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. 2001 Sep 1;85(9):1298–1303. doi: 10.1054/bjoc.2001.2052

Cancers associated with Kaposi's sarcoma (KS) in AIDS: a link between KS herpesvirus and immunoblastic lymphoma

E A Engels 1, P S Rosenberg 2, M Frisch 1,3, J J Goedert 1
PMCID: PMC2375238  PMID: 11720464

Abstract

Kaposi's sarcoma (KS), common among persons with acquired immunodeficiency syndrome (AIDS), is caused by KS herpesvirus (KSHV) but whether KSHV causes other malignancies is uncertain. Using linked United States AIDS and cancer registries, we measured the incidence of specific malignancies in persons with AIDS (4–27 months after AIDS onset). We identified associations with KSHV by calculating a relative risk: cancer incidence in persons with KS (all were KSHV-infected) divided by incidence in persons without KS. Using Poisson regression, relative risks were adjusted for human immunodeficiency virus risk group, gender, age, race, and calendar year. We included 189 159 subjects (26 972 with KS). Immunoblastic lymphoma was significantly associated with KS (506 cases; relative risks: unadjusted 2.44, 95%CI 2.00–2.96, adjusted 1.58, 95%CI 1.29–1.93). Only one immunoblastic lymphoma had pleura as primary site. None of 37 other specified malignancies (other non-Hodgkin lymphomas, haematological malignancies, solid tumours) was significantly associated with KS. In summary, the association of immunoblastic lymphoma with KS was specific among examined malignancies and remained significant after statistical adjustment. Our findings, and the previously demonstrated presence of KSHV in the histologically related primary effusion lymphoma, suggest that KSHV is involved in the pathogenesis of some immunoblastic lymphomas. © 2001 Cancer Research Campaign

Keywords: Kaposi's sarcoma, non-Hodgkin lymphoma, acquired immunodeficiency syndrome (AIDS), human immunodeficiency virus (HIV), Kaposi's sarcoma herpesvirus (KSHV) also known as human herpesvirus 8

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Selected References

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  1. Antman K., Chang Y. Kaposi's sarcoma. N Engl J Med. 2000 Apr 6;342(14):1027–1038. doi: 10.1056/NEJM200004063421407. [DOI] [PubMed] [Google Scholar]
  2. Berenson J. R., Vescio R. A. HHV-8 is present in multiple myeloma patients. Blood. 1999 May 15;93(10):3157–3166. [PubMed] [Google Scholar]
  3. Biggar R. J., Curtis R. E., Cote T. R., Rabkin C. S., Melbye M. Risk of other cancers following Kaposi's sarcoma: relation to acquired immunodeficiency syndrome. Am J Epidemiol. 1994 Feb 15;139(4):362–368. doi: 10.1093/oxfordjournals.aje.a117008. [DOI] [PubMed] [Google Scholar]
  4. Blackbourn D. J., Ambroziak J., Lennette E., Adams M., Ramachandran B., Levy J. A. Infectious human herpesvirus 8 in a healthy North American blood donor. Lancet. 1997 Mar 1;349(9052):609–611. doi: 10.1016/S0140-6736(96)10004-0. [DOI] [PubMed] [Google Scholar]
  5. Cesarman E., Chang Y., Moore P. S., Said J. W., Knowles D. M. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med. 1995 May 4;332(18):1186–1191. doi: 10.1056/NEJM199505043321802. [DOI] [PubMed] [Google Scholar]
  6. Cesarman E., Knowles D. M. The role of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in lymphoproliferative diseases. Semin Cancer Biol. 1999 Jun;9(3):165–174. doi: 10.1006/scbi.1998.0118. [DOI] [PubMed] [Google Scholar]
  7. Dupin N., Diss T. L., Kellam P., Tulliez M., Du M. Q., Sicard D., Weiss R. A., Isaacson P. G., Boshoff C. HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma. Blood. 2000 Feb 15;95(4):1406–1412. [PubMed] [Google Scholar]
  8. Engels E. A., Whitby D., Goebel P. B., Stossel A., Waters D., Pintus A., Contu L., Biggar R. J., Goedert J. J. Identifying human herpesvirus 8 infection: performance characteristics of serologic assays. J Acquir Immune Defic Syndr. 2000 Apr 1;23(4):346–354. doi: 10.1097/00126334-200004010-00011. [DOI] [PubMed] [Google Scholar]
  9. Frisch M., Biggar R. J., Engels E. A., Goedert J. J., AIDS-Cancer Match Registry Study Group Association of cancer with AIDS-related immunosuppression in adults. JAMA. 2001 Apr 4;285(13):1736–1745. doi: 10.1001/jama.285.13.1736. [DOI] [PubMed] [Google Scholar]
  10. Gessain A., Brière J., Angelin-Duclos C., Valensi F., Béral H. M., Davi F., Nicola M. A., Sudaka A., Fouchard N., Gabarre J. Human herpes virus 8 (Kaposi's sarcoma herpes virus) and malignant lymphoproliferations in France: a molecular study of 250 cases including two AIDS-associated body cavity based lymphomas. Leukemia. 1997 Feb;11(2):266–272. doi: 10.1038/sj.leu.2400549. [DOI] [PubMed] [Google Scholar]
  11. Gérard L., Agbalika F., Sheldon J., Maillard A., Schulz T. F., Oksenhendler E. No increased human herpesvirus 8 seroprevalence in patients with HIV-associated non-Hodgkin's lymphoma. J Acquir Immune Defic Syndr. 2001 Feb 1;26(2):182–184. doi: 10.1097/00042560-200102010-00013. [DOI] [PubMed] [Google Scholar]
  12. Hansen P. B., Penkowa M., Kirk O., Skinhøj P., Pedersen C., Lisse I., Kiss K., Zhou X., Hamilton-Dutoit S. J. Human immunodeficiency virus-associated malignant lymphoma in eastern Denmark diagnosed from 1990-1996: clinical features, histopathology, and association with Epstein-Barr virus and human herpesvirus-8. Eur J Haematol. 2000 Jun;64(6):368–375. doi: 10.1034/j.1600-0609.2000.90126.x. [DOI] [PubMed] [Google Scholar]
  13. Hayes R. B., Pottern L. M., Strickler H., Rabkin C., Pope V., Swanson G. M., Greenberg R. S., Schoenberg J. B., Liff J., Schwartz A. G. Sexual behaviour, STDs and risks for prostate cancer. Br J Cancer. 2000 Feb;82(3):718–725. doi: 10.1054/bjoc.1999.0986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Howard M. R., Whitby D., Bahadur G., Suggett F., Boshoff C., Tenant-Flowers M., Schulz T. F., Kirk S., Matthews S., Weller I. V. Detection of human herpesvirus 8 DNA in semen from HIV-infected individuals but not healthy semen donors. AIDS. 1997 Feb;11(2):F15–F19. doi: 10.1097/00002030-199702000-00001. [DOI] [PubMed] [Google Scholar]
  15. Iscovich J., Boffetta P., Brennan P. Classic Kaposi's sarcoma as a first primary neoplasm. Int J Cancer. 1999 Jan 18;80(2):173–177. doi: 10.1002/(sici)1097-0215(19990118)80:2<173::aid-ijc2>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  16. Martin J. N., Ganem D. E., Osmond D. H., Page-Shafer K. A., Macrae D., Kedes D. H. Sexual transmission and the natural history of human herpesvirus 8 infection. N Engl J Med. 1998 Apr 2;338(14):948–954. doi: 10.1056/NEJM199804023381403. [DOI] [PubMed] [Google Scholar]
  17. Melbye M., Cook P. M., Hjalgrim H., Begtrup K., Simpson G. R., Biggar R. J., Ebbesen P., Schulz T. F. Risk factors for Kaposi's-sarcoma-associated herpesvirus (KSHV/HHV-8) seropositivity in a cohort of homosexual men, 1981-1996. Int J Cancer. 1998 Aug 12;77(4):543–548. doi: 10.1002/(sici)1097-0215(19980812)77:4<543::aid-ijc12>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  18. Monini P., de Lellis 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 May 2;334(18):1168–1172. doi: 10.1056/NEJM199605023341805. [DOI] [PubMed] [Google Scholar]
  19. Moore P. S., Boshoff C., Weiss R. A., Chang Y. Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science. 1996 Dec 6;274(5293):1739–1744. doi: 10.1126/science.274.5293.1739. [DOI] [PubMed] [Google Scholar]
  20. Nador R. G., Cesarman E., Chadburn A., Dawson D. B., Ansari M. Q., Sald J., Knowles D. M. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood. 1996 Jul 15;88(2):645–656. [PubMed] [Google Scholar]
  21. Oksenhendler E., Duarte M., Soulier J., Cacoub P., Welker Y., Cadranel J., Cazals-Hatem D., Autran B., Clauvel J. P., Raphael M. Multicentric Castleman's disease in HIV infection: a clinical and pathological study of 20 patients. AIDS. 1996 Jan;10(1):61–67. [PubMed] [Google Scholar]
  22. Otsuki T., Kumar S., Ensoli B., Kingma D. W., Yano T., Stetler-Stevenson M., Jaffe E. S., Raffeld M. Detection of HHV-8/KSHV DNA sequences in AIDS-associated extranodal lymphoid malignancies. Leukemia. 1996 Aug;10(8):1358–1362. [PubMed] [Google Scholar]
  23. Pauk J., Huang M. L., Brodie S. J., Wald A., Koelle D. M., Schacker T., Celum C., Selke S., Corey L. Mucosal shedding of human herpesvirus 8 in men. N Engl J Med. 2000 Nov 9;343(19):1369–1377. doi: 10.1056/NEJM200011093431904. [DOI] [PubMed] [Google Scholar]
  24. Radkov S. A., Kellam P., Boshoff C. The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene Hras transforms primary rat cells. Nat Med. 2000 Oct;6(10):1121–1127. doi: 10.1038/80459. [DOI] [PubMed] [Google Scholar]
  25. Ridolfo A. L., Santambrogio S., Mainini F., Vago L., Gervasoni C., Gori A., Parravicini C., Monforte A., Galli M. High frequency of non-Hodgkin's lymphoma in patients with HIV-associated Kaposi's sarcoma. AIDS. 1996 Feb;10(2):181–185. doi: 10.1097/00002030-199602000-00008. [DOI] [PubMed] [Google Scholar]
  26. Shibata D., Weiss L. M., Hernandez A. M., Nathwani B. N., Bernstein L., Levine A. M. Epstein-Barr virus-associated non-Hodgkin's lymphoma in patients infected with the human immunodeficiency virus. Blood. 1993 Apr 15;81(8):2102–2109. [PubMed] [Google Scholar]
  27. Sitas F., Carrara H., Beral V., Newton R., Reeves G., Bull D., Jentsch U., Pacella-Norman R., Bourboulia D., Whitby D. Antibodies against human herpesvirus 8 in black South African patients with cancer. N Engl J Med. 1999 Jun 17;340(24):1863–1871. doi: 10.1056/NEJM199906173402403. [DOI] [PubMed] [Google Scholar]
  28. Soulier J., Grollet L., Oksenhendler E., Cacoub P., Cazals-Hatem D., Babinet P., d'Agay M. F., Clauvel J. P., Raphael M., Degos L. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood. 1995 Aug 15;86(4):1276–1280. [PubMed] [Google Scholar]
  29. Staskus K. A., Zhong W., Gebhard K., Herndier B., Wang H., Renne R., Beneke J., Pudney J., Anderson D. J., Ganem D. Kaposi's sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol. 1997 Jan;71(1):715–719. doi: 10.1128/jvi.71.1.715-719.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tarte K., Chang Y., Klein B. Kaposi's sarcoma-associated herpesvirus and multiple myeloma: lack of criteria for causality. Blood. 1999 May 15;93(10):3159–3164. [PubMed] [Google Scholar]

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