1. Non-AIDS cancers Pr. Jean-Philippe SPANO Marianne VEYRI
On behalf of the French CANCERVIH Group
Head Medical Oncology Dpt
Pitié-Salpêtrière Hospital
Paris, France

2. Disclosure form
Consultant or advisory role (fees) or meeting invitation from Roche, BMS, MSD, Pfizer, Lilly, Sanofi, Novartis,PFO, Janssen and Gilead

3. Relative risk (RR) in HIV+ vs HIV- before ART
Cancer
RR (IC 95%)
Lung
2,7 (1,9-3,9)
Hodgkin disease (EBV)
11,0 (8,4-14,4)
Liver (HBV/HCV)
5,2 (3,3-8,2)
Anal canal (HPV)
28,7 (21,6-38,3)
Grulich et al Courtesy of D. Costagliola

4. Main NON-AIDS Cancers (in US)
Uldrick T, NEJM, 2018

5. Temporal evolution of the risk of the most common non-AIDS cancers during the cART period
Lung: ↓ incidence
Decline in the prevalence of smoking (among HIV+ men)
Improved immune control
Decrease in the incidence of recurrent pneumonia and tuberculosis (Shebl et al, 2010; Shiels et al, 2011)
Hodgkin disease: ↓ or no change in incidence according to studies
Liver: ↑incidence (not in US, Hernandez-Ramirez, Lancet HIV 2017)
Long-term exposure to HCV (high prevalence in HIV + population)
Anal canal: ↓ or no change in incidence according to studies
Possibility of cancer development in patients with intraepithelial neoplasia promoted by profound immunosuppression (Costagliola et al, 2013)
Robbins et al, 2014, Hleyhel et al, 2015, Park et al, 2016, courtesy of D. Costagliola

6. Relative risk (RR) in HIV+ vs HIV-
FHDH/France
Hleyhel 2015 US
Robbins 2014
Park 2016
Lung
3 (3-3)
2 (2-2)
Hodgkin disease
27 (23-30)
10 (9-12)
9 (3-28)
Liver
11 (10-12)
3 (3-4)
2 (2-3)
Anal canal
79 (70-90)
32 (28-36)
77 (28-218)
Courtesy of D. Costagliola

7. What is the risk for HIV+ people with a CD4 count >500/mm3?

8. Risk when CD4 ≥ 500/mm3 Kaiser permanente (Silverberg et al, 2011)
RR in HIV+ with last CD4 ≥ 500/mm3, compared to HIV-
Hodgkin
Anal canal
Lung
Liver
13,5
33,8
1,2 1
(7,2-25,1)
(17,8-64,3)
(0,7-1,9)
(0,4-2,4)
FHDH ANRS CO4 (Hleyhel et al, 2014, 2015)
RR in HIV+ with CD4 ≥ 500/mm3 for at least 2 years
Compared to HIV-
Hodgkin
Anal canal
Lung
Liver
9,4 -
0,9
2,4
(7,9-16,8)
(0,6-1,3)
(1,4-4,1)
Courtesy of D. Costagliola

9. And smoking ?

10. The role of smoking
Several studies had suggested that the risk of lung cancer was higher among HIV+, regardless of being a smoker Chaturvedi et al, AIDS 2007; Engels et al, J Clin Oncol 2006; Kirk et al, Clin Infect Dis 2007
A Danish study (Helleberg et al, AIDS 2014) looked at the impact of smoking and HIV infection on the risk of cancer in PLHIV compared to the general population: - Higher risk of cancer among PLHIV  Smoking-related cancers IRR 2.8 ( )  Virus-associated cancers IRR 11.5 ( ) Adjusted for age, sex and tobacco - In non-smokers, only the risk of cancers associated with viruses is high - The risk of other cancers (neither associated with viruses nor smoking) is not higher and is not associated with immunosuppression
Other causes: chronic pulmonary Inf, abnormal Im activation, repeated lung infections

11. Do cancers occur at a younger age among people HIV+?

12. Age distributions are very different between the general population and HIV+

13. Age at cancer occurrence in HIV+ and in the general population after adjustment for age and sex
FHDH/France
Shiels 2010
Sigel 2012
Hleyhel 2014,2015
Lung
-4y (p<10-3)
-2y (p<10-3)
-3y (p<10-4)
Hodgkin
+2y (p<10-3)
-1y (p=0,04)
Liver
-1y (p=0,53) 
-10y (p<10-4) 
Co-infection HBV and/or HCV
-11y (p<10-4)
Neither HBV nor HCV
+2y (p=0,41)
Anal canal
-3y (p<10-3)
-2y (p=0,12)

14. PLWHIV and aging : caution for breast, colon and prostate cancers

15. Survival

16. 5 years OS
87%
48%
16%
65%
19%
17%

17. For better care, the example of the French CancerVIH network

18. CancerVIH database from the cancerVIH network
Cut-off 30 june 2018: national multidisciplinary board accessible in web meeting
488 patients
611 files
92 patients discussed several times
18,9%
67 patients discussed twice
13,7%
17 patients discussed three times
3,5%
4 patients discussed four times
0,8%
4 patients discussed five times

19. Distribution of patients by French regions11
227 12 11 8 1 29 26 5 10 8 11 27 25 38
+ Switzerland 4 31 4

20. Cancers 69,9% of non-AIDS cancers
29% des patients atteints de Kaposi avaient une CV < 20 cp/mL et étaient sous ARV depuis plus de 12 mois le jour de la RCP

21. Main non-AIDS cancers Anal cancer Lung cancer Head and neck cancer
Breast cancer
Colorectal cancer

22. Oncology Rx Outcomes from RCP
Surveillance
Initiation of a new treatment
No change in treatment
Modification of the current treatment
Chemotherapy

23. ART Outcomes from RCP

24. Effect of HIV on CD4 count and effect of HAART and immunotherapy on HIV and cancer cells
Alongi F, Lancet Oncol 2017

25. Immunotherapy in PLWHIV
35 positive reviews for immunotherapy for HIV+ patients with cancer (lung, bladder, kidney cancers, melanoma and Hodgkin)
21 patients received immunotherapy treatment (up to 30 injections of nivolumab or pembrolizumab) with very good clinical and biological tolerance (Le Garff and al, AIDS 2017 ; Lavolé and al. Annals of Oncology 2018)
1 patient with lung cancer saw his HIV-reservoir drastically decrease in the first 6 months under nivolumab (Guihot and al. Annals of Oncology 2017)

26. PD-1 CANCER-HIV National program
Pr. Jean-Philippe SPANO (CANCERVIH, CLIP²) et Pr. Olivier LAMBOTTE
Pr. Brigitte AUTRAN – Dominique COSTAGLIOLA – Dr Amélie GUIHOT - Pr. Christine KATLAMA
Pr Anne-Geneviève MARCELIN
COREVIH-CANCERVIH Group
lung
IFCT
Trial phase2 CHIVA2
A. Lavolé
Hodgkin
Cohort/
Observatory
(other cancers)
ANRS CO24 OncoVIHAC
J.F. Delfraissy
Substudy :
Immunovirological monitoring

27. Education (also for screening and prevention)
Research
Specific clinical trials for PLWHIV
 ANRS CO24 OncoVIHAC cohort for all patients HIV+ treated for cancer by immunotherapy
CHIVA2 trial for patients HIV+ with lung cancer treated by nivolumab
Care
National multidisciplinary board every 2 weeks
Reference centers
CancerVIH network
Information
Website 
Information booklet for patients
National congress every 2 years
Education (also for screening and prevention)
Newsletters for professionals
Specific university degree for the management of cancers in immunocompromised persons