HCV infection increases risk of several non-liver-related cancers in elderly people

Hepatitis C virus (HCV) infection is associated with a range of non-liver-related cancers, investigators from the United States report in Cancer. The study population comprised over 1.6m elderly people with cancer and 200,000 closely matched cancer-free controls. Overall, cancer incidence was higher among people with HCV antibodies, as was incidence of several specific malignancies including cancers of the liver, bile ducts, pancreas, certain skin cancers, myelodysplastic syndrome, and diffuse large B-cell lymphoma. The investigators estimated that elimination of HCV infection would have only a modest effect on the risk of many of these cancers.

“Our analyses of a large, population-based data set of elderly individuals demonstrate that, along with HCC [hepatocellular carcinoma], several additional cancers are associated with HCV infection,” comment the investigators. “Although the introduction of direct-acting antivirals has dramatically improved cure rates, HCC risk still remains relatively high in infected individuals who have cleared the virus – particularly elderly individuals.”

An estimated 3m individuals in the United States have HCV infection. Many of these infections involve individuals born between 1945 and 1965, the “Baby Boomer” generation. This age group has been prioritised for HCV screening.

HCV infection is known to increase the risk of HCC and non-Hodgkin lymphoma. Some data suggest that the infection also increases the risk of other cancers.

However, few studies have examined the association between HCV infection and non-liver-related cancers. A team of US investigators therefore analysed data collection via the Surveillance, Epidemiology and End Results (SEER) surveillance programme to determine the association between HCV and the risk of 43 specific cancers. Because of the ageing of the Baby Boomer generation, the investigators focused on people aged 66 years and older.

Elderly people receiving care between 1993 and 2011 were eligible for inclusion. The authors identified 1,623,538 people with cancer. These individuals were matched with cancer-free individuals of the same age, sex, race and calendar year of follow-up.

Prevalence of HCV and hepatitis B virus (HBV) was higher among people with cancer compared to the controls (0.7% vs 0.5%; 1.2% vs 1.1%). A similar proportion of people in both groups had HIV infection (0.4%). Although the differences were small, compared to the controls, people with cancer had a higher prevalence of cirrhosis, diabetes mellitus, smoking and drug abuse. They were also more likely to be high school graduates and to reside in areas with higher median incomes.

Overall, HCV prevalence was higher among cases than controls (0.7% vs 0.5%; aOR = 1.32; 95% CI, 1.32-1.42, p < 0.001).

Moreover, there was a significant association between HCV and an increased risk of several specific cancers:

• Liver (aOR = 31.5; 95% CI, 29.0-34.3)
• Intrahepatic bile duct (aOR = 3.40; 95% CI, 2.52-4.58)
• Extrahepatic bile duct (aOR = 1.90; 95% CI, 1.41-2.57)
• Pancreas (aOR = 1.23; 95% CI, 1.09-1.40)
• Anus (aOR = 1.97; 95% CI, 1.42-2.73)
• Non-melanoma non-epithelial skin cancer (aOR = 1.53; 95% CI, 1.15-2.04)
• Myelodysplastic syndrome (MDS) (aOR = 1.56; 95% CI, 1.33-1.93)
• Diffuse large B-cell lymphoma (DLBCL) (aOR = 1.57; 95% CI, 1.34-1.84)

The associations between HCV and these cancers remained in sensitivity analyses excluding people with HIV and HBV and restricted to people without documented alcohol abuse or cirrhosis.

The investigators estimated that eliminating HCV would reduce the risk of liver cancer by 16%. However, elimination would only have a modest impact on the risk of cancers of the bile ducts, pancreas, MDS and DLBCL (1.15%-0.28%).

“We observed significant associations between HCV infection and several cancers other than liver cancer, notably intrahepatic and extrahepatic cholangiocarcinomas and DLBCL,” conclude the authors. “Studies are needed to strengthen the evidence linking HCV infection to these cancers and to further elucidate biological mechanisms.”