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

Table 3 Characteristics of available studies, reported in English, designed to assess the association between hepatitis C virus infection and pancreatic cancer risk

First author/Journal/Publication year	Study design/study period	PAC diagnosis	HCV positive PAC (n)/total PAC cases (n)	Control source	HCV positive controls (n)/controls (n)	Percentage of HCV-positive cases with 95%CI	Main conclusions
Amin J J Hepatol 2006	Community-based cohort-study Period: 1990-2002	Identification of pancreatic cancer cases by means of ICD-10- diagnosis codes	-Individuals with HCV infection: 75834 PAC detected: 17/75834 (0.02%)	Incidence observed in the study cohort was compared to expected incidence derived from NSW population cancer rates by calculating standardised incidence ratios	SIRs: 1.4 (0.8-2.2)	0.02 (0.01-0.03)	No evidence supporting an association between HCV infection and PAC development
Chang MC World J Gastroenterol 2014	Case-control study Period: 2000-2013	Histological or citological	22/585 (3.8%)	Controls were individuals recruited from a free screening program in a community located in Northern Taiwan	45/1716 (2.6%)	3.8 (2.2-5.3)	HCV infection not associated with higher risk of PAC development, after adjustement for age, sex, diabetes and smoking (independent risk factors for PAC)
El Serag Hepatology 2009	Cohort study Cohort: 718687 patients PAC detected: 617 Period: 1988-2004	Identification of PAC cases by means of ICD-9-CM diagnosis codes (157.0, 157.1, 157.2, 157.3, 157.8, 157.9) Identification of HCV infected subjects by means of ICD-9-CM diagnosis codes (070.41, 070.44, 070.51, 070.54 and V02.62)	146394 patients in HCV-infected cohort PAC detected:140/146,394 (0.09%)	Sources included inpatients records from more than 150 of USA Veterans Affairs (VA) hospitals in the Patients treatment file and outpatients records from any VA facility in the Output Clinic File	572293 patients in HCV-uninfected cohort PAC detected: 477	0.09 (0.08-0.11)	Higher risk of PAC in patiens of HCV-infected cohort , but this association was attenuated after adjustement for alcohol use, pancreatitis, choledocholitiasis, cholelithiasis or primary sclerosing cholangitis
Hassan MM J Clin Oncol 2008	Hospital-based case-control study Period: 2000-2007	Histological confirmation	6/474 (1.5%)	Community-based (healthy genetically unrelated family members of patients with cancer other than pancreatic, GI, lung or head cancers)	9/872 (1%)	0.8 (0.02-1.6)	HCV infection not associated with higher risk of PAC development
Huang J Br J Cancer 2013	Retrospective Nationwide cohort study 197208 participants: Period: 1990-2006	Identification of PAC cases from the Swedish Cancer Register (International Classification of Disease ICD-7: 157) and from the Cause of Death Register (ICD-9: 157; ICD-10: C25)	Individuals in HCV reference cohort: 39442 PAC detected: 34/39442 (0.09%)	Control population obtained from the national surveillance database at the Swedish Institute for Infectious Disease Control. The expected numbers of calculated PAC from the observed person-time in each 5-yr age group by sex and the corresponding Swedish population incidence rates.	Expected number of PAC: 16.5	0.09 (0.05-0.11)	Statistically significant increased risk of PAC development
Omland LH Clinical Epidemiology 2010	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 4/4349 PAC detected (0.1%)	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-yr intervals was calculated	Expected number of PAC: 1.01	0.1 (0-0.18)	Association between HCV infection and higher risk of PAC development
Qiwen Ben Pancreas 2012	Double-centre ongoing hospital-based case-control study. Period: January 1, 2004- August 31, 2008 January 1, 2003- Octobet 31, 2009	Histological or citological confirmation	14/943 (1.5%)	Patients admitted to the same Hospitals (Ruijin Hospital and Changai Hospital, Shangai for any acute conditions)	12/1128 (1.1%)	1.5 (0.7-2.2)	No higher HCV prevalence in patients with PAC in comparison with controls
Swart A BMJ Open 2012	Cohort-study Patients considered in the study: 29613 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	Subjects with HCV infection alone: 14892 Observed number of PAC in HCV-positive cohort: 20/14892 (0.1%)	Calculation of expected number of incident PAC	Expected number of PAC: 7.12	0.13 (0.08-0.21)	Increased risk of PAC in patients with HCV infection
Woo SM J Korean Med Sci 2013	Case-control study Period: 2001-2011	Histological or radiological/clinical confirmation	753 patients with PAC 724/753 with available anti-HCV test 21/724 (2.8%)	Individuals subjected to routine health examination in the Cancer Screening Cohort	36/3012 (1.2%)	2.9 (1.7-4.1)	Seropositivity for anti-HCV, infection, may increase the risk of developing PC in Korea

NR: Not reported; SIR: Standardised incidence ratio; HCV: Hepatitis C virus; PAC: Pancreatic cancer.