Nice Marseille Montpellier Nantes Paris Tourcoing Clermont Ferrand Lyon St Etienne Besançon Reims Toulouse Strasbourg Guadeloupe Martinique 0289 - AIDS- AND NON–AIDS-DEFINING CANCER INCIDENCE BETWEEN 2010-2015 IN THE DAT’AIDS COHORT Camelia Protopopescu 1 PhD, Antoine Chéret 2 MD PhD, Alain Makinson 3 MD, David Rey 4 MD, Claudine Duvivier 5 MD, Clotilde Allavena 6 MD, Pascal Pugliese 7 MD, Tristan Ferry 8 MD, Thomas Huleux 9 MD, Pierre Delobel 10 MD, André Cabié 11 MD, Isabelle Lamaury 12 MD, Patrizia Carrieri 1 PhD, Isabelle Poizot - Martin 13 MD, for the Dat’AIDS study group Seattle, Washington March 4–7, 2019 1. Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Marseille 2. Université Paris Descartes, Sorbonne Paris Cité, EA7327, Paris, Department of Internal Medicine, Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre 3.Department of infectious diseases, Montpellier University Hospital, INSERM U1175/IRD UMI 233, Montpellier 4. Le Trait d'Union, HIV Infection Care Centre, Hôpitaux Universitaires, Strasbourg 5. AP-HP-Necker Hospital, Infectious Diseases Department, Necker-Pasteur Infectiology Center, Paris; Medical Center of Institut Pasteur, Necker- Pasteur Infectiology Center, Paris; Paris Descartes University, Sorbonne Paris Cité, EA7327, Paris; IHU Imagine, Paris 6. Infectious Diseases Department, CHU Hôtel-Dieu, Nantes 7. Université Côte d’Azur, CHU de Nice, Nice 8. Service de Maladies Infectieuses, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Villeurbanne 9. Service Universitaire des Maladies Infectieuses et du Voyageur - Centre Hospitalier G. DRON Tourcoing 10. CHU de Toulouse, Service des Maladies Infectieuses et Tropicales-INSERM, UMR1043- Université Toulouse III Paul Sabatier, Toulouse, France 11. CHU de Martinique, Fort-de-France, Université des Antilles, EA4537, Fort-de-France, Inserm CIC1424, CHU de Martinique, Fort-de-France 12. CHU de Guadeloupe, Pointe-à-Pitre 13. Aix-Marseille Univ, INSERM, IRD, SESSTIM, APHM Sainte-Marguerite, Clinical Immuno-Hematological Unit Marseille France. Although antiretroviral therapy has reduced the risk of developing AIDS- defining cancers, people living with HIV (PLWH) still have a high risk for some cancers, in particular virus-related (1,2). Given the increased life expectancy of PLWH, incidence of age- and behavioral-related cancers are expected to increase. However, data concerning recent incidence trends are scarce. BACKGROUND OBJECTIVES • To assess AIDS- and Non-AIDS-defining cancer incidence in PLWH in France between 2010 and 2015. • To assess the evolution of breast, colorectal, prostate, anal, liver, bronchopulmonary, Hodgkin lymphoma (HL), head and neck cancer incidence. For incidence assessment, prevalent cases, occurring within 30 days after enrollment in the cohort, were excluded. If more than one cancer occurred in the same patient during the study period, only the first case was considered. Standardized incidence ratios relatively to the French general population were calculated using the method of indirect standardization (3, 4). Statistical analyses were performed with STATA and SAS. Dat’AIDS Study Group: C. Drobacheff-Thiébaut, A. Foltzer, K. Bouiller, L. Hustache- Mathieu, C. Chirouze, Q. Lepiller, F. Bozon, O Babre, A.S. Brunel, P. Muret (Besançon ) ; H. Laurichesse, O. Lesens, M. Vidal, N. Mrozek, C. Aumeran, O. Baud, V. Corbin, P. Letertre-Gibert, S. Casanova, J. Prouteau, C. Jacomet (Ferrand) ; I. Lamaury, I. Fabre, E. Curlier, R. Ouissa, C. Herrmann-Storck, ,B. Tressieres, T. Bonijoly,M.C. Receveur, F. Boulard, C.Daniel, C.Clavel (Guadeloupe ) ; D. Merrien, P. Perré, T. Guimard, O. Bollangier, S. Leautez, M. Morrier, L. Laine (Roche sur Yon) ; F. Ader, A. Becker, F. Biron, A. Boibieux, L. Cotte, T. Ferry, P Miailhes, T. Perpoint, S. Roux, C. Triffault-Fillit, S. Degroodt, C. Brochier, F Valour, C. Chidiac (Lyon) ; A. Ménard, A.Y. Belkhir, P.Colson, C. Dhiver, A.Madrid, M.Martin-Degiovani, L. Meddeb, M. Mokhtari, A.Motte, A.Raoux, I. Ravaux, C.Tamalet, C. Toméi, H. Tissot Dupont (IHU Méditerranée) ; S. Brégigeon, O. Zaegel-Faucher, V. Obry-Roguet, H Laroche, M. Orticoni, M.J. Soavi, P Geneau de Lamarlière, E Ressiot, M.J. Ducassou, I. Jaquet, S. Galie, A Galinier, P. Martinet, M. Landon, A.S. Ritleng, A. Ivanova, C. Debreux, C. Lions, I. Poizot-Martin (Marseille Ste Marguerite) ; S. Abel, O. Cabras, L. Cuzin, K. Guitteaud, M. Illiaquer, S. Pierre-François, L. Osei, J. Pasquier, K. Rome, E. Sidani, JM Turmel, C. Varache, A. Cabié() ; N. Atoui, M. Bistoquet, E Delaporte, V. Le Moing, A. Makinson, N. Meftah, C. Merle de Boever, B. Montes, A. Montoya Ferrer, E. Tuaillon, J. Reynes (Montpellier ) ; M. André, L. Boyer, MP. Bouillon, M. Delestan, C. Rabaud, T. May, B. Hoen (Nancy) ; C. Allavena, C. Bernaud, E. Billaud, C. Biron, B. Bonnet, S. Bouchez, D. Boutoille, C. Brunet-Cartier, C. Deschanvres, N. Hall, T. Jovelin, P. Morineau, V. Reliquet, S. Sécher, M. Cavellec, A. Soria, V. Ferré, E. André-Garnier, A. Rodallec, M. Lefebvre, O. Grossi, O. Aubry, F. Raffi () ; P. Pugliese, S. Breaud, C. Ceppi, D. Chirio, E. Cua, P. Dellamonica, E. Demonchy, A. De Monte, J. Durant, C. Etienne, S. Ferrando, R. Garraffo, C. Michelangeli, V. Mondain, A. Naqvi, N. Oran, I. Perbost, S. Pillet, C. Pradier, B. Prouvost- Keller, K. Risso, V. Rio, PM. Roger, E. Rosenthal, S. Sausse I. Touitou, S. Wehrlen-Pugliese, G. Zouzou (Nice) ; L. Hocqueloux, T. Prazuck, C. Gubavu, A. Sève, A. Maka, C. Boulard, G. Thomas (Orleans ) ; A. Cheret, C.Goujard, Y.Quertainmont, E.Teicher, N. Lerolle, O.Deradji, A.Barrail-Tran (Paris Hop. Bicètre) ; R. Landman, V. Joly, J Ghosn, C. Rioux, S. Lariven, A. Gervais, F.X. Lescure, S. Matheron, F. Louni, , Z. Julia, C. Mackoumbou-Nkouka, S Le Gac C. Charpentier, D. Descamps, G. Peytavin, Y. Yazdanpanah (Hop. Bichat) ; K. Amazzough, G. Benabdelmoumen, P. Bossi, G. Cessot, C. Charlier, P.H. Consigny, F. Danion, A. Dureault, C. Duvivier, J. Goesch, R. Guery, B. Henry, K. Jidar, F. Lanternier, P. Loubet, O. Lortholary, C. Louisin, J. Lourenco, P. Parize, B. Pilmis, F Touam. (Hop. Necker Pasteur) ; M.A. Valantin, R. Tubiana, R Agher, S.Seang, L.Schneider, R.PaLich, C. Blanc, C. Katlama (Paris Hop. Pitié Salpétrière) ; J.L. Berger, Y. N’Guyen, D. Lambert, I. Kmiec, M. Hentzien, A. Brunet, V. Brodard, F. Bani-Sadr (Reims ) P. Tattevin, M. Revest, F. Souala, M. Baldeyrou, S. Patrat-Delon, J.M. Chapplain, F. Benezit, M. Dupont, M. Poinot, A. Maillard, C. Pronier, F. Lemaitre, C. Guennoun, M. Poisson-Vanier, T. Jovelin, J.P. Sinteff, C. Arvieux () ; E. Botelho-Nevers, A. Gagneux-Brunon, A. Frésard, V. Ronat, F. Lucht (Etienne) ; P. Fischer, M. Partisani, C Cheneau, M Priester, ML Batard, C Bernard-Henry, E de Mautort, S. Fafi- Kremer, D. Rey ( Strasbourg) ; M. Alvarez , N. Biezunski, A. Debard, C. Delpierre, P. Lansalot, L. Lelièvre, G. Martin-Blondel, M. Piffaut, L. Porte, K. Saune, P. Delobel (Toulouse ) ; F. Ajana, E. Aïssi, I. Alcaraz, V. Baclet, L. Bocket, A. Boucher, P. Choisy, T. Huleux, B. Lafon-Desmurs, A. Meybeck, M. Pradier, O. Robineau, N. Viget, M. Valette () Table 1- Patients’ characteristics • Most of patients with incident cancer cases were male and MSM. • They were significantly older, followed for HIV infection for a longer period of time and presented a higher number of previous cancer. • Nadir CD4, median CD4, CD8 count and CD4:CD8 ratio were significantly lower. RESULTS The incidence of Non-AIDS defining cancers remained relatively stable over the 2010-2015 period, overall and for both sexes, whereas AIDS-defining cancer incidence decreased significantly in men and overall. Distribution of cancer cases differed by sex, with AIDS-defining cancers as the most frequent cancers in men and breast cancer in women. With respect to the general population (3,4), no significant difference was observed for colorectal/anal cancer incidence,a significantly higher incidence was detected for liver cancer, Hodgkin lymphoma (overall and in both sexes) and head and neck cancer in women, while a significantly lower incidence was detected for breast, prostate and bronchopulmonary cancers (in men and overall), as recently reported for lung cancer (5). Further analyses are needed to better explore the role that specific risk behaviors such as tobacco and hazardous alcohol use may play on cancer incidence and interact with inflammation. Cancer incidence rate 2010- 2015 1. E. L. Yanik et al. J Clin Oncol 2016 34:3276- 3285 2. Yarchoan R et al N Engl J Med 2018; 378:1029–1041 3. Estimation nationale de l’incidence des cancers en France entre 1980 et 2012. Étude à partir des registres des cancers du réseau Francim Partie 2 – Hémopathies malignes METHODS Retrospective study using longitudinal data from 17 French HIV clinical centers contributing to the DAT'AIDS cohort (NCT 02898987ClinicalTrials.gov). AIDS and Non-AIDS defining cancer cases diagnosed between 01/2010 and 12/2015 were identified using ICD-10 codes. CONCLUSION 1 2 3 5 6 9 10 10 12 14 16 20 20 21 30 50 0 10 20 30 40 50 60 Oes ophagus Di g e sti ve Ca n ce r Pl e ura l /pe ri c ard i u m Me lanoma Genita l organs Meningealmali gnancy Sp i na l co rd /cra n i a l ner ves Ca n ce r l o ca ti on not accurate Lympho id l eukemia Sto ma c h Bone/carti lage Sa rc om a /co n ne c ti ve t is su Ov a ri an Bl a dd e r s ec ondary l y mp h n od e s Mu ltip le myel oma Ute ru s c o rpu s Kidney wit hout pelvis Ey e a n d oc u l ar annex es Uterus, locati on non accurat e Pa n cre a s Vu l va Thyroid gland Ho d g ki n lymphoma Co l o -Re cta l Kapos i Anal C anal He a d a n d Ne ck s ec ondary mali g n a nt tu mo r… Ce rv i cis uteri He p a t oc arcinom a Sk i n non mel anoma s ec ondary mali g n a nt tu mo r o the rs Bro n ch o p u l m on a ry Non Hodgk in lym phom a Bre a st Females: n= 299 cancer cases Distribution of first incident cancer case 2010-2015 0 20 0 40 0 60 0 80 0 2010 2011 2012 2013 2014 2015 Fem a le s Males Global p=0.04 p=0.03 p=0.13 AIDS-defining cancer 191.4/ 10 5 Person-Years (PY) [95% CI: 172.3-212.7] Non AIDS-defining cancer 0 20 0 40 0 60 0 80 0 2010 2011 2012 2013 2014 2015 Fem a le s Males Global p=0.48 p=0.85 p=0.17 548.8/ 10 5 Person-Years (PY) [95% CI: 515.6-584.1] Non AIDS-defining cancer incidence rate by year and by sex between 01/2010-12/2015 and Standardized Incidence Ratio (SIR) , Males: 232.9/ 10 5 PY [95% CI: 207.6-261.4] Females: 99.7/ 10 5 PY [95% CI: 76.8-129.6] Males: 601.3/ 10 5 PY [95% CI: 559.7-646.0] Females: 432.8 / 10 5 PY [95% CI: 381.6-490.7] 2 4 10 14 16 21 23 28 41 52 69 73 76 76 111 125 194 0 50 10 0 15 0 20 0 25 0 Ga l d b ladder Cholangioc arcinom a Uri n a ry g e n ital organ Ey e a n d oc u l ar annex es Oth e r e nd o cri n e g lands Ca n ce r l o ca ti on not accurate Sa rc om a /co n ne c ti ve t is su Genita l organs Adrenal gl and Lympho id l eukemia Di g e sti ve Ca n ce r Pl e ura l /pe ri c ard i u m Bone/carti lage Peni s Others leukemi a not accurate Bre a st Thyroid gland Oes ophagus Sto ma c h Te sti cl e Brain Myelo id l eukemia Me lanoma s ec ondary mali g n a nt tu mo r l u ng /d i gest ive Mu ltip le myel oma s ec ondary l y mp h n od e s Pa n cre a s s ec ondary mali g n a nt tu mo r o the rs Bl a dd e r Kidney wit hout pelvis Co l o -Re cta l Anal C anal He a d a n d Ne ck Bro n ch o p u l m on a ry Ho d g ki n lymphoma He p a t oc arcinom a Sk i n non mel anoma Pro s t ate Kapos i Non Hodgk in lym phom a Males: n= 1062 cancer cases Characteristics Median (IQR) ; N (%) Broncho Pulmonary N= 90 Hepato Carcinoma N= 96 Hodgkin Lymphoma N=82 Anal Canal N= 53 Breast N= 54 Colo-Rectal N=38 Prostate N=111 Head And Neck N=54 p Female 21 (23.33) 20 (20.83) 9 (10.98) 12 (22.64) 50 (92.59) 10 (26.32) 0 (0.00) 12 (22.22) <.0001 Male 69 (76.67) 76 (79.17) 73 (89.02) 41 (77.36) 4 (7.41) 28 (73.68) 111 (100.00) 42 (77.78) Age 54 [49 ; 63] 54 [49 ; 58] 45 [39 ; 51] 50 [45 ; 55] 48 [42 ; 58] 57 [50 ; 66] 64 [57 ; 70] 53 [20 ; 59] <.0001 Nadir CD4 cell count/mm 3 144 [38 ; 274] 133 [74 ; 244] 141 [46 ; 243] 96 [23 ; 188] 229 [82 ; 314] 102 [17 ; 219] 175 [98 ; 263] 111 [38 ; 242] 0.004 ≥200/mm 3 34 (37.78) 33 (34.38) 28 (34.15) 12 (22.64) 32 (59.26) 11 (28.95) 46 (41.44) 18 (33.96) 0.01 <200/mm 3 56 (62.22) 63 (65.63) 54 (65.85) 41 (77.36) 22 (40.74) 27 (71.05) 65 (58.56) 35 (66.04) CD4 T cell count/mm 3 506 [273 ; 702] 454 [245 ; 587] 339 [176 ; 563] 408 [217 ; 757] 717 [408 ; 913] 446 [271 ; 659] 511 [344 ; 646] 443 [276 ; 597] <.0001 ≤ 200/mm 3 12 (13.33) 21 (21.88) 24 (29.27) 10 (18.87) 1 (1.85) 5 (13.16) 5 (4.50) 8 (15.09) 0.0002 201- 500/mm 3 33 (36.67) 35 (36.46) 31 (37.80) 20 (37.74) 18 (33.33) 17 (44.74) 46 (41.44) 21 (39.62) > 500/mm 3 45 (50.00) 40 (41.67) 27 (32.93) 23 (43.40) 35 (64.81) 16 (42.11) 60 (54.05) 24 (45.28) CD8 T cell count/mm 3 788 [558 ; 1122] 653 [436 ; 966] 623 [350 ; 918] 848 [571 ;1240] 643 [479 ; 932] 752 [443 ; 974] 720 [500 ; 962] 799 [569 ; 1104] 0.003 CD4:CD8 ratio 0.60 [0.40 ;0.86] 0.64 [0.39 ;0.98] 0.59 [0.34 ;0.80] 0.51 [0.27 ;0.80] 0.97 [0.74 ;1.43] 0.63 [0.39 ;0.56] 0.76 [0.51 ;1.06] 0.48 [0.41 ;0.74] <.0001 <1 74 (83.15) 73 (76.04) 70 (85.37) 47 (90.38) 28 (51.85) 32 (86.49) 74 (66.67) 48 (94.12) <.0001 Table 2- Characteristics of patients with the most frequent Non AIDS-defining cancers Characteristics Median (IQR) ; N (%) PATIENTS WITHOUT INCIDENT CANCER N= 43328 PATIENTS WITH INCIDENT CANCER N=1314 P HIV Follow-up Time (y) 13 [6; 21] 16 [8; 23] <.0001 Female Male 13247(30.57) 30081 (69.43) 296 (22.53) 1018 (77.47) <.0001 Age 48 [40; 55] 52 [46; 61] <.0001 HIV Contamination Route Heterosexual MSM IVDU Others 18514 (43.15) 16481 (38.41) 3409 (7.95) 4501 (10.49) 465 (35.39) 505 (38.43) 222 (16.89) 122 (9.28) <.0001 CDC stage A B C 26477 (61.97) 6544 (15.32) 9702 (22.71) 402 (30.64) 257 (19.59) 653 (49.77) <.0001 HCV coinfection No 36931 (85.24) 988 (75.19) <.0001 Nadir CD4 cell count/mm 3 225 [99; 353] 150 [50; 269] <.0001 ≥200/mm 3 <200/mm 3 23613 (55.72) 18764 (44.28) 512 (39.48) 785 (60.52) <.0001 CD4 T cell count/mm 3 606 [418; 812] 450 [244; 648] <.0001 ≤ 200/mm 3 201- 500/mm 3 2914 (6.90) 12105 (28.67) 254 (19.46) 482 (36.93) <.0001 CD8 T cell count/mm 3 771 [556;1054] 746 [506;1090] 0.017 ≤1000/mm 3 >1000/mm 3 29832 (71.12) 12113 (28.88) 914 (70.52) 382 (29.48) 0.64 CD4:CD8 ratio 0.79[0.51 ;1.13] 0.58[0.33 ;0.9] <.0001 <1 ≥1 27743 (66.18) 14177 (33.82) 1018 (78.61) 277 (21.39) <.0001 HIV viral load (VL) copies/mL 20 [20; 40] 40 [20; 68] <.0001 HIV VL copies/mL ≤ 50 51-1000 1001-10 000 10 001-100 000 >100 001 35230 (83.44) 3337 (7.90) 1301 (3.08) 1596 (3.78) 760 (1.80) 951 (73.04) 155 (11.90) 57 (4.38) 69 (5.30) 70 (5.38) <.0001 Time with HIV- VL<40 (years) 2.5 [0.4; 6.1] 1.5 [0; 4.6] <.0001 ART naive 3829 (8.84) 143 (10.88) 0.01 Antiretroviral treatment 2 NRTI+ boosted-PI 2 NRTI+ 1 NNRTI 2 NRTI+ 1 INSTI Others** 11210 (28.38) 13366 (33.84) 7325 (18.55) 7592 (19.22) 434 (37.09) 315 (26.92) 120 (10.26) 301 (25.73) <.0001 On first-line of ART 6408 (16.22) 161 (13.75) 0.02 Time exposure to ART(y) Time exposure to the last ART(m) 9 [3; 17] 22 [6; 52] 11 [3; 16] 18 [4; 42] 0.37 <.0001 Previous malignant disease 2569 (5.93) 176 (13.39) <.0001 ** SIR [95%CI]=1.08 [0.88-1.32]: W: 1.33 [0.87-2.02]; M: 1.02 [0.81-1.28], calculated aggregating colorectal and anal cases as they were grouped in the general population p-values for test of linear trend p-values for test of linear trend 4. Estimation nationale de l’incidence et de la mortalité par cancer en France sur la période 1980-2012. Étude à partir des registres des cancers du réseau Francim Partie 1 – Tumeurs solides 5. Shiels MS, Engels EA.Curr Opin HIV AIDS. 2017 Jan;12(1):6-11. 0 10 20 30 40 50 2010 2011 2012 2013 2014 2015 Year All Linear fit p=0.884 Men Linear fit p=0.501 Women Linear fit p=0.434 Incidence rates head and neck cancers 60 80 100 120 140 2010 2011 2012 2013 2014 2015 Year Women Linear fit p=0.071 Incidence rates breast cancers 60 80 100 120 IR/100 000 PA 2010 2011 2012 2013 2014 2015 Year Men Linear fit p=0.431 Incidence rates prostate cancers 20 40 60 80 2010 2011 2012 2013 2014 2015 Year All Linear fit p=0.997 Men Linear fit p=0.326 Women Linear fit p=0.505 Incidence rates broncho-pulmonary cancers 0 20 40 60 80 2010 2011 Year All Linear fit p=0.845 Men Linear fit p=0.460 Women Linear fit p=0.069 Incidence rates Hodgkin lymphoma 20 40 60 80 100 2010 2011 2012 2013 2014 2015 Year All Linear fit p=0.781 Men Linear fit p=0.590 Women Linear fit p=0.305 Incidence rates liver cancers 0 20 40 60 80 IR/100 000 PA 2010 2011 2012 2013 2014 2015 Year All Linear fit p=0.925 Men Linear fit p=0.732 Women Linear fit p=0.502 Incidence rates anal cancers 10 20 30 40 IR/100 000 PA 2010 2011 2012 2013 2014 2015 Year All Linear fit p=0.672 Men Linear fit p=0.471 Women Linear fit p=0.694 Incidence rates colorectal cancers 25.0 /105 PY [18.6-33.4] 31.6 /105 PY [24.4-41.0] 45.5/ 105 PY [36.6-56.5] 53.3/ 10 5 PY [43.6-65.1] 30.0/ 105 PY [23.0-39.1] 90.8/ 105 PY [69.0-119.5] 91.1/ 105 PY [75.7-109.5] SIR** SIR [95%CI]=0.56 [0.42-0.73] SIR [95%CI]=0.74 [0.61-0.91] W:1.35 [0.89-2.04];M: 0.66 [0.52-0.82] SIR [95%CI]=0.61 [0.51-0.73] SIR** 54.4/ 105 PY [44.9-66.3] SIR [95%CI]=3.78 [3.08-4.60] W: 12.9 [8.31-20.0]; M: 3.18 [2.54-3.98] SIR [95%CI]=13.8 [11.1-17.1] W: 6.18 [3.22-11.9] M: 16.2 [12.9-20.4] SIR [95%CI]=1.12 [0.86-1.46] W: 2.38 [1.35-4.19]; M: 0.97 [0.72-1.32] References PLWHIV followed-up in the DAT'AIDS cohort between 2010-2015, aged >15 years at baseline N= 44 642 Patients with Incident Cancer N= 1314 Patients with Prevalent Cancer N= 137 Non AIDS- Cancer N= 1082, 989 patients AIDS- Cancer N= 358, 345 patients