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Identifying, characterizing, and interrupting the primary cause of a disease is far more effective than diagnosing and treating the disease itself. As the saying goes, “An ounce of prevention is worth a pound of cure.” Together, laboratory and epidemiologic research efforts have identified several viruses and one bacterium as human carcinogens. Research on hepatitis B virus (HBV) and its association with hepatocellular carcinoma (HCC) exemplifies the historical accomplishments, current progress, and challenges remaining for cancer prevention once the cause is known.

In 1965, Blumberg et al. ( 1 ) reported the initial detection of the “Australia antigen,” which was found in serum from an Australian aborigine and is now known as hepatitis B virus surface antigen (HBsAg). During the 1970s, chronic carriage of HBsAg was closely tied to HBV infection during infancy ( 2 ) , and HBsAg was detected in a large fraction of patients with HCC ( 3 ) . In seminal studies, Beasley and colleagues ( 4 ) found that HCC mortality was 223-fold higher for Taiwanese men who were HBsAg-seropositive than for those who were HBsAg-seronegative and that perinatal transmission of HBV could be prevented by administering hepatitis B immune globulin to neonates and an HBV vaccine to infants ( 5 ) . These findings motivated the initiation of Taiwan's population-wide HBV screening and vaccination program ( 6 ) . During the first 20 years of this ongoing program, there have been marked reductions in chronic carriage of HBsAg, HCC incidence, and liver cancer mortality among children in Taiwan ( 7 , 8 ) .

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