In England and Wales, the incidence of cancers of the liver, gallbladder and biliary tract increased over the last three decades of the 20th century, particularly in males. The rates of intrahepatic bile duct cancer increased dramatically in both sexes, whereas the rate of liver cell cancer increased significantly in males, but not in females. In 1999–2001, liver cell cancer was the most common subsite in males and was twice as common as intrahepatic bile duct cancer. In contrast, intrahepatic bile duct cancer was the most common subsite in females. These incidence trends show some divergence from the previously reported mortality statistics. In addition, there were dramatic reductions in the incidence of extrahepatic bile duct and gallbladder cancers in both men and women.
In terms of histological type, the trends were quite similar between the sexes. The incidence of cholangiocarcinoma increased by around 16-fold, and that of hepatocellular carcinoma by threefold over the last three decades of the 20th century. These increases were too large to be accounted for by a shift in coding from other histological types over the period. Our examination of the agreement between subsite and histological type showed that over 80% of cholangiocarcinomas were intrahepatic (coded as intrahepatic bile duct cancer) and around 95% of hepatocellular carcinomas were coded as liver cell cancer.
Our use of cancer incidence data has provided the opportunity to examine long-term incidence trends for these cancers in England and Wales, where only mortality data have recently been reported. The information on histological type of each cancer, the proportion diagnosed on the basis of histology and our age-specific analyses have allowed greater examination of the possibility of ascertainment bias than is possible with mortality statistics. As might be expected, the trends in incidence are similar to those reported for mortality in England and Wales. Indeed, the mortality trends in both liver cell cancer and intrahepatic bile duct cancer for both men and women up until 1996 showed, as we do, that in women intrahepatic bile duct cancer was the most common type, in contrast to men, in whom liver cell cancer was most common. It might be argued that the increase we show in intrahepatic bile duct cancer reflects greater ascertainment consequent upon improved endoscopic and radiological techniques. Indeed, this interpretation has some support, since we found that the proportion of all liver, gallbladder and biliary tract cancers that were diagnosed on the basis of histological verification from a biopsy increased between 1993 and 2001. It is also possible that some of the increase in intrahepatic bile duct cancer may be due to diagnostic transfer from cases that were previously coded as extrahepatic bile duct cancer, although the reductions in extrahepatic bile duct cancer over the period were small.
Imaging modalities such as computerised tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) have been available in most UK hospitals since the mid-1980s (McCune, 1988
; Scott and Atkinson, 1989
), but the increase in the incidence of intrahepatic bile duct cancer has continued at the same rate even in the last decade. Therefore, while some of the rise might be explained by increased ascertainment (i.e. increased use of imaging modalities over time in line with the increasing incidence), and certainly the increase in the proportion of cases diagnosed on the basis of histology suggests that this is partly responsible, we believe that this is not sufficient explanation. In particular, our analysis by histological type showed that the increase in the incidence of cholangiocarcinoma was far greater than the decreases in carcinoma NOS and neoplasm NOS+other. The marked decrease in gallbladder cancer is also unlikely to be anything other than a true trend, as ascertainment is unlikely to be an issue for this particular malignancy. Furthermore, diagnostic transfer does not readily explain why the increase is overwhelmingly in intrahepatic cholangiocarcinoma or why there are the differences in the age-specific patterns seen in .
The reasons behind the increasing incidence of intrahepatic cholangiocarcinoma are unclear. Two recent studies from the USA suggested that the same risk factors could predispose to both the main forms of primary liver cancer (Davila et al, 2005
; Shaib et al, 2005
). Shaib et al (2005)
found hepatitis C infection, alcoholic liver disease and liver cirrhosis, well-established risk factors for hepatocellular cancer, to be strongly associated with intrahepatic cholangiocarcinoma. Intriguingly, using a similar study design, they found comparable associations for the same risk factors and hepatocellular carcinoma (Davila et al, 2005
). Our findings would, however, suggest that these cancers do not necessarily have similar risk factors.
In conclusion, we have found increases in the incidence of primary liver cancer, which have been particularly dramatic for intrahepatic bile duct cancer, over the last three decades of the 20th century in England and Wales. There has been a halving in the incidence of gallbladder cancer and a reduction of a third in extrahepatic bile duct cancer. Cholangiocarcinoma became the commonest type of primary liver cancer in females in contrast to males, in whom hepatocellular carcinoma remains the most common. The trends in the incidence of intrahepatic bile duct cancer and liver cell cancer follow strikingly different patterns, overall and in the older age groups, suggesting that the two main types of primary liver cancer are unlikely to completely share common aetiologies.