Viral Infection and Liver Cancer: A Global Health Crisis

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It is estimated that at least 15% of all cancers worldwide can be attributed to infectious etiologies, mostly viral infections. At this year’s ASCO Annual Meeting, an intriguing session on virally induced cancers provided critical clues that could be of real practical value in advancing our battle against cancer, both in the clinic and on the prevention front.1

Moreover, virally induced cancers will have a predominant impact on the world’s rising cancers rates, especially in the economically developing nations. John D. Groopman, PhD, Johns Hopkins University, Baltimore, opened with a sobering worldview of cancer epidemiology. “Currently, almost 50% of the world’s cancer deaths occur in Asia, and by 2050, that percentage will rise to about 70%.”

Clear Demographic Connection

To illustrate the viral connection to cancer prevalence, Dr. Groopman focused on liver cancer, which is a major killer of men in Southeast Asia and sub-Saharan Africa. “In terms of its global impact, liver cancer is the third leading cause of cancer death, with more than 80% of these deaths occurring in the world’s economically developing regions,” said Dr. Groopman. He added that there are approximately 500 million hepatitis B virus (HBV) carriers worldwide that will convert into about 100 million cancer deaths during the rest of the 21st century.

“This looming crisis is something that we probably won’t be able to attenuate in the near future, given the disease’s etiology and our lack of broad-based intervention strategies. Right now, about 95% of liver cancer’s etiology is known; however, translating that knowledge into actionable therapies and prevention is our huge challenge,” noted Dr. Groopman.

He then gave an overview of our current knowledge of hepatocellular carcinoma. “The classic prospective study by Beasley and colleagues of 22,707 Chinese men in Taiwan, was one of the first analyses to demonstrate the power of an immunologic biomarker by showing that the presence of the HBV antigen was major driving force in the relative risk of developing liver cancer,” said Dr. Groopman.

“However, when we looked at these different populations, a geographic variation of hepatocellular carcinoma in male HBV carriers suggested that the incidence of [the disease] is not driven solely by the HBV infection, in fact, environmental risk factors play a large role. This finding led to a number of prospective studies in the early 1980s in areas of China where liver cancer incidence is exceedingly high,” said Dr. Groopman.

HBV and Aflatoxin: A Deadly Synergy

Over the past 20 years, Dr. Groopman and colleagues have prospectively followed more than 18,240 men. “Using the HBV surface antigen as a biomarker along with a number of aflatoxin biomarkers, particularly the DNA damage products of aflatoxin, we found a statistically significant increase in liver cancer in those that were HBV-positive (relative risk = 7.3) or aflatoxin-positive (relative risk = 3.4). However, in those individuals who were HBV-positive and aflatoxin-positive, there was a greater than multiplicative relative interaction between the virus antigen and the environmental mycotoxin, leading to a relative risk value of 60 for developing [hepatocellular carcinoma],” said Dr. Groopman.

“Over the past decades, we have gained a lot of knowledge about HBV, in particular, the mutations on the X-gene, which produces a protein, called the X-protein that embellishes the development and proliferation of HBV, which in turn leads to the sequential infection of the hepatocytes in people,” explained Dr. Groopman.

Dr. Groopman commented that we are able to detect this biomarker up to 20 years prior to the development of hepatocellular carcinoma. “This is critically important because, in Africa and Asia, children are infected with HBV before the age of 2 years. So, if you don’t have a health-care mechanism for vaccinating children at birth, these children are going to be infected, and consequently will have a high lifetime risk of liver cancer,” said Dr. Groopman.

Prevention Strategies

One of major public health challenges in dealing with virally induced liver cancer is that much of the incidence of HBV infection is in regions of the world where economic and political hurdles impede effective strategies. Moreover, the global recession has reduced the funding of major health-care bodies, limiting their ability to launch vaccination programs.

“About 79% of [World Health Organization] member states have adopted universal childhood HBV vaccination policies as of 2005. However, according to the latest birth cohort data, less than one-third of the world’s children younger than 1 year of age have been vaccinated for HBV,” said Dr. Groopman, adding that in the two regions with the highest incidence of liver cancer—south eastern Asia and Africa—the percentages of children vaccinated for HBV are 9% and 6%, respectively.

The frustration for public health-care professionals is that much of the world’s liver cancer is preventable. Dr. Groopman pointed to a 20-year follow-up study published in the Journal of the National Cancer Institute in 2009.2 “The study revealed about a 70% drop in liver cancer cases among 6- to 19-year-olds who were vaccinated for the hepatitis B virus at birth. But it is going to take the rest of the century for vaccination strategies to eradicate this virus,” said Dr. Groopman. ■

Disclosure: Dr. Groopman reported no potential conflicts of interest.


1. Groopman J: Virally mediated oncogenesis: Liver cancer and hepatitis. 2012 ASCO Annual Meeting. Extended Education Session. Presented June 1, 2012.

2. Chang MH, You SL, Chen CJ, et al: Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: A 20-year follow-up study. J Natl Cancer Inst 101:1348-1355, 2009.