Medical Microbiology and Immunology

, Volume 192, Issue 3, pp 137–140 | Cite as

Esophageal cancer in Germany is associated with Epstein-Barr-virus but not with papillomaviruses

  • S. AwerkiewEmail author
  • E. Bollschweiler
  • R. Metzger
  • P. M. Schneider
  • A. H. Hölscher
  • H. Pfister
Original Investigation


Esophageal squamous cell carcinomas (n=23) and adenocarcinomas (n=14) from German patients were tested for the presence of human papillomavirus (HPV) and Epstein-Barr-Virus (EBV) DNA. No DNA for either genital HPV or epidermodysplasia verruciformis-associated HPV was detected in any tumor. In contrast, 35% of squamous cell carcinomas and 36% of adenocarcinomas were shown to contain EBV DNA by nested polymerase chain reaction.


Esophageal cancer Human Papillomavirus Epstein-Barr Virus 


  1. 1.
    Berkhout RJ, Tieben LM, Smits HL, Bavinck JN, Vermeer BJ, Schegget J ter (1995) Nested PCR approach for detection and typing of epidermodysplasia verruciformis-associated human papillomavirus types in cutaneous cancers from renal transplant recipients. J Clin Microbiol 33:690–695Google Scholar
  2. 2.
    Bjorge T, Dillner J, Anttila T, Engeland A, Hakulinen T, Jellum E, Lehtinen M, Luostarinen T, Paavonen J, Pukkala E, Sapp M, Schiller J, Youngman L, Thoresen S (1997) Prospective seroepidemiological study of role of human papillomavirus in non-cervical anogenital cancers. BMJ 315:646–649Google Scholar
  3. 3.
    Bollschweiler E, Hölscher AH (2000) Rising incidence of esophageal adenocarcinoma. Dtsch Ärzteblatt 27:1595–1598Google Scholar
  4. 4.
    Bollschweiler E, Wolfgarten E, Gutschow C, Holscher AH (2001) Demographic variations in the rising incidence of esophageal adenocarcinoma in white males. Cancer 92:549–555Google Scholar
  5. 5.
    Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV (1995) Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 87:796–802Google Scholar
  6. 6.
    Chang F, Syrjanen S, Shen Q, Ji HX, Syrjanen K (1990) Human papillomavirus (HPV) DNA in esophageal precancer lesions and squamous cell carcinomas from China. Int J Cancer 45:21–25Google Scholar
  7. 7.
    Chen B, Yin H, Dhurandhar N (1994) Detection of human papillomavirus DNA in esophageal squamous cell carcinomas by the polymerase chain reaction using general consensus primers. Hum Pathol 25:920–923Google Scholar
  8. 8.
    De Roda Husman AM, Walboomers JM, Brule AJ van den, Meijer CJ, Snijders PJ (1995) The use of general primers GP5 and GP6 elongated at their 3' ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 76:1057–1062Google Scholar
  9. 9.
    De Villiers EM, Lavergne D, Chang F, Syrjanen K, Tosi P, Cintorino M, Santopietro R, Syrjanen S (1999) An interlaboratory study to determine the presence of human papillomavirus DNA in esophageal carcinoma from China. Int J Cancer 81:225–228Google Scholar
  10. 10.
    Gärtner B, Schäfer H, Marggraff K, Eisele G, Schäfer M, Roemer K, Laws H, Sester M, Sester U, Eisele H, Mueller-Lantzsch N (2002) Evaluation of use of Epstein-Barr viral load in patients after allogeneic stem cell transplantation to diagnose and monitor posttransplant lymphoproliferative disease. J Clin Microbiol 40:351–358Google Scholar
  11. 11.
    Han C, Qiao G, Hubbert NL, Li L, Sun C, Wang Y, Yan M, Xu D, Li Y, Lowy DR, Schiller JT (1996) Serologic association between human papillomavirus type 16 infection and esophageal cancer in Shaanxi Province, China. J Natl Cancer Inst 88:1467–1471Google Scholar
  12. 12.
    He D, Zhang DK, Lam KY, Ma L, Ngan HY, Liu SS, Tsao SW (1997) Prevalence of HPV infection in esophageal squamous cell carcinoma in Chinese patients and its relationship to the p53 gene mutation. Int J Cancer 72:959–964Google Scholar
  13. 13.
    Hong T, Shimada Y, Kano M, Kaganoi J, Uchida S, Komoto I, Yamabe H, Imamura M (2000) The Epstein-Barr virus is rarely associated with esophageal cancer. Int J Mol Med 5:363–368Google Scholar
  14. 14.
    IARC (1995) Monographs on the evaluation of carcinogenic risks to humans, vol 64: Human papillomaviruses. IARC, LyonGoogle Scholar
  15. 15.
    Jager M, Prang N, Mitterer M, Larcher C, Huemer HP, Reischl U, Wolf H, Schwarzmann F (1996) Pathogenesis of chronic Epstein-Barr virus infection: detection of a virus strain with a high rate of lytic replication. Br J Haematol 95:626–636Google Scholar
  16. 16.
    Jenkins TD, Nakagawa H, Rustgi AK (1996) The association of Epstein-Barr virus DNA with esophageal squamous cell carcinoma. Oncogene 13:1809–1813Google Scholar
  17. 17.
    Khurshid A, Kazuya N, Hanae I, Manabu I (1998) Infection of human papillomavirus (HPV) and Epstein-Barr virus (EBV) and p53 expression in human esophageal carcinoma. J Pak Med Assoc 48:138–142Google Scholar
  18. 18.
    Kijima Y, Hokita S, Takao S, Baba M, Natsugoe S, Yoshinaka H, Aridome K, Otsuji T, Itoh T, Tokunaga M, Eizuru Y, Aikou T (2001) Epstein-Barr virus involvement is mainly restricted to lymphoepithelial type of gastric carcinoma among various epithelial neoplasms. J Med Virol 64:513–518Google Scholar
  19. 19.
    Kjaerheim K, Gaard M, Andersen A (1998) The role of alcohol, tobacco, and dietary factirs in upper aerogastric tract cancers: a prospective study of 10,900 Norwegian men. Cancer Causes Control 9:99–105Google Scholar
  20. 20.
    Klussmann JP, Weissenborn S, Wieland U, Dries V, Kolligs J, Jungenhuelsing M, Eckel H, Dienes H, Pfister H, Fuchs PG (2001) Prevalence, distributation, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. Cancer 92:2875–2884Google Scholar
  21. 21.
    Kulski JK, Demeter T, Mutavdzic S, Sterrett GF, Mitchell KM, Pixley EC (1990) Survey of histologic specimens of human cancer for human papillomavirus types 6/11/16/18 by filter in situ hybridization. Am J Clin Pathol 94:566–570Google Scholar
  22. 22.
    Lagergren J, Bergstrom R, Lindgren A, Nyren O (1999) Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 340:825–831Google Scholar
  23. 23.
    Lagergren J, Bergström R, Nyren O (1999) Assotiation between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann Intern Med 130:883–889Google Scholar
  24. 24.
    Lagergren J, Wang Z, Bergstrom R, Dillner J, Nyren O (1999) Human papillomavirus infection and esophageal cancer: a nationwide seroepidemiologic case-control study in Sweden. J Natl Cancer Inst 91:156–162Google Scholar
  25. 25.
    Lambot MA, Peny MO, Noel JC (1998) Human papillomavirus infection in esophageal squamous cell carcinoma in Belgium. Hum Pathol 29:1175–1176Google Scholar
  26. 26.
    Lavergne D, Villiers EM de (1999) Papillomavirus in esophageal papillomas and carcinomas. Int J Cancer 80:681–684Google Scholar
  27. 27.
    Miller BA, Davidson M, Myerson D, Icenogle J, Lanier AP, Tan J, Beckmann AM (1997) Human papillomavirus type 16 DNA in esophageal carcinomas from Alaska Natives. Int J Cancer 71:218–222Google Scholar
  28. 28.
    Morgan RJ, Perry AC, Newcomb PV, Hardwick RH, Alderson D (1997) Human papillomavirus and oesophageal squamous cell carcinoma in the UK. Eur J Surg Oncol 23:513–517Google Scholar
  29. 29.
    Mori M, Watanabe M, Tanaka S, Mimori K, Kuwano H, Sugimachi K (1994) Epstein-Barr virus-associated carcinomas of the esophagus and stomach. Arch Pathol Lab Med 118:998–1001Google Scholar
  30. 30.
    Parkin DM, Pisani P, Ferlay J (1993) Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 54:594–606Google Scholar
  31. 31.
    Poljak M, Cerar A, Seme K (1998) Human papillomavirus infection in esophageal carcinomas: a study of 121 lesions using multiple broad-spectrum polymerase chain reactions and literature review. Hum Pathol 29:266–271Google Scholar
  32. 32.
    Saegusa M, Hashimura M, Takano Y, Ohbu M, Okayasu I (1997) Absence of human papillomavirus genomic sequences detected by the polymerase chain reaction in oesophageal and gastric carcinomas in Japan. Mol Pathol 50:101–104Google Scholar
  33. 33.
    Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N (1985) Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354Google Scholar
  34. 34.
    Shen Z, Cen S, Shen J, Cai W, Xu J, Teng Z, Hu Z, Zeng Y (2000) Study of immortalization and malignant transformation of human embryonic esophageal epithelial cells induced by HPV18 E6E7. J Cancer Res Clin Oncol 126:589–594Google Scholar
  35. 35.
    Smits HL, Tjong AHSP, Schegget J ter, Nooter K, Kok T (1995) Absence of human papillomavirus DNA from esophageal carcinoma as determined by multiple broad spectrum polymerase chain reactions. J Med Virol 46:213–215Google Scholar
  36. 36.
    Terry P, Lagergren J, Ye W, Wolk A, Nyren O (2001) Inverse association between intake of cereal fiber and risk of gastric cardia cancer. Gastroenterology 120:387–391Google Scholar
  37. 37.
    Togawa K, Jaskiewicz K, Takahashi H, Meltzer SJ, Rustgi AK (1994) Human papillomavirus DNA sequences in esophagus squamous cell carcinoma. Gastroenterology 107:128–136Google Scholar
  38. 38.
    Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19Google Scholar
  39. 39.
    Wang J, Noffsinger A, Stemmermann G, Fenoglio-Preiser C (1999) Esophageal squamous cell carcinomas arising in patients from a high-risk area of North China lack an association with Epstein-Barr virus. Cancer Epidemiol Biomarkers Prev 8:1111–1114Google Scholar
  40. 40.
    Wang LS, Chow KC, Wu YC, Li WY, Huang MH (1999) Detection of Epstein-Barr virus in esophageal squamous cell carcinoma in Taiwan. Am J Gastroenterol 94:2834–2839Google Scholar
  41. 41.
    West AB, Soloway GN, Lizarraga G, Tyrrell L, Longley JB (1996) Type 73 human papillomavirus in esophageal squamous cell carcinoma: a novel association. Cancer 77:2440–2444Google Scholar
  42. 42.
    Wieland U, Jurk S, Weissenborn S, Krieg T, Pfister H, Ritzkowsky A (2000) Erythroplasia of Queyrat: coinfection with cutaneous carcinogenic human papillomavirus type 8 and genital papillomaviruses in a carcinoma in situ. J Invest Dermatol 115:396–401Google Scholar
  43. 43.
    Wolfgarten E, Rosendahl U, Nowroth U, Leers J, Metzger R, Holscher AH, Bollschweiler E (2001) Coincidence of nutritional habits and esophageal cancer in Germany. Oncologie 24:546–551Google Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • S. Awerkiew
    • 1
    Email author
  • E. Bollschweiler
    • 2
  • R. Metzger
    • 2
  • P. M. Schneider
    • 2
  • A. H. Hölscher
    • 2
  • H. Pfister
    • 1
  1. 1.Institute of Virology, University of Cologne, Fürst-Pückler Str. 56, 50935 Cologne, Germany
  2. 2.Department of Surgery, University of Cologne, Cologne, Germany

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