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Cancers in HIV: A Growing Problem PowerPoint Presentation

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Description : Check out this medical presentation on anal cancer, which is titled "Cancers in HIV: A Growing Problem", to know about AIDS defining cancers including kaposi’s sarcoma, b-cell non-Hodgkin’s lymphoma, primary CNS lymphoma, and cervical cancer.

Tags : anal cancer, Cancers, HIV, kaposi’s sarcoma, b-cell non-Hodgkin’s lymphoma, primary CNS lymphoma, cervical cancer, Liver cancer, Lung cancer

Published on : May 06, 2021 | Views : 1270 | Downloads : 1

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Slide 1-

Ronald Mitsuyasu, MD Professor of Medicine Director, UCLA Center for Clinical AIDS Research and Education Group Chairman, AIDS Malignancy Consortium (AMC) Cancers in HIV:A Growing Problem
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AIDS Defining Cancers Kaposi’s sarcoma B-cell non-Hodgkin’s lymphoma Primary CNS lymphoma Cervical cancer
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Number of people living with AIDS, AIDS-defining cancers, non-AIDS-defining cancers, and all cancers in the USA during 1991–2005. Shiels M S et al. J Natl Cancer Inst 2011;103:753-762 Cancer Incidences in HIV in USA
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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
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Cancer is the One of the Most Frequent Causes of Death in HIV-Infected Patients Mortalité 2000 and 2005 studies: Bonnet et al., Cancer 101; 317:2004 and CID 48;633: 2009.
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7 Notable Cancers in HIV Refs: Engels AIDS 2006, Biggar JNCI 2007, Engels Int J Cancer 2008, Chaturvedi JNCI 2009, Guiguet Lancet Oncol 2009
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Cancers in HIV Disease AIDS-Defining Virus 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
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HIV-Cancers: Overview Non-AIDS defining malignancies Anogenital neoplasia Lymphomas Kaposi’s Sarcoma Cancer Prevention
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Non-AIDS Defining CancersNADC
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Non AIDS-defining CancersEmerging Epidemiologic Features Engels EA, Int J Cancer. 2008;123:187-194
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Factors Contributing to the Increasein Cancer cases in HIV 4-fold increase in HIV/AIDS Population Patients living longer and not dying 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 (13X) Suggests may be additional risk from HIV
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Pathogenesis of Cancer in HIV Many are virally-induced cancers, but not all Immune activation, immune dysregulation, inflammation and decreased immune surveillance HIV may activate cellular genes or proto-oncogenes or inhibit tumor suppressor genes HIV induces genetic instability (e.g 6 fold higher number of MA in HIV lung CA over non-HIV)1 Increase susceptibility to effects of carcinogens Endothelial/epithelial cell abnormalities induced or facilitated by HIV may allow for cancer development Population differences based on genetics and exposure to carcinogens Wistuba Il, Pathogenesis of NADC: a review. AIDS Pt Care 1999;13:415-26
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Outcomes of cancer in HIV With prolonged survival of HIV population and aging, more people will develop cancer, especially NADCs. HIV-infected cancer patients may have worse outcomes in some cancers Late presentation, advanced stage Poor access to care Medical comorbidity, treatment toxicity Unclear if HIV has adverse impact on cancer behavior, immune control, cancer-free survival Limited data for guiding cancer treatment in HIV-infected people Biggar JAIDS 2005, Little J Clin Oncol 2008, Rengan Lancet Oncol 2012, Suneja AIDS 2013
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Anogenital Cancers
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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.
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Spectrum of HPV disease Morphologic Continuum Low-grade disease High-grade disease
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Anal anatomy Ryan DP et al. New Engl J Med. 2000;342:792-800.
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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.
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19 Prevalence of anal HPV detection among MSMPopulation-based data Chin-Hong et al. Ann Int Med. 2008;149;300-6. Prevalence, % HIV-seropositiveparticipants HIV-negativeparticipants All participants
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Redfield IRC 2100
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Lymphomas
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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.
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EBV-positive tumors Burkitt’s lymphoma Nasopharyngeal carcinoma
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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
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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.
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Kaposi’s Sarcoma
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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
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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
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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
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Kaposi’s Sarcoma
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Oral Kaposi’s Sarcoma
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KS in Africa – A “Different” Disease?
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Pulmonary KS on CXR & CT Scan
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Treatments for Kaposi’s Sarcoma Radiation therapy Photodynamic (laser) therapy Cryotherapy Alitretinoin gel – 9-cis retinoic acid (topical) Antiretroviral therapy Liposomal anthracyclines Paclitaxel Bleomycin Vinca alkaloids Gemcitabine Alpha Interferon Local1 Systemic1,2 1Levine AM, et al. Eur J Cancer. 2001;37:1288-1295. 2Mitsuyasu RT, et al. Cancer Management. 2008:609-632.
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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 (?)
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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
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Thank You For information on AMC clinical trials see:http://www.aidscancer.org For information on NCI programs in HIV cancer see: http://www.cancer.gov/cancertopics/types/AIDS To refer for AMC clinical trials in LA, call UCLA CARE Center 310-557-1891 ask for Maricela Gonzalez or page/email Dr. Mitsuyasu, rmitsuya@mednet.ucla.edu