Previous studies have indicated that the incidence of HCC in the United States is higher among males than females and higher among blacks and Asians/Pacific Islanders than whites (8
). We extend these findings by reporting the magnitude of these differences at the national level, and we show that the disparity between Asians/Pacific Islanders and whites decreased over the 6-year study period because rates increased among whites but not among Asians/Pacific Islanders. We also demonstrate that HCC incidence rates vary substantially among U.S. Asian/Pacific Islander subpopulations, with Vietnamese and Korean subgroups having the highest rates. Previous studies comparing rates between Asian/Pacific Islander groups in the United States were based on older data or did not differentiate HCC from other liver cancers (11
Hepatitis B, a primary cause of HCC, is endemic in Southeast Asia, China, and other Asian countries, where most infections are acquired in early childhood through either mother-to-infant transmission or exposure to chronically infected household members (25
). We found that most Asian/Pacific Islander patients with HCC were foreign-born and, therefore, likely to have acquired hepatitis B at birth or during early childhood and to have been infected for many years. Because measures to prevent perinatal hepatitis B transmission did not become available until the 1980s, most U.S.-born Asians/Pacific Islanders in our study most likely acquired their infections in a similar manner (26
). We were unable to compute HCC incidence rates by birthplace because population denominators were not available by this variable. However, previous research reports that rates of liver cancer are higher for males born in Asia than for Asian males born in the United States, who in turn have rates higher than those for white males in the United States (21
The racial/ethnic differences in age-specific incidence and trends for HCC that we found most likely reflect differences in patterns of chronic hepatitis B and hepatitis C as well as host factors and the modulating effects of cofactors such as concomitant infections, alcohol intake, and diabetes mellitus (5
). The limited etiologic data available suggest that hepatitis B has been the major cause of HCC among Asians/Pacific Islanders and that hepatitis C is the leading cause overall and predominates among white, black, and Hispanic patients with HCC in the United States (28
). These data are for select groups of patients, however, many of whom received a diagnosis of HCC 10 or more years ago. Our ability to ascribe current HCC incidence to different etiologies is very limited. Surveillance for new hepatitis B and C virus infections, which have declined considerably in incidence over the past 2 decades, is of limited relevance because HCC typically develops after a lag time of 2 to 4 decades after hepatitis B or C virus infection (31
In the United States, national seroprevalence surveys have shown that chronic hepatitis C is approximately 3 times more common than chronic hepatitis B, but the surveys provide limited data by race/ethnicity and region (32
). Hepatitis C has a marked cohort effect, with prevalence being highest among people born from 1945 through 1964. Most of these people became infected during the 1960s through the 1980s, when incidence was highest, and are now at increased risk of developing chronic liver disease (32
). Much of the recent increase in HCC incidence, and the higher increase in the age group 45–59 years, most likely reflects the aging of these cohorts. Etiologic studies at the individual level are needed to confirm the associations with HCC and to extend previous findings. For this research, various approaches should be explored, including automated capture of available data from electronic health records and other data sources and linkages between the NPCR and SEER programs and registries for chronic hepatitis B and C in states where these registries are well-established.
Our study has certain limitations. First, we were unable to analyze etiology because this information is not captured by the NPCR and SEER registries. Second, information on birthplace from the SEER and California registries may not be generalizable because people with unknown birthplaces are more likely to be born in the United States and because the SEER population tends to be more urban and foreign-born than does the general U.S. population (8
). Third, because the NPCR program was established recently, we were unable to estimate long-term trends in HCC rates at the national level. Fourth, the population coverage for the South was approximately 63%, and the rates for states that were excluded in this region or elsewhere may differ from those we report here. Fifth, increase in the use of noninvasive methods of diagnosis (e.g., radiography) could result in inclusion of more false-positive cases over time. We obtained similar results, however, when we restricted the analysis to histologically confirmed cases (data not shown). Finally, better reporting of HCC over time might account for the temporal increase. The proportion of all primary liver cancers with poorly specified morphology (histology codes 8000–8140) decreased by 5 percentage points from 1998 (21%) to 2003 (16%). Even if such cases are now being coded as HCC, however, this change can account for only a small portion of the temporal increase, and the variation in trends by age group and race suggests that the increases are not an artifact of better reporting.
Approaches to preventing HCC include primary prevention of viral hepatitis infections and alcohol-related liver disease, secondary prevention of progression to cirrhosis, and prevention of cancer in patients with cirrhosis (37
). A strategy of universal infant vaccination with hepatitis B vaccine, the first vaccine developed to prevent cancer, had been adopted in 150 (78%) of the 192 World Health Organization member states by 2003 (25
). In Taiwan, reductions in HCC incidence were demonstrated after implementation of infant vaccination programs against hepatitis B virus (38
). In the United States, the impact of recommendations from the Advisory Committee on Immunization Practices is reflected in declining hepatitis B incidence, which has been striking since the implementation of universal infant vaccination in 1991 (26
). Many U.S.-born residents and immigrants, however, already have chronic hepatitis B or C virus infections, so these viruses will most likely persist for decades as major causes of HCC. Consequently, support is needed for secondary prevention efforts, which rely on identification of people with chronic viral hepatitis infection or excessive alcohol consumption to allow for appropriate medical management, including counseling and evaluation for antiviral treatment (40
). Furthermore, periodic screening with alpha-fetoprotein and ultrasound has been recommended to promote early detection of HCC among selected populations with evidence of liver disease, but whether this policy results in a reduction in mortality rates has not been evaluated (41
We documented rising HCC incidence rates in the United States during an era in which the overall incidence of cancer has stabilized (42
). The considerable diversity in trends observed among demographic subpopulations most likely reflects differences in primary etiology. As others have observed, over the next decade HCC cases can be expected to continue to increase among people with chronic hepatitis C, but the impact on overall HCC incidence rates is difficult to predict because of limited information on etiology (32
). Similarly, the impact on HCC incidence rates of immigration of people from countries where hepatitis B is endemic will be hard to assess unless more detailed demographic and etiologic data are available. To better characterize HCC trends and guide the planning and evaluation of prevention programs, representative etiologic data are needed to complement the existing system of cancer surveillance in the United States.