Transcript Epidemiology of Hepatocellular Carcinoma (Liver Cancer)

Primary liver cancer is the fifth most
common cancer in the world and the
third most common cause of cancer
mortality
 Hepatocellular carcinomas (HCCs) are
malignant tumors of liver parenchymal
cells
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1.3% of estimated incident cancer cases
are in the liver and intrahepatic bile duct
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Incidence rates are higher for males
than females (2-4:1)
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Higher incidence for African Americans
and Asians than whites
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5 year survival rate is approximately 6.9%
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One of the most common malignancies
in eastern Asia and sub-Saharan Africa
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Incidence up to 90.0/100,000 in some
parts of the world
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More than 600,000 deaths in 2002
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44% of the world’s cases occur in China
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Incidence increases with age then
plateaus when the peak is reached,
around 55 to 65 in the United States
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Ethnic and familial clustering have been
reported
› Possible interaction between Hepatitis
infection and a major gene
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Implicated as the probable cause of HCC
in at least 80% of cases worldwide
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About 5% of the world’s population(350
million people) is chronically infected with
HBV
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Lifetime risk of HCC for these individuals is
estimated at 10-25%
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In low prevalence areas (such as the U.S.), is
spread mainly by exposure to contaminated
blood through IV drug use or sexual contact
with an HBV carrier
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In highly endemic areas of Asia, about half of
chronic infections result from perinatal
transmission
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Can also be transmitted through household
contacts, contaminated blood or blood
products, organ transplantation, or needle-stick
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Areas of the world with high mortality rates for
HCC also have high HBV infection rates
Cirrhosis is closely related with chronic HBV
infection, at least 80% of liver cancers occur in
cirrhotic livers
Case control studies in all regions of the world
have shown that chronic HBV infection is much
more common in HCC cases than controls
› OR ranged from 5:1 to 65:1
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Prospective studies of chronic HBV carriers have
shown very high relative risks for HCC
› 400 and 500 /100,000 compared with 5/100,000
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Prevention of HBV reduces risk of subsequent HCC
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Viral DNA is integrated into host cell
genome
› HBV sequences are present in HCCs
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One gene may have important
promotional role in
hepatocarcinogenesis, but the
mechanism is not yet known
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Vaccination
› 90% preventable with proper use of hepatitis
B vaccine
› Universal immunization of newborns in
Taiwan is associated with at least a 50%
reduction in incidence of HCC among
adolescents
› Part of WHO universal childhood vaccination
› Cost reduced from $100 to $1 per pediatric
dose
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Major viral cause of liver cancer in areas
with low HBV prevalence
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About 3% of the world’s population (170
million people) is chronically infected
with HCV
› 3-4 million new infections each year
› 2-4% with chronic HCV develop HCC
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Transmitted by parenteral route
› Intravenous drug use
› Hemodialysis
› Blood transfusion
› Exposure to blood of infected patient
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Other routes probably exist but have not
been identified
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Many epidemiological studies have
indicated association
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Detection of HCV RNA in tumor and
nontumor cirrhotic liver tissue of patients
with HCC
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Alcohol is a significant risk factor for liver
cancer in areas with low HBV and HCV
incidence
› Evidence indicates that alcohol causes
cirrhosis which in turn increases risk of HCC
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In high incidence areas, alcohol may
exacerbate viral liver damage and
promote tumor development
Aflatoxins
 Thorotrast (X-ray
contrast material)
 Vinyl Chloride
 Steroid Hormones
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Schistosomiasis
Liver flukes
Iron
Tobacco
Diet
Cirrhosis
 Immune Function
 Genetic Susceptibility
 Hemochromatosis
 Other Inherited Metabolic Disease
 Diabetes Mellitus
 Non-alcoholic Steatohepatitis
 Primary Sclerosing Cholangitis
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Limit exposure of the general populations
and workers in certain industries to
hepatocarcinogens
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Reduce transmission of hepatitis by IV drug
use through counseling about risks
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Prevent HBV infection (vaccination)
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Serum alpha-fetoprotein (AFP)
› Limitations:
 Senstitivity and specificity
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Ultrasonography of the liver
› Limitations
 Quality of equipment
 Skill of operator in identifying small tumors
 Cost
Vaccine for HCV
 Understand molecular pathogenesis of
HCC
 New targets for chemoprevention of
HCC and therapies for established HCC
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80-95% of HCCs are associated with
chronic infection with Hepatitis B or C
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HBV infection is preventable by
immunization and HCV is preventable
through public health measures
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If opportunities for intervention are acted
upon, HCC could become a minor
cause for cancer mortality in the future
Cancer Epidemiology, 3rd ed. 2006.
Oxford University Press
 Centers for Disease Control
 American Cancer Society
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