HIV and cancer in referral hospitals from four West African countries The IeDEA West Africa Collaboration A Jaquet, M Odutola, DK Ekouevi, A Tanon, E Oga, J Akakpo, M Charurat, DM Zannou, SP Eholie, AJ Sasco, E Bissagnene, C Adebamowo, F Dabis 20th International AIDS Conference, Melbourne, Australia, 23 July 2014

Context In sub-Saharan Africa, mortality and morbidity of HIV- infected people are mainly mediated by opportunistic infections, however: – With ART scale-up, cancer will soon substantially contribute to disease burden of Africans with HIV as already observed in high- resource countries – Etiologic factors interacting with HIV infection and leading to the occurrence of cancers are quite different Need to provide an overview of the intersection between the cancer and the HIV epidemics in sub-Saharan Africa 2

Objective Estimate the association between HIV infection and selected types of cancers among patients hospitalized for a malignant condition in four West African countries 3

Methods (1) Study design & population (1) A case-referent study was initiated in referral hospitals of Côte d’Ivoire (Abidjan) and Benin (Cotonou) and subsequently extended to Togo (Lome) and Nigeria (Abuja, Benin City) 4

Methods (2) Study design & population During a 12-month period, each participating clinical ward selected all adult patients seeking care with a confirmed diagnosis of cancer – Histological examination systematically proposed (supported by the project) – Included patients interviewed to collect socio-demographic (age, gender, place of living..) & behavioural data (sexual & reproductive life) – Systematic HIV testing: Determine® + confirmation (Genie 2®) 5

Methods (3) Analysis HIV prevalence reported for selected types of cancer – AIDS-defining (Kaposi Sarcoma, Non Hodgkin lymphoma & Invasive cervical cancer) – A subset of non-AIDS defining cancers (known or suspected to be linked with HIV infection from previous reports) Compared to a referent group of cancers not reported in the literature to be associated with HIV – Colorectal, Oesophagus, Gastric, Breast, Ovary, Endometrium, Prostate, Kidney, Bladder & urinary ducts, Endocrine tumours Odds ratio (OR) [95% CI] estimated for these selected cancers using an unconditional logistic model 6

Results (1) 7 HIV + (n=184)HIV – (n=1,460)PTotal (N=1,644) Age, median [IQR]41.5 [35 – 48]50 [38 – 61]< [38 – 60] Womenn (%)127 (69.0) 864 (59.2) (60.3) Countryn (%) Benin Côte d’Ivoire Nigeria Togo 184 (100.0) 12 (6.5) 116 (63.0) 46 (25.0) 10 (5.5) 1,460 (100.0) 79 (5.4) 809 (55.4) 513 (35.1) 59 (4.1) ,644 (100.0) 91 (5.5) 925 (56.3) 559 (34.0) 69 (4.2) Sexual partners* n (%) 0 to 2 2 to 4 5 and over 87 (49.4) 49 (27.8) 40 (22.7) 824 (58.5) 393 (27.9) 191 (13.6) < (57.5) 442 (27.9) 231 (14.6) Characteristics of included adult patients according to HIV status Lifetime number of sexual partners declared (21 missing values)

Results (2) 8 Most reported cancer types according to HIV status in participating referral hospitals (Benin, Côte d’Ivoire, Nigeria and Togo) * Non Hodgkin Lymphoma † Oral cavity, larynx, pharynx (%)

Results (3) 9 Cancer site or morphological type* HIV infectionMultivariate† Comparison group n/N (%)OR95% CIP Total Women (for cervical cancer) 35/792 (4.4) 21/483 (4.3) 1.0 AIDS classifying cancers Kaposi sarcoma (M9140)37/58 (63.8) – 63.0< Non Hodgkin lymphoma (M9591, ) 22/133 (16.5) – 6.9< Cervical cancer (C53)47/258 (18.2) – 8.4< Association between AIDS defining cancers and HIV infection in participating referral hospitals (Benin, Côte d’Ivoire, Nigeria and Togo) † Adjusted on age, sex and lifetime number of sexual partners * According to International Classification of Diseases for Oncology, 3rd Edition

Results (4) 10 Cancer site or morphological type*HIV infection Multivariate† Comparison group n/N (%)OR95% CIP Total Women (for cervical cancer) 35/792 (4.4) 21/483 (4.3) 1.0 Non AIDS classifying cancers Anal, Vulvar, Vaginal (C21, C51, C52)10/25 (40.0) – 45.2< Squamous cell skin cancers (C44, M ) 6/29 (20.1) – 15.2< Primary liver cancers (C22)7/69 (10.1) – Hodgkin lymphoma (M )3/23 (13.0) – Association between non AIDS defining cancers and HIV infection in participating referral hospitals (Benin, Côte d’Ivoire, Nigeria and Togo) † Adjusted on age, sex and lifetime number of sexual partners * According to International Classification of Diseases for Oncology, 3rd Edition

Discussion (1) AIDS-defining cancers are strongly associated with HIV infection and are leading causes of cancer in West Africa A significant association is now reported between HIV infection and some Non-AIDS defining cancers including cancers of the ano-genital organs and squamous cell skin cancer Concordant with previous findings from South Africa based on the same methodological approach (Stein et al, Int J Cancer 2008) – Ano-genital cancers: OR=2.2 (95% CI 1.4–3.3) – Squamous cell skin cancer: OR=2.6 (95% CI 1.4–4.9) 11

Discussion (2) Association between HIV and primary liver cancer Concordant with results reported from linkage studies in high-resource settings Limitations - Sample size - No standardized case definition of hepatocarcinoma - Risk factors such as chronic viral hepatitis not recorded Need to conduct dedicated case-control studies Ongoing project: “HIV and hepatocarcinoma in Benin, Côte d’Ivoire, Mali & Togo” 12

Conclusions The study provided a rather representative and precise picture of the association between AIDS-defining cancers and HIV infection in West Africa HPV-related cancers including cervical cancer but also ano- genital cancer and squamous cell skin cancer are reported here as leading causes of malignancies in people living with HIV As these cancers are amenable to prevention strategies, screening of HPV-related cancers among persons living with HIV is of paramount importance in West Africa 13

Acknowledgments All patients & medical staff that participated to the cancer studies HIV & Cancer studies coordinators & investigators Bordeaux: E Balestre, A Sasco Benin: J Akakpo, J Sehonou, DM Zannou Côte d’Ivoire: A Tanon, A. Attia, SP Eholie Nigeria: E Oga, M Odutola, E Jedy-Agba, M Charurat, C Adebamowo Togo: DK Ekouevi, B Goilibe PACCI regional center for data management : T.A. Azani, P Coffie & colleagues IeDEA WA PIs: E Bissagnene, F Dabis Funding The National Cancer Institute (NCI), the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) and the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. National Institutes of Health (NIH), as part of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) under Award Number U01AI