Tumor Biology

, Volume 35, Issue 1, pp 567–572 | Cite as

Association of Kaposi’s sarcoma-associated herpesvirus (KSHV) with bladder cancer in Croatian patients

  • Martina Paradžik
  • Viljemka Bučević-Popović
  • Marijan Šitum
  • Crystal J. Jaing
  • Marina Degoricija
  • Kevin S. McLoughlin
  • Said I. Ismail
  • Volga Punda-Polić
  • Janoš Terzić
Research Article


As the seventh most common human malignancy, bladder cancer represents a global health problem. In addition to well-recognized risk factors such as smoking and exposure to chemicals, various infectious agents have been implicated as cofactors in the pathogenesis of urothelial malignancies. The aim of the present study was to assess the possible association of viral infection and bladder cancer in Croatian patients. Biopsy specimens were collected from a total of 55 patients diagnosed with different stages of bladder cancer. Initial screening of DNA extracts for the presence of viruses on Lawrence Livermore Microbial Detection Array revealed Kaposi’s sarcoma-associated herpesvirus (KSHV) in each of three randomly chosen biopsy specimens. The prevalence of infection with KSHV among study population was then examined by KSHV-specific polymerase chain reaction (PCR) and immunoblotting. By nested PCR, KSHV DNA was detected in 55 % of patients. KSHV, also known as human herpesvirus 8, is an infectious agent known to cause cancer. Its oncogenic potential is primarily recognized from its role in Kaposi’s sarcoma, but it has also been involved in pathogenesis of two lymphoproliferative disorders. A high prevalence of KSHV infection in our study indicates that KSHV may play a role in tumorigenesis of bladder cancer and warrants further studies.


Bladder cancer Human herpesvirus 8 Kaposi’s sarcoma-associated herpesvirus Microarray 


  1. 1.
    Bray F, Jian-Song R, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013;132:1133–45.PubMedCrossRefGoogle Scholar
  2. 2.
    Croatian National Institute of Public Health. Croatian health service yearbook 2011. http://www.hzjz.hr/publikacije/hzs_ljetopis/Ljetopis_Yearbook_HR_2011.pdf. Accessed 18 Mar 2013.
  3. 3.
    International Agency for Research on Cancer. Cancer site by site. In: Boyle P, Levin B (eds). World cancer report 2008. http://www.iarc.fr/en/publications/pdfs-online/wcr/2008/wcr_2008_7.pdf. Accessed 18 Mar 2013.
  4. 4.
    Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet. 2009;374:239–49.PubMedCrossRefGoogle Scholar
  5. 5.
    Alibek K, Karatayeva N, Bekniyazov I. The role of infectious agents in urogenital cancers. Infect Agent Cancer. 2012;7:35. doi:10.1186/1750-9378-7-35.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Fried B, Reddy A, Mayer D. Helminths in human carcinogenesis. Cancer Lett. 2011;305:239–49.PubMedCrossRefGoogle Scholar
  7. 7.
    Bedwani R, Renganathan E, El Kwhskyl F, Braga C, Abu Seif HH, Amul Azm T, et al. Schistosomiasis and the risk of bladder cancer in Alexandria. Egypt Br J Cancer. 1998;77:1186–9.CrossRefGoogle Scholar
  8. 8.
    Zaghloul MS. Bladder cancer and schistosomiasis. J Egypt Natl Cancer Inst. 2012;24:151–9.CrossRefGoogle Scholar
  9. 9.
    Barghi MR, Hajimohammadmehdiarbab A, Moghaddam SM, Kazemi B. Correlation between human papillomavirus infection and bladder transitional cell carcinoma. BMC Infect Dis. 2005;5:102.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Li N, Yang L, Zhang Y, Zhao P, Zheng T, Dai M. Human papillomavirus infection and bladder cancer risk: a meta-analysis. J Infect Dis. 2011;204:217–23.PubMedCrossRefGoogle Scholar
  11. 11.
    Alexiev BA, Randhawa P, Vazquez Martul E, Zeng G, Luo C, Ramos E, et al. BK virus-associated urinary bladder carcinoma in transplant recipients: report of 2 cases, review of the literature, and proposed pathogenic model. Hum Pathol. 2013;44(5):908–17. doi:10.1016/j.humpath.2012.09.019.PubMedCrossRefGoogle Scholar
  12. 12.
    Badawi H, Ahmed H, Aboui Fadi L, Helmi A, Fam N, Diab M, et al. Herpes simplex virus type-2 in Egyptian patients with bladder cancer of cystitis. APMIS. 2009;118:37–44.CrossRefGoogle Scholar
  13. 13.
    Escudero AL, Luque RJ, Quintero A, Alvarez-Kindelan J, Requena MJ, Montironi R, et al. Association of human herpesvirus type 6 DNA with human bladder cancer. Cancer Lett. 2005;230:20–4.PubMedCrossRefGoogle Scholar
  14. 14.
    Monini P, De Lelis L, Fabris M, Rigolin F, Cassai E. Kaposi’s sarcoma-associated herpesvirus DNA sequences in prostate tissue and human semen. N Engl J Med. 1996;334:1168–72.PubMedCrossRefGoogle Scholar
  15. 15.
    Panagiotakis GI, Papadogianni D, Chatziioannou MN, Lasithiotaki I, Delakas D, Spandidos DA. Association of human herpes, papilloma and polyoma virus families with bladder cancer. Tumor Biol. 2013;34:71–9.CrossRefGoogle Scholar
  16. 16.
    Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science. 1994;266:1865–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Cohen A, Wolf DG, Guttman-Yassky E, Sarid R. Kaposi’s sarcoma-associated herpesvirus: clinical, diagnostic, and epidemiological aspects. Crit Rev Clin Lab Sci. 2005;42:101–53.PubMedCrossRefGoogle Scholar
  18. 18.
    Wen KW, Damania B. Kaposi sarcoma-associated herpesvirus (KSHV): molecular biology and oncogenesis. Cancer Lett. 2010;289:140–50.PubMedCrossRefGoogle Scholar
  19. 19.
    Bechtel JT, Liang Y, Hvidding J, Ganem D. Host range of Kaposi’s sarcoma-associated herpesvirus in cultured cells. J Virol. 2003;77:6474–81.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Cai Q, Verma SC, Lu J, Robertson ES. Molecular biology of Kaposi’s sarcoma herpesvirus and related oncogenesis. Adv Virus Res. 2010;78:87–142.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    De Oliveira DE, Ballon G, Cesarman E. NF-κB signaling modulation by EBV and KSHV. Trends Microbiol. 2010;18:248–57.PubMedCrossRefGoogle Scholar
  22. 22.
    Ganem D. KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine. J Clin Investig. 2010;120:939–49.PubMedCrossRefGoogle Scholar
  23. 23.
    Cattani P, Cerimele F, Porta D, Graffeo R, Ranno S, Marchetti S, et al. Age-specific seroprevalence of human herpesvirus 8 in Mediterranean regions. Clin Microbiol Infect. 2003;9:274–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Mesri EA, Cesarman E, Boshoff C. Kaposi’s sarcoma and its associated herpesvirus. Nat Rev Cancer. 2010;10:707–19.PubMedCrossRefGoogle Scholar
  25. 25.
    Gardner SN, Jaing CJ, McLoughlin KS, Slezak TR. A microbial detection array (MDA) for viral and bacterial detection. BMC Genomics. 2010;11:668.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Erlandsson L, Rosenstierne MW, Jaing C, McLoughlin K, Gardner S, Fomsgaard A. The microbial detection array combined with random Phi29 amplification used as a diagnostic tool for unbiased virus detection in clinical samples. PLoS One. 2011;6:e22631.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Pan L, Milligan L, Michaeli J, Cesarman E, Knowles DM. Polymerase chain reaction detection of Kaposi’s sarcoma-associated herpesvirus-optimized protocols and their application to myeloma. J Mol Diagn. 2001;3:32–8.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Ben-Neriah Y, Karin M. Inflammation meets cancer, with NF-κB as the matchmaker. Nat Immunol. 2011;12:715–23.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Martina Paradžik
    • 1
  • Viljemka Bučević-Popović
    • 2
  • Marijan Šitum
    • 3
  • Crystal J. Jaing
    • 4
  • Marina Degoricija
    • 1
  • Kevin S. McLoughlin
    • 4
  • Said I. Ismail
    • 5
  • Volga Punda-Polić
    • 1
  • Janoš Terzić
    • 1
  1. 1.School of MedicineUniversity of SplitSplitCroatia
  2. 2.Department of Chemistry, Faculty of ScienceUniversity of SplitSplitCroatia
  3. 3.Department of UrologyClinical Hospital SplitSplitCroatia
  4. 4.Global Security, Lawrence Livermore National LaboratoryLivermoreUSA
  5. 5.Molecular Biology Research Lab, Department of Biochemistry, Faculty of MedicineUniversity of JordanAmmanJordan

Personalised recommendations