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

Table 6 Characteristics of available studies, reported in English, assessing the association between hepatitis C virus infection and oral or skin cancer

Author/Journal/Publication year	Study design/study period	Diagnosis	Sample size (cases/controls)	Control source	HCV positive controls/controls	Percentage of HCV-positive cases with 95%CI	Main conclusions
Amin J J Hepatol 2006	Community-based cohort-study Period: 1990-2002	Identification of skin/oral cancer cases by means of ICD-10- diagnosis codes	Individuals with HCV infection: 75834 Skin/oral cancer: 19 including , mouth (7 cases), tongue (6 cases), tonsil (6 cases) no skin cancers described	Incidence observed in the study cohort was compared to expected incidence derived from NSW population cancer rates by calculating standardised incidence ratios	SIR: Mouth: 1.5 (0.7-3.2) Tongue: 1.1 (0.5-2.4) Tonsil: 2.1 (1-4.8)	0.02 (0.01-0.03)	No evidence supporting an association between HCV infection and skin/oral cancer development, low increased risk for tonsil cancer
Eftekharian A Eur Arch Otorhinolaryngol 2012	Case-series 107 patients with SCCHN Period: October 2008-June2010	Histological confirmation: SCCHN	1/107 (0.9%)	NR	NR	0.9 (0-2.7)	HCV at least in Iran not a risk factor for SCCHN
Gandolfo S Oral Oncol 2004	Case-series 402 patients with OLP Patients with available HCV test: 357 HCV positive patients: 69/357 (19.3%) Period: January 1988 - July 1999	During the follow-up period: 9 patients developed an oral squamous cell carcinoma Histological confirmation: OSCC	HCV positive patients with OSCC: 4/9 (44.5%)	NR	NR	44.5 (11.9-76.9)	Possible increased risk for OSCC in HCV-related infection in patients oral lichen planus (OLP)
Nagao Y J Oral Pathol Med 1995	Case-series 100 patients with oral cancer enrolled Period: January 1989-October 1993	Histological confirmation: Different histotypes	24/100 (24%)	Patients with non-malignant disease receiving dental treatment at the Department of Oral Surgery of the Kurume University Patients with gastric cancer	(1) 11/104 (10.6%); (2) 12/113 (10.6%)	24 (15.6-32.3)	HCV causing pathologic changes in the oral cavity, with HCV involved in cancerization
Nagao Y J Oral Pathol Med 2000	Biopsies of 36 patients, including: (1) OLP: 19; (2) Oral cancer: 17 Period: NR	Histological confirmation: Well-differentiated SCCHN	(1) 14/19 (73.7%); (2) 7/17 (41. 2%)	Biopsies of 10 patients, including: (3) Non-malignant disease with HCV (4) Non-malignant disease without HCV	(3): 6 (4): 4	(1) 73.7 (53.8-93.4); (2) 41.2 (17.8-64.5)	HCV causing pathologic changes in the oral cavity, with HCV involved in cancerization
Nobles J Laringoscope 2004	Case-series 100 patients with SCCHN enrolled. Period: June 1991-December 2002	Histological confirmation: SCCHN	21/100 (21%)	NR	NR	21 (13-28.9)	A large number of patients (21%) with SCCHN, included in this study, coinfected with HCV. This prevalence is significantly increased when compared with the general population (1.4%) or the population at VA hospitals (9.9%)
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 oropharyngeal cancers 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 oropharyngeal cancers: 1.73	0.1 (0-0.2)	No sssociation between HCV infection and higher risk of oropharyngeal cancer development
Su FH PlosOne 2012	Nationwide Population-Based Cohort Study HCV positive patients: 5311 HCV and HBV positive patients: 3519 Period: 1996-2008	Data obtained from the Taiwan National Health Insurance Research Database (NHIRD). HCV cases identified by means of ICD-9-CM diagnosis codes (ICD-9-CM: 070.41, 070.44, 070.51, 070.54, V02.62)	(1) 21/5311; (2) 9/3519	Controls identified by means of a systematic random sampling method to select 4 insured people without viral hepatitis for every insured person with viral hepatitis during the same period	147/84796	(1) 0.4 (0.2-0.5); (2) 0.3 (0.09-0.4)	HCV infection is a risk factor for oral cavity cancer. In addition, subjects with HCV infection tend to be at early onset risk for oral cavity malignancy
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 following cancer in HCV-positive cohort: (1) Tonsil: 10; (2) Mouth:8; (3) Salivary gland: 4; (4) Tongue: 9 Total: 31	Calculation of expected number of incident tonsil/mouth/salivary gland/tongue cancers	Expected number of oral cancers: Tonsil: 2.96 Mouth; 3.54 Salivary gland: 2.75 Tongue:5.35	0.2 (0.1-0.3)	Possible association between HCV and tonsil/mouth cancers. No association between HCV infection and tongue/salivary cancers
Takata Y Oral Diseases 2002	Case series Patients with anti-HCV antibodies: 2613 HCV positive patients: 151/2613 (5.8%) Period: January 1989 -December 1998	Histological confirmation Histotype not reported	25/245 (10.2%)	NR	NR	10.2 (6.4-13.9)	High HCV antibody prevalence in patients with oral cancer. Possible no important association between oral cancer and HCV infection, with increased prevalence, depending on higher age of anti-HCV positive patients

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