Journal of the National Cancer Institute Advance Access originally published online on September 16, 2009
JNCI Journal of the National Cancer Institute 2009 101(19):1348-1355; doi:10.1093/jnci/djp288
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© The Author 2009. Published by Oxford University Press.
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Decreased Incidence of Hepatocellular Carcinoma in Hepatitis B Vaccinees: A 20-Year Follow-up Study
Affiliations of authors: Department of Pediatrics (M-HC) and Graduate Institute of Clinical Medicine (C-JL, D-SC), College of Medicine, and Graduate Institute of Epidemiology (S-LY, C-JC), College of Public Health, National Taiwan University, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan (S-LY, C-JC); Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, College of Medicine, Chang Gung University, Kaohsiung, Taiwan (C-ML); Liver Research Unit, Chang Gung University and Hospital, Linkou, Taiwan (S-ML); Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan (H-CC); Division of Gastroenterology, Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan (T-CW); Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan (S-SY); Department of Health, Center for Disease Control, Taipei, Taiwan (H-SK)
Correspondence to: Mei-Hwei Chang, MD, Department of Pediatrics, National Taiwan University Hospital, Chung-Shan S. Road, Taipei, Taiwan (e-mail: changmh{at}ntu.edu.tw).
Background: Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma. This population-based study aimed to investigate whether prevention of hepatocellular carcinoma by the universal Taiwanese HBV vaccine program, launched in July 1984, has extended beyond childhood and to identify the predictors of hepatocellular carcinoma for vaccinated birth cohorts.
Methods: Data on 1958 patients with hepatocellular carcinoma who were aged 6–29 years at diagnosis in Taiwan between 1983 and 2004 were collected from two national hepatocellular carcinoma registries. Age- and sex-specific incidence among vaccinated and unvaccinated birth cohorts were analyzed by using Poisson regression models. All statistical tests were two-sided. Records of 64 hepatocellular carcinoma patients and 5 524 435 HBV vaccinees who were born after the initiation of the vaccination program were compared for HBV immunization characteristics during infancy and prenatal maternal hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) serostatus.
Results: Hepatocellular carcinoma incidence was statistically significantly lower among children aged 6–19 years in vaccinated compared with unvaccinated birth cohorts (64 hepatocellular cancers among vaccinees in 37 709 304 person-years vs 444 cancers in unvaccinated subjects in 78 496 406 person-years, showing an age- and sex-adjusted relative risk of 0.31, P < .001, for persons vaccinated at birth). The risk of developing hepatocellular carcinoma for vaccinated cohorts was statistically significantly associated with incomplete HBV vaccination (for those who received fewer than three doses of HBV vaccine, odds ratio [OR] = 4.32, 95% confidence interval [CI] = 2.34 to 7.91); with prenatal maternal HBsAg seropositivity (OR = 29.50, 95% CI = 13.98 to 62.60); with prenatal maternal HBeAg seropositivity (with administration of hepatitis B immunoglobulin at birth, OR = 5.13, 95% CI = 2.24 to 11.71; and without it, OR = 9.43, 95% CI = 3.54 to 25.11).
Conclusion: The prevention of hepatocellular carcinoma by this HBV vaccine extends from childhood to early adulthood. Failure to prevent hepatocellular carcinoma results mostly from unsuccessful control of HBV infection by highly infectious mothers.
| CONTEXT AND CAVEATS Prior knowledge A universal hepatitis B virus vaccination program was initiated in July 1984 in Taiwan. Vaccinated children have been followed through adolescence to adulthood to determine the effectiveness of the vaccine in prevention of hepatocellular carcinoma. Study design Incidence of hepatocellular carcinoma in Taiwan from 1983 to 2004 was ascertained from two national cancer registries, and age- and sex-specific incidence were compared among vaccinated and unvaccinated birth cohorts with regression models. Characteristics of the 64 children who were vaccinated and developed hepatocellular carcinoma were also analyzed. Contribution Incidence of hepatocellular carcinoma was statistically significantly reduced among individuals who were aged 6–19 years in postvaccine vs prevaccine birth cohorts. Vaccinated individuals who still developed this cancer were likely to have been insufficiently dosed or to have been born to hepatitis B virus–seropositive mothers. Implications Properly administered, the effectiveness of the hepatitis B virus vaccine appears to extend into early adulthood. Limitations This study did not examine other possible risk factors for the development of hepatocellular carcinoma. From the Editors
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Manuscript received December 1, 2008; revised July 6, 2009; accepted July 24, 2009.
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