Primary liver cancer is the fifth most common cancer world wide and the third most common cause of cancer mortality (Parkin 2001). Globally, over 560,000 people develop liver cancer each year and an almost equal number, 550,000, die of it. Liver cancer burden, however, is not evenly distributed throughout the world (Fig. 16.1). Most hepatocellular carcinoma (HCC) cases (>80%) occur in either sub-Saharan Africa or in Eastern Asia. China alone accounts for more than 50% of the world's cases (age-standardized incidence rate (ASR) male: 35.2/100,000; female: 13.3/100,000). Other high-rate (>20/100,000) areas include Senegal (male: 28.47/100,000; female: 12.2/100,000), The Gambia (male: 39.67/100,000; female: 14.6/100,000), and South Korea (male: 48.8/100,000; female: 11.6/100,000). North and South America, Northern Europe and Oceania are low-rate (<5.0/100,000) areas for liver cancer among most populations. Typical incidence rates in these areas are those of the US (male: 4.21/100,000; female: 1.74/100,000), Canada (male: 3.2/ 100,000; female: 1.1/100,000), Colombia (male: 2.2/100,000; female: 2.0/100,000) UK (male: 2.2/100,000; female: 1.1/100,000), and Australia (male: 3.6/100,000; female: 1.0/100,000). Southern European countries, typified by rates in Spain (male: 7.5/100,000; female: 2.4/100,000), Italy (male: 13.5/100,000; female: 4.6/100,000), and Greece (male: 12.1/100,000; female: 4.6/100,000) are medium rate (5.0-20.0/100,000) (Ferlay 2001). HCC accounts for between 85% and 90% of primary liver cancer. One noteworthy exception is the Khon Kaen region of Thailand, which has one of the world's highest rates of liver cancer (ASR 1993-1997 male: 88.0/100,000; female: 35.4/100,000) (Parkin 2002). However, due to endemic infestation with liver fl ukes, the major type of liver cancer in this region is intrahepatic cholangiocarcinoma rather than HCC (Okuda et al. 2002). Encouraging trends in liver cancer incidence have been seen in some of the high-rate areas (McGlynn et al. 2001). Between 1978-82 and 1993-97, decreases in incidence were reported among Chinese populations in Hong Kong, Shanghai and Singapore (Parkin 2002). In addition to these areas, Japan also began to experience declines in incidence rates among males for the first time between 1993 and 1997 (Fig. 16.2). Many high-rate Asian countries now vaccinate all newborns against the hepatitis B virus (HBV) and the effect on HCC rates has already become apparent. In Taiwan, where national newborn vaccination began in 1984, HCC rates among children aged 6-14 years declined significantly from 0.70/100,000 in 1981-1986 to 0.36/100,000 in 1990-1994 (Chang et al. 1997). It is too soon yet for HBV vaccination to have had an effect on adult rates, but other public health measures may have contributed to declines in HCC incidence in high-risk areas of China. A Chinese government program started in the late 1980s to shift the staple diet of the Jiangsu Province from corn to rice may have limited exposure to known hepatocarcinogen afl atoxin B1 (AFB1) in this area (Yu 1995). Similarly, another Chinese public health campaign initiated in the early 1970s to encourage drinking of well rather than pond or ditch-water, may have decreased consumption of microcystins, cyanobacteria- produced compounds demonstrated to be hepatocarcinogenic in experimental animals. In contrast, registries in a number of low-rate areas reported increases in HCC incidence between 1978-82 and 1993-97. Included among these registries are those in the US, UK, and Australia. Reasons for both the decreased incidence in high-rate areas and the increased incidence in low-rate areas are not yet clear, suggesting that each area will be an important case study. It has been widely hypothesized, however, that increased incidence in low-rate areas may be related to greater prevalence of hepatitis C virus (HCV) infection in these areas. © 2008 by Blackwell Publishing.