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