV diagnosis extracted from the national surveillance database at the Swedish Institute for Infectious Disease Control (SMI). Cancer diagnoses were coded using the seventh revision of the International Classification of Diseases (ICD-7) (ICD-7 codes 180.0 and 180.9)	43000 Lag period after HCV notification (1) None: 38, Expected: 27.1 (2) Three months 33 Expected: 26.5 (3) One year: 29 Expected: 24.9	A non-HCV-infected cohort selected from the general population	215000	Year of birth, sex, and county of residence in Sweden, five subjects never diagnosed with HCV infection were matched to each HCV-infected subject	(1) 0.06 (0.09-0.21) (2) 0.05 (0.08-0.21) (3) 0.05 (0.07-0.21)	In the cohort of HCV-infected subjects, no increased risk of developing kidney cancer but an enhanced risk of non-cancer chronic kidney disease, particularly among women
Malaguarnera M Eur J Int Medicine (2006)	Italy	Case-control study Period: NR	All cancer patients: 236 HCV diagnosis performed with II G ELISA test. Cancers diagnosed at Garibaldi Hospital	15 patients with RCC 8/15 (53%) HCV positive patients	Elderly volunteers evaluated at Garibaldi Hospital, Catania	30/300 (10%)	Age, sex and previous blood transfusions	53.3 (26.5-78.7)	High prevalence of anti-HCV antibodies in patients with renal cancer
Omland LH Clinical Epidemiology 2010	Denmark	Cohort-study Period: 1994-2003	Patients and subjects with HCV infection identified by means of: -The Danish National Hospital Registry (DNHR) -The Danish Cancer Registry People listed in DNHR with at least one diagnosis of acute or chronic HCV infection (ICD-10 B17.1 and 18.2) were included Cancer diagnoses based on the Danish version of the international classification of diseases, 8th revision (ICD-8) until Dec 31, 1993, and 10th version (ICD-10) thereafter	4349 patients with HCV infection in the DNHR 4 renal cancer detected 4/4349	The expected number of cases of cancer after a diagnosis of HCV infection using Danish incidence rates of first cancer diagnoses according to sex, age, and year of diagnosis in 1-year intervals was calculated	Expected number of kidney cancers: 1.11	NR	0.1 (0-0.2)	Association between HCV infection and higher risk of renal cancer development
Swart A BMJ Open 2012	Australia	Cohort-study 1 January 1993 - 31 December 2007	Individuals registered on the Pharmaceutical Drugs of Addiction System, a record of all NSW Health Department authorities that administer methadone or buprenorphine to opioid-dependent people as opioid substitution therapy. Solid cancers classified according to the International Classification of Diseases (ICD), 10th revision, haematopoietic neoplasms and Kaposi sarcomas classified according to the ICD for Oncology, 3rd edition	Patients considered in the study: 29613 Subjects with HCV infection alone: 14892 Observed number of RCCs in HCV-positive cohort: 20 20/14892	Calculation of expected number of incident RCCs	Expected number of RCCs: 18.1	NR	0.1 (0.08-0.20)	No evidence supporting a strong association between HCV infection and RCC development

NR: Not reported; SIR: Standardised incidence ratio; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma.