Temporal changes in liver cancer incidence rates in Japan: Accounting for death certificate inaccuracies and improving diagnostic techniques


  • This publication is based on research performed at the Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan. RERF is a private nonprofit foundation funded equally by the Japanese Ministry of Health and Welfare and the U.S. Department of Energy through the National Academy of Sciences.


Primary liver cancer (PLC) rates have risen dramatically during the past few decades in some regions, particularly in Japan, where PLC is now the third major cause of cancer death. PLC is one of the most difficult tumors to diagnose correctly, because (i) the liver is a frequent site of cancer metastasis and (ii) death from PLC is often attributed to cirrhosis or chronic hepatitis. Also, because the disease is often rapidly fatal, a large proportion of liver cancer cases are identified based on death certificates alone without confirmation by clinical records. Thus, worldwide differences in published incidence rates for this disease reflect regional or national differences in both the accuracy of death certificates and the sensitivity of diagnostic methods. By comparing death certificate causes of death with those based on pathology review, we were able to adjust 1958–1994 incidence rates for a large Japanese cohort for these errors. Although the death certificate false-positive error rate declined, the false-negative error rate remained high throughout the study. The introduction of improved liver cancer diagnostic methods in Japan in the early 1980s was associated with a sharp increase in PLC incidence. We conclude that errors in death certificate causes of death and changes in liver cancer diagnostic techniques have had an important impact on the reported incidence of this disease. Taking these factors into account, rates of hepatocellular carcinoma rose between 2.4- and 4.3-fold in our Japanese cohort from 1960 to 1985, peaked about 1993 and declined thereafter. Incidence rates of cholangiocarcinoma remained stable through 1987. © 2001 Wiley-Liss, Inc.