Epidemiology of Hepatocellular Carcinoma

  • Nubia Muñoz
  • Xavier Bosch


This chapter will deal only with hepatocellular carcinoma (HCC), the most frequent malignant tumor of the liver. Worldwide, HCC is the seventh most common form of cancer in males and the ninth in females [1]. There are variations in its frequency in different geographical areas; thus, it is the most common malignant tumor among males in western, middle, and eastern Africa, the second most common in southern Africa and Southeast Asia, and the third most common among males in China. It is a relatively rare tumor in most parts of America, Europe, northern Africa, and middle and eastern Asia [1].


Hepatocellular Carcinoma HBsAg Carrier Woodchuck Hepatitis Virus World Standard Population Aflatoxin Exposure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Parkin DM, Stjernswärd J, Muir CS (1984) Estimates of the worldwide frequency of twelve major cancers. Bull Wld Hlth Org 62:163–182Google Scholar
  2. 2.
    Parkin DM (ed) (1986) Cancer occurrence in developing countries. International Agency for Research on Cancer, Lyon (IARC Scientific Publications no. 75)Google Scholar
  3. 3.
    Doll R, Payne P, Waterhouse J (eds) (1966) Cancer incidence in five continents. A technical report. Springer, Berlin Heidelberg New YorkGoogle Scholar
  4. 4.
    Doll R, Muir C, Waterhouse J (eds) (1970) Cancer incidence in five continents, vol. II. Springer, Berlin Heidelberg New YorkGoogle Scholar
  5. 5.
    Waterhouse JAH, Muir CS, Correa P, Powell J (eds) (1976) Cancer incidence in five continents, vol. III. International Agency for Research on Cancer, Lyon (IARC Scientific Publications no. 15)Google Scholar
  6. 6.
    Waterhouse JAH, Muir C, Shanmugaratnam K, Powell J (eds) (1982) Cancer incidence in five continents, vol. IV. International Agency for Research on Cancer, Lyon (IARC Scientific Publications no. 42)Google Scholar
  7. 7.
    World Health Organization (1982) World health statistics annual, 1978–1982. Vital statistics and causes of death. WHO, GerevaGoogle Scholar
  8. 8.
    Chinese Academy of Medical Sciences (1981) Atlas of cancer mortality in the People’s Republic of China. China Map Press, BeijingGoogle Scholar
  9. 9.
    Robertson MA, Harington JS, Bradshaw E (1971) The cancer pattern in Africans at Baragwanath Hospital, Johannesburg. Br J Cancer 25: 377–384PubMedCrossRefGoogle Scholar
  10. 10.
    Harington JS, McGlashan ND, Bradshaw E, Geddes EW, Purves LR (1975) A spatial and temporal analysis of four cancers in African gold miners from Southern Africa. Br J Cancer 31: 665–678PubMedCrossRefGoogle Scholar
  11. 11.
    Bradshaw E, McGlashand ND, Fitzgerald D, Harington JS (1982) Analyses of cancer incidence in black gold miners from Southern Africa (1964–79). Br J Cancer 46:737–748PubMedCrossRefGoogle Scholar
  12. 12.
    Van Rensburg SJ, Cook-Mozaffari P, van Schalkwyk DJ, van der Watt JJ, Vincent TJ, Purchase IF (1985) Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei. Br J Cancer 51:713–726PubMedCrossRefGoogle Scholar
  13. 13.
    Shanmugaratnam K, Lee HP, Day NE (eds) (1983) Cancer incidence in Singapore 1968–1977 (IARC Scientific Publications no. 47). International Agency for Research on Cancer, LyonGoogle Scholar
  14. 14.
    Szmuness W (1978) Hepatocellular carcinoma and the hepatitis B virus: evidence for a causal association. Prog Med Virol 24:40–69PubMedGoogle Scholar
  15. 15.
    Muñoz N, Linsell A (1982) Epidemiology of primary liver cancer. In: Correa P, Haenszel W (eds) Epidemiology of cancer of the digestive tract. Nij-hoff, The Hague, pp 161–195CrossRefGoogle Scholar
  16. 16.
    Melbye M, Skinhöj P, Højgaard Nielsen N, Vestergaard BF, Ebbesen P, Hart Hansen JP, Biggar RJ (1984) Virus-associated cancers in Greenland: frequent hepatitis B virus infection but low primary hepatocellular carcinoma incidence. J Natl Cancer Inst 73:1267–1272PubMedGoogle Scholar
  17. 17.
    Prince AM, Szmuness W, Michon J, Desmaille J, Diebolt G, Linhard J, Quenum C, Sankale M (1975) A case-control study of the association between primary liver cancer and hepatitis B infection in Senegal. Int J Cancer 16:376–383PubMedCrossRefGoogle Scholar
  18. 18.
    Kew MC, Desmyter J, Bradburne AF, Macnab GM (1979) Hepatitis B virus infection in southern African blacks with hepatocellular cancer. J Natl Cancer Inst 62: 517–520PubMedGoogle Scholar
  19. 19.
    Lam KC, Yu MC, Leung JWC, Henderson BE (1982) Hepatitis B virus and cigarette smoking: risk factors for hepatocellular carcinoma in Hong Kong. Cancer Res 42: 5246–5248PubMedGoogle Scholar
  20. 20.
    Yeh FS, Mo CC, Luo S, Henderson BE, Tong MJ, Yu MC (1985) A serological case-control study of primary hepatocellular carcinoma in Guangxi, China. Cancer Res 45:872–873PubMedGoogle Scholar
  21. 21.
    Lingao AL, Domingo EO, Nishioka K (1981) Hepatitis B virus profile of hepatocellular carcinoma in the Philippines. Cancer 48:1590–1595PubMedCrossRefGoogle Scholar
  22. 22.
    Trichopoulos D, Day N, Kaklamani E, Tzonou A, Muñoz N, Zavitsanos X, Koumantaki Y, Trichopoulou A (1987) Tobacco smoking, hepatitis B virus and ethanol consumption in the etiology of hepatocellular carcinoma. Int J Cancer (in press)Google Scholar
  23. 23.
    Yarrish RL, Werner BG, Blumberg BS (1980) Association of hepatitis B virus infection with hepatocellular carcinoma in American patients. Int J Cancer, 26:711–715PubMedCrossRefGoogle Scholar
  24. 24.
    Austin H, Delzell E, Grufferman S, Levine R, Morrison AS, Stolley PD, Cole P (1985) A casecontrol study of hepatocellular carcinoma and the hepatitis B virus, cigarette smoking, and alcohol consumption. Cancer Res 46:962–966Google Scholar
  25. 25.
    Beasley R, Lin C, Hwang LY, Chien CS (1981) Hepatocellular carcinoma and hepatitis B virus. A prospective study of 32 707 men in Taiwan. Lancet ii: 1129–1133CrossRefGoogle Scholar
  26. 26.
    Iijima T, Saitoh N, Nobutomo K, Nambu M, Sakuma K (1984) A prospective cohort study of hepatitis B surface antigen carriers in a working population. Gann 75: 571–573Google Scholar
  27. 27.
    Oshima A, Tsukuma H, Hiyama T, Fujimoto I, Yamano H, Tanaka M (1984) Follow-up study of HBs Ag-positive blood donors with special reference to effect of drinking and smoking on development of liver cancer. Int J Cancer 34:775–779PubMedCrossRefGoogle Scholar
  28. 28.
    Prince AM, Alcabes P (1982) The risk of development of hepatocellular carcinoma in hepatitis B virus carriers in New York. A preliminary estimate using death-records matching. Hepatol 2: 15S–20SGoogle Scholar
  29. 29.
    Hall AJ, Winter PD, Wright R (1985) Mortality of hepatitis B positive blood donors in England and Wales. Lancet i: 91–93CrossRefGoogle Scholar
  30. 30.
    Trichopoulos D, Tabor E, Gerety RJ, Xirouchaki E, Sparros L, Muñoz N, Linsell CA (1978) Hepatitis B and primary hepatocellular carcinoma in a European population. Lancet ii: 1217–1219CrossRefGoogle Scholar
  31. 31.
    Szmuness W, Prince AM, Diebolt G, Leblanc L, Baylet R, Masseyeff R, Linhard J (1973) The epidemiology of hepatitis B infections in Africa: results of a pilot survey in the Republic of Senegal. Am J Epidemiol 98:104–110PubMedGoogle Scholar
  32. 32.
    Edman JC, Gray P, Valenzuela P, Rall LB, Rutter WJ (1980) Integration of hepatitis B virus sequences and their expression in a human hepatoma cell line. Nature 286: 535–538PubMedCrossRefGoogle Scholar
  33. 33.
    Shafritz DA, Shouval D, Sherman HI, Hadziyannis SJ, Kew MC (1981) Integration of hepatitis B virus DNA into the genome of liver cells in chronic liver disease and hepatocellular carcinoma. Studies in percutaneous liver biopsies and post-mortem tissue specimens. N Engl J Med 305:1067–1073PubMedCrossRefGoogle Scholar
  34. 34.
    Summers J (1981) Three recently described animal virus models for human hepatitis B virus. Hepatol 1:179–183CrossRefGoogle Scholar
  35. 35.
    Busby WF, Wogan GN (1984) Aflatoxins. In: Searle CE (ed) Chemical carcinogens, 2nd edn. American Chemical Society, Washington, pp 945–1136Google Scholar
  36. 36.
    Sinnhuber RO, Wales JH, Ayres JL, Engebrecht RH, Amend DL (1968) Dietary factors and hepatoma in rainbow trout (Salmo gairdnesi): I. Aflatoxin in vegetable protein foodstuffs. J Natl Cancer Inst 41:711–718PubMedGoogle Scholar
  37. 37.
    Halver JE (1969) Aflatoxin. In: Goldblatt LA (ed) Academic Press, New York, pp 265–306Google Scholar
  38. 38.
    Wogan GN (1973) In: Busch H (ed) Methods in Cancer Res vol 7: Academic Press, New York pp 309–344Google Scholar
  39. 39.
    Wogan GN, Newberne PM (1967) Aflatoxin carcinogenesis. Cancer Res 27:2370–2376PubMedGoogle Scholar
  40. 40.
    Garner C, Ryder R, Montesano R (1985) Monitoring of aflatoxins in human body fluids and application to field studies. Cancer Res 45:922–928Google Scholar
  41. 41.
    Peers FG, Linsell CA (1973) Dietary aflatoxins and liver cancer. A population based study in Kenya. Br J Cancer 27:473–484PubMedCrossRefGoogle Scholar
  42. 42.
    Peers FG, Gilman GA, Linsell CA (1976) Dietary aflatoxins and human liver cancer. A study in Swaziland. Int J Cancer 17:167–176PubMedCrossRefGoogle Scholar
  43. 43.
    Peers FG, Bosch FX, Kaldor JM, Linsell CA (1987) Aflatoxin exposure, hepatitis B virus and liver cancer in Swaziland. Int J Cancer (in press)Google Scholar
  44. 44.
    Shank RC, Gordon JE, Wogan GN, Nondasuta A, Subhamani B (1972) Dietary aflatoxins and human liver cancer: III. Field survey of rural Thai families for ingested aflatoxins. Fd Cosmet Toxicol 10:71–84CrossRefGoogle Scholar
  45. 45.
    Bulatao-Jayme J, Almero EM, Castro CA, Jardeleza TR, Salamat LA (1982) A case-control dietary study of primary liver cancer risk from aflatoxin exposure. Int J Epidemiol 11:112–119PubMedCrossRefGoogle Scholar
  46. 46.
    Garfinkel L (1980) Cancer mortality in nonsmokers. Prospective study by the American Cancer Society. J Natl Cancer Inst 65:1169–1173PubMedGoogle Scholar
  47. 47.
    Hirayama T (1981) A large-scale cohort study on the relationship between diet and selected cancers of digestive organs. In: Bruce WR, Correa P, Lipkin M, Tannenbaum S, Wilkins T (eds) Gastrointestinal cancer: Endogenous factors, Banbury Report 7. CSH Press, Cold Spring Harbor, pp 409-426Google Scholar
  48. 48.
    Trichopoulos D, MacMahon B, Sparros L, Merikas G (1980) Smoking and hepatitis B-negative primary hepatocellular carcinoma. J Natl Cancer Inst 65:111–114PubMedGoogle Scholar
  49. 49.
    Yu MC, Mack T, Hanisch R, Peters RL, Henderson BE, Pike MC (1983) Hepatitis, alcohol consumption, cigarette smoking, and hepatocellular carcinoma in Los Angeles. Cancer Res 43:6077–6079PubMedGoogle Scholar
  50. 50.
    Hardell L, Bengtsson NO, Jonsson U, Eriksson S, Larsson LG (1984) Aetiological aspects on primary liver cancer with special regard to alcohol, organic solvents and acute intermittent porphyria —an epidemiological investigation. Br J Cancer 50: 389–397PubMedCrossRefGoogle Scholar
  51. 51.
    Stemhagen A, Slade J, Altman R, Bill J (1983) Occupational risk factors and liver cancer. A retrospective case-control study of primary liver cancer in New Jersey. Am J Epidemiol 117:443–454PubMedGoogle Scholar
  52. 52.
    Austin H, Delzell E, Grufferman S, Levine R, Morrison AS, Stolley PD, Cole P (1986) A casecontrol study of hepatocellular carcinoma and the hepatitis B virus, cigarette smoking, and alcohol consumption. Cancer Res 46:962–966PubMedGoogle Scholar
  53. 53.
    Anthony PP (1976) Pathology of hepatocellular carcinoma. In: Cameron HM, Linsell CA, Warwick GP (eds) Liver cell cancer Elsevier, Amsterdam, pp 93–120Google Scholar
  54. 54.
    Tuyns A (1980) Alcohol. In: Schottenfeld D, Fraumeni JF (eds) Cancer epidemiology and prevention. Saunders, Philadelphia, pp 293–303Google Scholar
  55. 55.
    Rothman KJ (1980) The proportion of cancer attributable to alcohol consumption. Prev Med 9:174–179PubMedCrossRefGoogle Scholar
  56. 56.
    Obata H, Hayashi N, Motoike Y, Hisamitsu T, Okuda H, Koibayashi S, Nishioka K (1980) A prospective study on the development of hepatocellular carcinoma from liver cirrhosis with persistent hepatitis B virus infection. Int J Cancer 25: 741–747PubMedCrossRefGoogle Scholar
  57. 57.
    Zaman SN, Melia WM, Johnson RD, Portmann BC, Johnson PJ, Williams R (1985) Risk factors in development of hepatocellular carcinoma in cirrhosis: prospective study of 613 patients. Lancet ii: 1357–1360CrossRefGoogle Scholar
  58. 58.
    Lieber CS, Seitz HK, Garro AJ, Worner TM (1979) Alcohol-related diseases and carcinogenesis. Cancer Res 39:2863–2866PubMedGoogle Scholar
  59. 59.
    Brechot C, Nalpas B, Courouce AM, Duhamel G, Callard P, Carnot F, Tiollais P, Bethelot P (1982) Evidence that hepatitis B virus has a role in livercell carcinoma in alcoholic liver disease. N Engl J Med 306:1384–1387PubMedCrossRefGoogle Scholar
  60. 60.
    Hino O, Kitagawa T, Sugano H (1985) Relationship between serum and histochemical markers for hepatitis B virus and rate of viral integration in hepatocellular carcinomas in Japan. Int J Cancer 35:5–10PubMedCrossRefGoogle Scholar
  61. 61.
    Jick H, Herman R (1978) Oral contraceptiveinduced benign liver tumors. The magnitude of the problem. J Am Med Assoc 240:828–829CrossRefGoogle Scholar
  62. 62.
    Guy JT, Smith RE (1980) Androgens and hepatocellular carcinoma. In: Nieburgs HE (ed) Prevention and detection of cancer, part II: Detection, vol. 2: Cancer detection in specific sites. Marcel Dekker, New York, pp 217–285Google Scholar
  63. 63.
    Nakashima T, Okuda K, Kajino M, Sakamoto K, Kubo Y, Shimokawa Y (1975) Primary liver cancer coincident with schistosomiasis japonica. Cancer 36:1483–1489PubMedCrossRefGoogle Scholar
  64. 64.
    Inaba Y, Maruchi N, Matsuda M, Yoshihara N, Yamamoto SI (1984) A case-control study on liver cancer with special emphasis on the possible aetiological role of schistosomiasis. Int J Epidemiol 13:408–412PubMedCrossRefGoogle Scholar
  65. 65.
    Battifora HA (1976) Thorotrast and tumours of the liver. In: Okuda K, Peters RL (eds) Hepatocellular carcinoma. Wiley, New York, pp 83–93Google Scholar
  66. 66.
    Okuda K, Mackay I (eds) (1982) Hepatocellular carcinoma. International Union Against Cancer, Geneva (UICC Technical Report Series vol. 74)Google Scholar
  67. 67.
    Leblanc L, Tuyns AJ, Masseyeff R (1973) Screening for primary liver cancer. Digestion 8: 8–14PubMedCrossRefGoogle Scholar
  68. 68.
    Maupas P, Chiron JP, Barin F, Coursaget P, Goudeau A, Perrin J, Denis F, Diop Mar I (1981) Efficacy of hepatitis B vaccine in prevention of early HBsAg carrier state in children. Controlled trial in an endemic area (Senegal). Lancet i: 289–292CrossRefGoogle Scholar
  69. 69.
    Szmuness W, Stevens CE, Harley EJ, Zang EA, Oleszko WR, William DC, Sadovsky R, Morrison JM, Kellner A (1980) Hepatitis B vaccine. Demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med 303:833–841PubMedCrossRefGoogle Scholar
  70. 70.
    Beasley RP, Hwang LY, Stevens CE, Lin CC, Hsieh FJ, Wang KY, Sun TS, Szmuness W (1983) Efficacy of hepatitis B immune globulin for prevention of perinatal transmission of the hepatitis B virus carrier state: final report of a randomized double-blind, placebo-controlled trial. Hepatol 3:135–141CrossRefGoogle Scholar
  71. 71.
    IARC (1984) Annual Report. International Agency for Research on Cancer, Lyon, pp 50-51Google Scholar
  72. 72.
    World Health Organization (1983) Prevention of Liver Cancer (Technical Report Series vol. 691). World Health Organization, GenevaGoogle Scholar

Copyright information

© Springer Japan 1987

Authors and Affiliations

  • Nubia Muñoz
  • Xavier Bosch
    • 1
  1. 1.International Agency for Research on CancerLyon Cedex 08France

Personalised recommendations