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

Table 7 Characteristics of available studies, reported in English, assessing the association between hepatitis C virus infection and thyroid cancer

Author/Journal/Publication year	Study design/study period	Diagnosis	Sample size	Control source	Controls	Percentage of HCV-positive cases with95%CI	Main conclusions
Amin J J Hepatol 2006	Community-based cohort-study Period: 1990-2002	Identification of thyroid cancer cases by means of ICD-10- diagnosis codes	Individuals with HCV infection: 75834 Thyroid cancers detected: 9	Incidence observed in the study cohort was compared to expected incidence derived from NSW population cancer rates by calculating standardised incidence ratios	SIR: 0.3 (0.2-0.7)	0.01 (0-0.02)	No evidence supporting an association between HCV infection and thyroid cancer development
Antonelli A Clin Exp Rheumat 2002	Case-control study Period: 1999-2001	FNA PTC	94 patients with HCV-associated MC Patients with PTC and HCV-associated MC/patients with HCV-associated MC: 2/94 (2.1%)	Control group obtained from a sample (2401 individuals) of the general population, 5 controls were randomly associated with each MC patient	0/470	2.1 (0-5)	Possible association between HCV-related MC and thyroid cancer, careful monitoring of the thyroid opportune, during the clinical follow-up of HCV- associated MC patients
Antonelli A Thyroid 2007	Case-control study Period: January 1995 - December 2001	FNA PTC	308 HCV positive patients PTC and HCV positive cases/all HCV positive cases: 6/308 (1.9%)	(1) subjects from an iodine deficient area; (2) subjects from an iodine-sufficient area	PTC cases/all HCV negative controls: (1) 0/616; (2) 1/616	1.9 (0.4-3.4)	High prevalence of thyroid papillary cancer in HCV+ patients, overall in presence of thyroid autoimmunity; careful thyroid monitoring is indicated during the follow-up of these patients
Giordano TP JAMA 2007	Cohort study Period: 1997-2004	Identification of HCV infected subjects by means of ICD-9-CM , diagnosis codes of HCV infection (070.41, 70.44, 070.51, 070.54, V02.62) Identification of thyroid cancer by menas of ICD-9-CM diagnosis codes: 193	HCV-positive cohort: 146394 patients During follow-up, 813 patients in HCV-infected cohort (0.5%) had a HIV diagnosis. 46 patients developed thyroid cancer	Inpatients records from more than 150 United States Veterans Affairs (VA) hospitals in the Patients’ treatment file and outpatients records from any VA facility in the Output Clinic File	HCV- negative cohort: 572293 patients. During follow-up, 35696 uninfected HCV patients (6.2%) had a recorded HCV diagnosis and 1539 patients (0.3%) a HIV diagnosis 274 patients developed thyroid cancer	0.03 (0.02-0.04)	No increased, risk for thyroid cancer in HCV-positive cohort
Montella M Oncol Rep 2003	Case-control study Period 1997-1999	Histological confirmation PTC	HCV positive PTC cases/all PTC cases: 16/130 (12.3%)	Control group including subjects, operated for benign diseases. Cases and controls selected from the hospital tumor registry	242 controls and 311 surgical procedures. HCV positive controls/total controls 18/311	12.3 (6.6-17.9)	Association between HCV and thyroid cancer. This malignancy more readily detectable in countries with a high prevalence of HCV
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 1 thyroid cancer detected	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 thyroid cancers: 0.46	0.02 (0-0.06)	No association between HCV infection and higher risk of thyroid cancer development
Swart A BMJ Open 2012	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 thyroid cancer in HCV-positive cohort: 48	Calculation of expected number of incident thyroid cancer	Expected number of thyroid cancers: 34.4	0.3 (0.2-0.4)	No evidence supporting an association between HCV infection and thyroid cancer development

FNA: Fine needle-aspiration; MC: Mixed cryoglobulinemia; PTC: Papillary thyroid cancer; SIR: Standardised incidence ratio; HCV: Hepatitis C virus.