HIV and malignancy
latent EBV genes/proteins
-LMP1: induce lympohma, -LMP2: essential for survival of germinal cell -EBV nuclar angitgen 2: transforms cells -EBV encoded RNAs: target innate immune signalling by blokcing RNA dependent protein kinase which stops protein translation after viral infection
two stages of KS
-T0: limited KS, skin and or ln and /or minimal oral disease -T1: advance, systemic Ks, tumor associated edema or ulceration, extensive oral disease and/or viscera
why increased risk of cancer in HIV/AIDS
-ag driven stimulation leding to hypermutations of B cell s and thus b cell lymphomas -decreased immune surveillance -opportunistic oncogenic viruses: EBV, HHV8(aka KSHV), HPV
agressive subtypes of ATLL
-aggressive: high LDH, adenopathy, multi organ involvemnt acute leukemia phase and lymphomatous phase, bone lytic lesions -indolent chronic is non progressing leukemia, and smoldering skin involvement, often lung very poor outcome
burkitt lymphoma and EBV
-almost all in african variant -30% of aids related
pimary effusion lymphoma (PEL)
-body cavity of serous effusions (pleural effusions and/or malignant ascites) -100% have HHV8 and 80% coinfected with EBV -poor prognosis -B cells without b cell markers
-early post transplant lymphoproliferative disorders -extra nodal NK - Tcell lymphoma, nasal type
-hihgly assoicated with EBV -100% EBV
what do the following cause -HHV8 -EBV -HPV -HTLV1
-kaposi, multicentric castleman's disease, primary effusion lymphoma -B and T cell lymphoma, nasopharyngeal CA, gastric cancers -Cervical Ca, anal carcinoma, genital cancers, oropharyngeal -adult T cell leukemia-lymphoma
tx of burkitt and HIV
-modivied CODOX-M/IVAC
HIV + diffuse large B cell lymphoma -incidence -clinical presentation (types) -EBV
-most common type of lymphoma in HIV/AIDS -germinal B cell (GCB type), activated B cell (ABC) -30% of cases
treatment for KS -T0 -T1
-reversal of immunosuppression, local treatment(intralesional chemo, cryto, radiation, retinoids) -chemo (liposomal doxorubicin, laclitaxel, vinca alkaloids), biological agents (interferon, emergin antiangiogenic agents
tx of HIV DLBCL
-standard first line chemo (R-CHOP) bolus -infusional regimens: EPOCH or CDE ad Rituximab is probably superior for advanced stage
Drug interactions with antiretroviral therapy and chemo -AZT -Cyp3A4 inhibitors
-zidovudine should be avoided due to myelosupppressvie effects -avoid ritonavir voosted regimens due to increased chemo drug levels
AIDS associated primary CNS lymphoma
100% association with EBV prognosis was poor pre HAART but improving now Methotrexate based chemo with cART adminstered during HD-MTX
oncogenic subtypes of HPV
16,18
plasmablastic lymphoma (PBL)
80% assoicated with eBV in HIV usually tumor in the mouth B cells are usually CD20 negative MYC translocations common
HTLV1 associated conditions
ATLL (lymphocytosis and cutaneous lesions) AI conditions (HAM/tsp is super serious) opportunistic infections (PCP, strongyloides..scabies,)
poor prognostic features of HIV DLBCL
CD4 below 100 ABC subtype CNS involvement
HPV oncogenic proteins
E6 targets p53 E7 interacts with pRB
tx for AIDS - PEL
EPOCH is preferred investigational is tryiing to target viruses vorinostat-EPOCH vorinostat induces lytic reaction of virus within cell
non aids defining cancers for which HIV patients are at an increased risk
anal, hodgkin, liver these did not decrease when antiretroviral therapy was introduced
HPV and HIV
at increased risk for HPV infection HIV positive women have 10x incidnec of cervical cancer
HPV cancers and estimated HPV asssociation
cervix 100% anus 85% vagina 40 penis 40 oral pharyngeal 40
HHV8 is much rarer than EBV, where is HHV 8 high
homosexuals and in central africa
AIDS defining cancers
kaposi sarcoma, non hodgkin lymphoma, cervical cancer these decreased when antiretroviral cancer was introduced
most common hodgkin lymphoma subtype in hiv positive
mixed cellularity remember CD30 (bretuximab target) and CD15 positive RS cells
Kaposi's sarcoma -common -immune compromised -classic KS
most common AIDS defining malignancy -HIV/AIDS, post transplant, immunosuppressive drugs -mediterranean and european jewish pops
hodgking lymphoma and EBV
only 50% association with EBV in general population -but among AIDS related it is close to 100%
HTLV1 asoicated Adult T cell leukemia lymphoma
retrovirus known to cause human cancer also targets CD4+ T cells clover leaf cell!
rituximab and HIV NHL
should be used with care because already immunosuppresed and may put at increased risk for infection due to it attacking B cells
HIV /hodgkin lymphoma tx
standard ABVD and cART pretty good prognosis current trial: AVD (no bleomycin) and brentuximab (antiCD30 and drug conjugate)
viral encodd genes/oncogenes in HHV8
vIL6, vBcl2, vFLIP, VGPCR K-1 (activates survival factors) LANA: inhibits p53 and Rb -vIRF1 and vIRF3: inhibit interferon signaling
tx of HPV and HIV
vaccination yearly pap smears