1. Malignancies in Young People Sophie Herbert, Alison Barbour, Eva Jungmann, Caroline Foster on behalf of the HIV Young Persons Network (HYPNET)

2. Background Malignancies (both AIDS and non-AIDS defining) occur at higher rates in adults with HIV Data is limited in young people with HIV Malignancies in young people (aged 15-24) in the general population are rare (<1% of total cancer diagnoses) but have increased by 1/5 since mid-1990s 1 Lymphomas, carcinomas and germ-cell tumours account for more than half of all cancer diagnoses in young people 1.Cancer Research UK (2013) Cancer Statistics Report: Teenage and Young Adult Cancer

3. Teenage and Young Adult Cancers by Cancer Type, Average Number of New Cases per Year, Age 15-24, UK, 2000-2009

4. CHIPS cohort data: Vertically infected HIV positive children UK 1996- 2012 2 2. CHIPS- Collaborative HIV Paediatric Study www.chiva.org.uk

5. Background A greater number of children with HIV survive into adulthood the length of time that these young people have been immunosuppressed raises concerns regarding malignancy risk Presentation may also differ from in adults.

6. Method HIV positive young people aged 13-24 years with a malignancy diagnosed between 2000-2014 inclusive were identified Anonymised data was collected: – demographics – type of malignancy – CD4 and VL at time of malignancy diagnosis and in the preceeding 1 year – CD4 nadir – antiretroviral therapy (ART) both past and current – outcomes (HIV and malignancy) – whether the offer of sperm/egg storage had been made/recorded.

7. Results 15/70 centres replied and reported 32 cases. CHIPS database identified a further 8 cases 12 (30 %) had acquired HIV sexually 25 had acquired HIV perinatally (PaHIV) In 3 lymphoma cases and one Kaposis sarcoma case the route of transmission was unknown.

8. 15/70 centres reported 32 cases, 8 identified from CHIPS 12 (30 %) acquired HIV sexually (sHIV) and 25 (62.5%) acquired HIV perinatally (PaHIV). 3 cases (lymphoma and KS) unknown transmission route Results PaHIV (n=25) [IQR]sHIV (n=12, 3 no data)[IQR] SexMale Female Total 19 (76) 6 (24) 25 9 (75) 3 (25) 12 (3 no data) Age at malignancy diagnosis (years)17 [15,20]23 [22,24] Age at HIV diagnosis6 [1.0,11.5]22 [20.75,23.25] CD4 at malignancy diagnosis350 [156.25,567.50]274 [211.5,330.0] CD4 nadir180 [119,358]Not available

9. 15/70 centres reported 32 cases, 8 identified from CHIPS 12 (30 %) acquired HIV sexually (sHIV) and 25 (62.5%) acquired HIV perinatally (PaHIV). 3 cases (lymphoma and KS) unknown transmission route Results PaHIV (n=25) [IQR]sHIV (n=12, 3 no data)[IQR] SexMale Female Total 19 (76) 6 (24) 25 9 (75) 3 (25) 12 (3 no data) Age at malignancy diagnosis (years)17 [15,20]23 [22,24] Age at HIV diagnosis6 [1.0,11.5]22 [20.75,23.25] CD4 at malignancy diagnosis350 [156.25,567.50]274 [211.5,330.0] CD4 nadir180 [119,358]Not available

10. 15/70 centres reported 32 cases, 8 identified from CHIPS 12 (30 %) acquired HIV sexually (sHIV) and 25 (62.5%) acquired HIV perinatally (PaHIV). 3 cases (lymphoma and KS) unknown transmission route Results PaHIV (n=25) [IQR]sHIV (n=12, 3 no data)[IQR] SexMale Female Total 19 (76) 6 (24) 25 9 (75) 3 (25) 12 (3 no data) Age at malignancy diagnosis (years)17 [15,20]23 [22,24] Age at HIV diagnosis6 [1.0,11.5]22 [20.75,23.25] CD4 at malignancy diagnosis350 [156.25,567.50]274 [211.5,330.0] CD4 nadir180 [119,358]Not available

11. 15/70 centres reported 32 cases, 8 identified from CHIPS 12 (30 %) acquired HIV sexually (sHIV) and 25 (62.5%) acquired HIV perinatally (PaHIV). 3 cases (lymphoma and KS) unknown transmission route Results PaHIV (n=25) [IQR]sHIV (n=12, 3 no data)[IQR] SexMale Female Total 19 (76) 6 (24) 25 9 (75) 3 (25) 12 (3 no data) Age at malignancy diagnosis (years)17 [15,20]23 [22,24] Age at HIV diagnosis6 [1.0,11.5]22 [20.75,23.25] CD4 at malignancy diagnosis350 [156.25,567.50]274 [211.5,330.0] CD4 nadir180 [119,358]Not available

12. Results - malignancy diagnoses Malignancy diagnosisPaHIV N (%) SHIV N (%) LymphomaNon-Hodgkins Hodgkins CNS Lymphoma Total 13 (50) 5 (21) 1 (4) 19 3 (20) 0 (0) 1 (7) 4 Kaposis sarcoma3 (13)11 (73) Disseminated adenocarcinoma1 (4)0 Astrocytoma1 (4)0 Hepatocellular carcinoma (HBV co-infected)1 (4)0 Total2515

13. Results - malignancy diagnoses Malignancy diagnosisPaHIV N (%) SHIV N (%) LymphomaNon-Hodgkins Hodgkins CNS Lymphoma Total 13 (50) 5 (21) 1 (4) 19 3 (20) 0 (0) 1 (7) 4 Kaposis sarcoma3 (13)11 (73) Disseminated adenocarcinoma1 (4)0 Astrocytoma1 (4)0 Hepatocellular carcinoma (HBV co-infected)1 (4)0 Total2515

14. Results - malignancy diagnoses Malignancy diagnosisPaHIV N (%) SHIV N (%) LymphomaNon-Hodgkins Hodgkins CNS Lymphoma Total 13 (50) 5 (21) 1 (4) 19 3 (20) 0 (0) 1 (7) 4 Kaposis sarcoma3 (13)11 (73) Disseminated adenocarcinoma1 (4)0 Astrocytoma1 (4)0 Hepatocellular carcinoma (HBV co-infected)1 (4)0 Total2515

15. Distribution of malignancy diagnoses 2000-2014 in 13-24 year olds

16. Detectable Viral load at malignancy diagnosis: (those with data available) 11/19 with PaHIV 8/10 of those with sHIV 5 of these were diagnosed with HIV at the time of malignancy diagnosis Viral load data ART data Median number of antiretroviral regimen prior to malignancy: 2 [1,3.5] for PaHIV 0 [0,1] for sHIV (5 were diagnosed with HIV at the same time as malignancy Of the 15 PaHIV with data available, 8 (53%) had at least 2 class resistance (NRTI and NNRTI).

17. Detectable Viral load at malignancy diagnosis: (those with data available) 11/19 with PaHIV 8/10 of those with sHIV 5 of these were diagnosed with HIV at the time of malignancy diagnosis Viral load data ART data Median number of antiretroviral regimen prior to malignancy: 2 [1,3.5] for PaHIV 0 [0,1] for sHIV (5 were diagnosed with HIV at the same time as malignancy Of the 15 PaHIV with data available, 8 (53%) had at least 2 class resistance (NRTI and NNRTI).

18. Outcomes PaHIVsHIV Prior AIDS diagnosis10/21 (47%)0 Median time from presentation to diagnosis [IQR] 8 weeks [4,10] Delay in diagnosis probable9/14 (63%)5/12 (42%) Median length of follow up post malignancy [IQR] 50 months [18.8,88.5] Malignancy outcome:Remission Active disease Died >5 year survival 10/15 (66.7%) 3 2* 10/21 (47.6%) No data available HIV outcomeUndetectable VL Died No data 14/15 2 6 9/12 2 1 Sperm/egg storage offered?2/21 documentedNo data available * disseminated adenocarcinoma and plasmablastic lymphoma

19. Outcomes PaHIVsHIV Prior AIDS diagnosis10/21 (47%)0 Median time from presentation to diagnosis [IQR] 8 weeks [4,10] Delay in diagnosis probable9/14 (63%)5/12 (42%) Median length of follow up post malignancy [IQR] 50 months [18.8,88.5] Malignancy outcome:Remission Active disease Died >5 year survival 10/15 (66.7%) 3 2* 10/21 (47.6%) No data available HIV outcomeUndetectable VL Died No data 14/15 2 6 9/12 2 1 Sperm/egg storage offered?2/21 documentedNo data available * disseminated adenocarcinoma and plasmablastic lymphoma

20. Outcomes PaHIVsHIV Prior AIDS diagnosis10/21 (47%)0 Median time from presentation to diagnosis [IQR] 8 weeks [4,10] Delay in diagnosis probable9/14 (63%)5/12 (42%) Median length of follow up post malignancy [IQR] 50 months [18.8,88.5] Malignancy outcome:Remission Active disease Died >5 year survival 10/15 (66.7%) 3 2* 10/21 (47.6%) No data available HIV outcomeUndetectable VL Died No data 14/15 2 6 9/12 2 1 Sperm/egg storage offered?2/21 documentedNo data available * disseminated adenocarcinoma and plasmablastic lymphoma

21. Outcomes PaHIVsHIV Prior AIDS diagnosis10/21 (47%)0 Median time from presentation to diagnosis [IQR] 8 weeks [4,10] Delay in diagnosis probable9/14 (63%)5/12 (42%) Median length of follow up post malignancy [IQR] 50 months [18.8,88.5] Malignancy outcome:Remission Active disease Died >5 year survival 10/15 (66.7%) 3 2* 10/21 (47.6%) No data available HIV outcomeUndetectable VL Died No data 14/15 2 6 9/12 2 1 Sperm/egg storage offered?2/21 documentedNo data available * disseminated adenocarcinoma and plasmablastic lymphoma

22. For PaHIV where data was available median follow-up post malignancy was 50 months [18.8,88.5]. 10/15 achieved remission at 1 year, 3 continued to have active disease and 2 died (disseminated adenocarcinoma and plasmablastic lymphoma). 10/21 had >5 year current survival. Sperm/egg storage 2/21 patients who received chemotherapy had egg/sperm storage. These were both Pa HIV. HIV outcomes For PaHIV cases 14/15 patients with data available were undetectable on ART (6 had no data) at last follow-up. For sHIV cases 9/12 were undetectable, 2 died and for one data was missing

23. Discussion Lymphoma was the predominant malignancy seen in PaHIV, while Kaposis Sarcoma predominated in those with sexually acquired HIV. VL suppression prior to malignancy diagnosis was poor, but malignancy and HIV outcomes appear good in the short to medium term. Adherence support and prompt investigation of symptoms is paramount in this group of young people living with HIV. Limitations of this study include the low response rate from HYPNET member clinics and the liklihood that even with a 100% response rate patients seen in some adult services may be missed.

24. Thanks To all HYPNET members With particular thanks to: Alessia Dalla Pria, Mark Bower- Chelsea and Westminster Hospital Caroline Foster - Imperial College Healthcare Sophie Herbert, Eva Jungmann, Tabitha Peake – Mortimer Market Centre Katie Conway - Guys and St Thomas NHS Trust Deborah Williams – Claude Nicol Centre,Brighton Fiona Thompson - Northampton General Hospital Deirdre Redmond - Beaumont Hospital, Dublin Susan Liebeschuetz - Barts and the London Margaret Kingston – Manchester Centre for Sexual Health Emily Cheserem – Kings College Hospital Alison Barbour, Katia Prime – St George’s Hospital Ali Judd, Jeannie Collins – Medical Research Council And Colin Ball for presenting these slides at short notice! Any questions please email: sophieherbert@nhs.net