1 / 35

Cancers in HIV: A Growing Problem

Cancers in HIV: A Growing Problem. Ronald Mitsuyasu, MD Professor of Medicine Director, UCLA Center for Clinical AIDS Research and Education Group Chairman, AIDS Malignancy Consortium (AMC). AIDS Defining Cancers. Kaposi’s sarcoma B-cell non-Hodgkin’s lymphoma Primary CNS lymphoma

reuben
Download Presentation

Cancers in HIV: A Growing Problem

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Cancers in HIV:A Growing Problem Ronald Mitsuyasu, MD Professor of Medicine Director, UCLA Center for Clinical AIDS Research and Education Group Chairman, AIDS Malignancy Consortium (AMC)

  2. AIDS Defining Cancers • Kaposi’s sarcoma • B-cell non-Hodgkin’s lymphoma • Primary CNS lymphoma • Cervical cancer

  3. Number of people living with AIDS, AIDS-defining cancers, non-AIDS-defining cancers, and all cancers in the USA during 1991–2005. Cancer Incidences in HIV in USA Shiels M S et al. J Natl Cancer Inst 2011;103:753-762

  4. Categorizing Cancers in PWHA AIDS Defining Cancer (decreasing) KS NHL (BL, CNS, DLCBL) Cervical Cancer ( added in 1993) Non AIDS defining Cancers (increasing) Anal Cancer Lung Cancer Hodgkin Lymphoma Liver Cancer Elevated risk but rare Merkel Carcinoma Leiomyosarcoma Salivary gland LEC Unchanged risk Breast Colorectal Prostate Follicular lymphoma

  5. Breakdown of causes of death: France 2005 AIDS Cancer Hepatitis C CVD Suicide Non-AIDS infection Accident Hepatitis B Liver disease OD / drug abuse neurologic renal pulmonary digestive iatrogenic metabolic psychiatric other unknown N = 937 deaths ANRS EN19 Mortalité 2005 Lewden JAIDS 2008, 48:590-9 Percent

  6. Cancers in HIV Disease AIDS-DefiningVirus • Kaposi’s Sarcoma HHV-8 • Non-Hodgkin’s Lymphoma EBV, HHV-8 (systemic and CNS) • Invasive Cervical Carcinoma HPV Non-AIDS Defining • Anal Cancer HPV • Hodgkin’s Disease EBV • Leiomyosarcoma (pediatric) EBV • Squamous Carcinoma (oral) HPV • Merkel cell Carcinoma MCV • Hepatoma HBV, HCV

  7. HIV-Cancers: Overview • Non-AIDS defining malignancies • Anogenital neoplasia • Lymphomas • Kaposi’s Sarcoma • Cancer Prevention

  8. Non-AIDS Defining CancersNADC

  9. Non AIDS-defining CancersEmerging Epidemiologic Features Engels EA, Int J Cancer. 2008;123:187-194

  10. Factors Contributing to the Increasein Cancer cases in HIV 4-fold increase in HIV/AIDS Population Patients living longer and not dyeing of OI Rising proportion of HIV pts > 50 yo Cancer incidence increases with age Greater and earlier start to smoking in HIV Increase in some CA incidence rate among HIV Lung (3X), anal (29X), liver (3X), HL (11X) Suggests may be additional risk from HIV

  11. Anogenital Cancers

  12. Anogenital Cancers • Invasive cervical carcinoma • Considered an AIDS-defining condition • Leading cause of cancer death in women worldwide • Anal cancer1 • Not AIDS defining but very common and growing incidence • Oral and Head/Neck cancer also HPV related • HPV involvement1-2 • Both derive from precancerous lesions due to HPV • Most cancer causing strains: 16, 18, 31, 33, 35, 45 • Repeated infections and infection with multiple HPV strains increase the risk of developing neoplasia • Cancer can be prevented with early diagnosis and vaccines 1Phelps RM, et al. Int J Cancer. 2001;94:753-757. 2Martin F, et al. Sex Transm Infect. 2001;77:327-331.

  13. Spectrum of HPV disease Low-grade disease High-grade disease Morphologic Continuum

  14. Anal anatomy Rectalmucosa Columns ofMorgagni Levator animuscle Dentate(pectinate)line Deep Externalsphincter animuscles Skin Squamousmucosa Subcutaneous Superficial Ryan DP et al. New Engl J Med. 2000;342:792-800.

  15. Anal and Cervical Cancer Incidence Cervical cancer prior to cervical cytology screening in general pop: 40-50/100,000 Cervical cancer currently: 8-10/100,000 Anal cancer among HIV+ MSM in USA: up to 137/100,000 American Cancer Society. Cervical cancer facts. 2006.Daling JR et al. N Engl J Med. 1987;317:973-977. Chin-Hong PU, Palefsky JM. Dermatol Ther. 2005;18:67-76.

  16. Prevalence of anal HPV detection among MSMPopulation-based data Prevalence, % All participants HIV-negativeparticipants HIV-seropositiveparticipants Chin-Hong et al. Ann Int Med. 2008;149;300-6. 16

  17. Lymphomas

  18. Pathology of AIDS-RelatedNon-Hodgkin’s Lymphoma • Small noncleaved-cell lymphoma • Burkitt’s lymphoma and Burkitt-like lymphoma • Immunoblastic lymphoma (primary CNS) • Diffuse large-cell lymphoma (90% CD20+) • Large noncleaved-cell lymphoma • CD30+ anaplastic large B-cell lymphoma • Plasmablastic lymphoma • Advanced stage (>75% III or IV) • Extranodal involvement • Central nervous system, liver, bone marrow, gastrointestinal Tirelli U, et al. AIDS. 2000;14:1675-1688.

  19. EBV-positive tumors Burkitt’s lymphoma Nasopharyngeal carcinoma

  20. AIDS-related Lymphoma Experience Suggests Cancer Treatment Outcome Can be Equivalent to General Population Besson et al. Blood. 2001; 98: 2339-2344 Little et al Blood. 2003; 101: 4653-4659

  21. Hodgkin’s Disease • Association with HIV-infection • Hodgkin’s disease: RR: 5 to 30 • Non-Hodgkin’s disease: RR: 24 to 165 • Incidence increasing rapidly in post HAART era • >95% are EBV+ • Patients with HIV present with: • B symptoms (70% to 96%), worse histology, higher-stage tumor (74% to 92% are III or IV), bone marrow involvement (40% to 50%), pancytopenia • Good response to MOPP/ABV • Complete response: 74.5% • 2-year disease-free survival: 62% but more relapses in HIV • Early good results with Stanford V, BEACOPP and brentuximab vendotin Gerard L, et al. AIDS. 2003;17:81-87.

  22. Kaposi’s Sarcoma

  23. Kaposi’s Sarcoma • One of the first recognized AIDS-defining illnesses • Vascular tumor that may involve mucocutaneous, lymphatic, gastrointestinal, and pulmonary sites • Human herpesvirus-8 (HHV8) or KSHV • HHV8 • DNA virus found in both HIV+ and HIV- KS. • Tropism for B cells and endothelial cells, high titers in saliva • Also associated with primary effusion lymphoma, Castleman’s disease, and angioimmunoblastic lymphadenopathy in HIV • Genome codes for viral homologs of human proteins involved in cell cycle regulation and signaling • HIV- and Kaposi’s sarcoma-induced angiogenic and inflammatory cytokines also stimulate Kaposi’s sarcoma cell growth

  24. AIDS-associated Kaposi’s Sarcoma • Transmission • Mostly MSM in US • IVDU and Heterosexual as well • Resource limited setting – Africa and S. America • KS still most common cancer in HIV • Prevalence • 1300 cases/100,000 persons/yr 1992 • 170 cases/100,000 persons/yr 2006 • Decline of 10% / year • Cause of considerable morbidity and mortality in Africa and Latin America

  25. Clinical Manifestations • Mucocutaneous, macular or nodular, dark color • Lymphadenopathy • Visceral • Often asymptomatic • Mouth, esophagus, stomach, bowel, liver, spleen • Pulmonary KS • Rapidly fatal • Dyspnea without fever, hemoptysis • Diffuse reticulo-nodular infiltrates, mediastinal enlargement, pleural effusions • Edema, can be extensive and symptomatic

  26. Kaposi’s Sarcoma

  27. Oral Kaposi’s Sarcoma

  28. KS in Africa – A “Different” Disease?

  29. Pulmonary KS on CXR & CT Scan

  30. Radiation therapy Photodynamic (laser) therapy Cryotherapy Alitretinoin gel – 9-cis retinoic acid (topical) Antiretroviral therapy Liposomal anthracyclines Paclitaxel Bleomycin Vinca alkaloids Gemcitabine Alpha Interferon Treatments for Kaposi’s Sarcoma Local1 Systemic1,2 1Levine AM, et al. Eur J Cancer. 2001;37:1288-1295. 2Mitsuyasu RT, et al. Cancer Management. 2008:609-632.

  31. Cancer Prevention • Smoking Cessation – Highest priority • Hepatitis and HPV vaccination • Yearly cervical and anal Pap tests – Gyn and HRA • Maintain high index of suspicion for cancer • Yearly breast, prostate (incl. PSA) exam • Advise sun screen and avoid overexposure • Complete family history for malignancies • If Hepatitis B or C positive, follow LFTs and perhaps AFP periodically (?)

  32. Summary • As patients live longer with HIV, morbidity and mortality from cancers are increasing • The types of cancers in HIV may vary in different populations around the world • Treatment of malignancies in HIV should be vigorous and appropriate to the situation • Side effects of therapy should be treated/prevented • Prevention strategies for virally-associated malignancies in HIV need to be investigated • Through prospective clinical trials research can treatment and prevention strategies be effectively evaluated

More Related