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

Abstract

Aim: To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers.

Methods: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer.

Results: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence.

Conclusion: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association.

Keywords: Cancer; Cholangiocarcinoma; Extra-hepatic malignancies; Hepatitis C virus; Hepatocellular carcinoma; Neoplasm; Pancreatic cancer; Risk factors.

Figure 1

Prevalence of chronic hepatitis C virus status in different coutries worldwide. HCV: Hepatitis C virus.

Figure 2

Number of studies and meta-analyses, assessing the association between hepatitis C virus infection and different types of malignancies, included in the present systematic review. References are reported in the supplementary section.

Figure 3

Age-standardized incidence rates of each malignancy per 100000 person-years are reported for sex and for different countries. A: Incidence rates of non-hodgkin-lymphomas (GLOBOCAN 2012); B: Incidence rates of cholangiocarcinoma (by Shin HR, Asian Pacific Journal of Cancer Prevention 2010; 11); C: Incidence rates of pancreatic cancer (GLOBOCAN 2012); D: Incidence rates of breast cancer (GLOBOCAN 2012); E: incidence rates of kidney cancer (GLOBOCAN 2012); F: Incidence rates of oral/skin cancers (GLOBOCAN 2012); G: Incidence rates of thyroid cancer (GLOBOCAN 2012).