The principal findings in this report were that incidence rates of HCC tripled in the United States from 1975 through 2005, with marked recent increases among middle-aged black, Hispanic, and white males; there was a birth-cohort effect on risk; and overall 1-year cause-specific survival rates for new HCC patients nearly doubled from 1992 to 2004 as more patients were diagnosed with low-stage HCC and their prognosis improved. Increases in cause-specific survival rates were experienced by all racial and ethnic groups, except for American Indians/Alaska Natives. However, despite increasing HCC survival rates, improvement is needed, with the 1-year cause-specific survival rate remaining lower than 50%.
Much of the increase in incidence between 2000 and 2005 occurred among men age 50 to 59 years. Not all racial/ethnic groups were equally affected, with black, Hispanic, and white men experiencing the greatest increases. Between 2003 and 2005, for both sexes, blacks in this age group had higher incidence rates than Asian/Pacific Islanders. The changing racial pattern of HCC in this age group may be partially attributable to an epidemic of HCV infection that occurred approximately four decades earlier, in the 1960s, when they were young adults.10
Several findings in this report suggest, however, that risk of HCC is likely to be driven by additional factors. There has been a steady increase in age-adjusted HCC incidence rates among men and women since 1975. Age-specific rates have increased in each successive birth cohort between 1900 and 1959. Etiologic studies of recent HCC patients are recommended to elucidate factors contributing to the ongoing increase in HCC incidence.
In contrast with other racial groups, most Asians/Pacific Islanders with HCC were born outside the United States. This predominance of foreign births is consistent with HBV infection being a major risk factor among most groups of Asians/Pacific Islanders9,20
as chronic HBV infection is notably more common in eastern Asian countries than in the United States, with higher HCC incidence rates among Southeast Asians compared with Filipinos, Japanese, and Asian Indians/Pakistanis.19
An exception is Japan, where more HCC patients are linked to HCV infection than HBV infection.21
The modest increase in HCC incidence rates and decrease in liver cancer mortality rates from 1992 to 2005 suggests that Asians/Pacific Islander populations born in the United States have, thus far, not been as affected by the factors that are driving the HCC increases in other populations. Worldwide, the incidence of HCC among Asians/Pacific Islanders is likely to decline as HBV vaccination becomes more widespread in Asian countries.22
In this study, HCC incidence rates among Hispanics were lower than among Asians/Pacific Islanders, but higher than among whites. Approximately one half of Hispanic HCC patients were born in the United States. In contrast to Asians/Pacific Islanders, HCC incidence rates are reported to be higher among Hispanics born in the United States than among foreign-born Hispanics.23
This suggests that factors associated with life in the United States, perhaps including HCV infection,10
may be adversely affecting Hispanic populations.
Despite a paucity of new therapies for HCC during the surveillance years in this report, 1-year cause-specific survival rates for HCC nearly doubled between 1992 to 1993 and 2003 to 2004. This supports earlier evidence that survival rates for HCC are increasing.26
Initially, the increase in survival was restricted to short-term follow-up27
; however, in this report 4-year survival rates doubled and 5-year survival rates increased by more than 60%. Furthermore, more patients were diagnosed with localized and regional stage HCC and survival rates increased for these patients. With greater awareness of HCC, more patients are being diagnosed with asymptomatic disease via active screening employing serum alpha-fetoprotein testing, abdominal ultrasound, and diagnostic imaging.28
Furthermore, aggressive treatments including transplantation and resection of localized-stage tumors appear to be improving long-term survival.29
The advent of targeted HCC therapies holds promise for further improvement in prognosis among patients with regional and distant-stage HCC.30
Racial variation was seen in 1-year cause-specific survival rates. In 2003 to 2004, survival was greatest among Asians/Pacific Islanders (49%) and lowest among blacks (40%) and American Indians/Alaska Natives (41%). In another study, racial and ethnic variations in survival were partially explained by stage at diagnosis and the therapy received by blacks and Hispanics compared with whites.26
While improvements in survival are needed across all racial and ethnic groups, blacks and American Indians/Alaska Natives may particularly benefit from targeted HCC control efforts.
Coordination of existing HCC prevention efforts is needed. Primary HCC prevention measures include hepatitis B vaccination programs,22
screening of the blood supply for hepatitis viruses,31
and campaigns to discourage intravenous drug abuse. Secondary prevention measures focus on detecting asymptomatic HCC among at-risk individuals28
through periodic screening of high-risk patients by ultrasound, with follow-up tests when suspicious lesions are detected.32
High-risk individuals include cirrhotic patients, adult HBV carriers, and persons infected with HCV. Gaps in HCC screening in the United States include limited HCV testing of current and former injected drug users,33
pre-1990 transfusion recipients,34
and incomplete HBV testing of foreign-born Asians/Pacific Islanders.35
In addition, cultural and economic barriers to HCC screening of chronic viral carriers exist.36,37
Tertiary measures for HCC vary by stage of disease and comorbidity but include surgical resection, transplantation, radiofrequency ablation, and chemoembolization.28
A SEER-Medicare linked study of HCC patients diagnosed in the 1990s indicated that only one third of cases with favorable tumor features received potentially curative therapy.38
A limitation of this study is the absence of information on risk factors. There is a need for studies to estimate the current proportion of HCCs that are attributed to HCV and to HBV including differences across demographic groups.9,39
Studies are needed of the oncogenic potential of viral genotypes.40,41
Associations with suspected cofactors for HCC should also be examined, including alcoholism24
and iron storage diseases.44
This report may underestimate recent increases in HCC incidence rates because of delays in reporting16
and an estimated rate of under-reporting of 2.5% because of absence of data on Veterans' Affairs hospital patients,5
a population which may be at elevated risk for HCC compared with the general population.45
Despite these limitations, the findings strongly suggest that HCC incidence and mortality continue to increase in the United States. In addition, this report provides reason for optimism that, with more HCC screening of high-risk groups and treatment of low-stage disease, the burden of HCC can be lessened.