Population-based Patterns of HIV-related Hodgkin Lymphoma in the Greater San Francisco Bay Area:

Transcription

1 Population-based Patterns of HIV-related Hodgkin Lymphoma in the Greater San Francisco Bay Area: Sally Glaser, Ph.D. Christina Clarke, Ph.D. Northern California Cancer Center Margaret Gulley, M.D. University of North Carolina at Chapel Hill Fiona Craig, M.D. University of Pittsburgh Richard Ambinder, M.D., Ph.D. Johns Hopkins University School of Medicine

2 Hodgkin Lymphoma Relatively rare lymphoma (3.0 per 100,000) Most common cancer of late adolescence Infectious precursor suspected Associated with Epstein-Barr virus (EBV) in 1/4-1/3 of cases High survival rate with treatment

3 HIV-Hodgkin Lymphoma Association Association with HIV first reported in 1984 in small case series Aggressive Advanced stage Virulent histologic subtype Association complicated to interpret Hodgkin lymphoma common in young adults HIV population young-adult

4 HIV-Hodgkin Lymphoma Association HIV-AIDS cohort studies Cancer registry-aids registry linkages Established ~ 10-fold excess of Hodgkin lymphoma given HIV Hodgkin lymphoma NOT an AIDSdefining condition

5 Cumulative AIDS Cases Greater Bay Area, * Male Female Total Number of cases 25,646 2,277 27,923 % *Source: California Department of Health Services Office of AIDS

6 AIDS Incidence by Age Group Greater Bay Area, * No. of Cases *Source: California Department of Health Services Office of AIDS

7 AIDS Incidence by Race/Ethnicity Greater Bay Area, * No. of Cases White Black Hispanic Asian/Other *Source: California Department of Health Services Office of AIDS

8 AIDS Incidence by County Greater Bay Area, * No. of Cases Alameda Contra Costa Marin Monterey San Benito San Francisco San Mateo Santa Clara Santa Cruz *Source: California Department of Health Services Office of AIDS

9 Study of HIV-Associated Hodgkin Lymphoma Greater Bay Area Cancer Registry Study of Hodgkin lymphoma All patients with Hodgkin lymphoma Diagnosed July 1988 December 1998 Residents, 9 Greater Bay Area counties

10 Registry Patient Data Year of diagnosis Age at diagnosis Sex Race/ethnicity County of residence Vital status (July, 2001) Cause of death

11 Registry Tumor Data Histologic subtype B-symptoms (e.g., fever, night sweats) Anatomic site (nodal vs extra-nodal) Stage of disease Ann Arbor (Stage I-IV)

12 Additional Tumor Data ( ) Histopathologic rereview Archival tumor tissues, evaluated for EBV EBER in situ hybridization LMP-1 immunohistochemistry

13 Information on HIV/AIDS Routinely collected registry variables SEER EOD HIV/AIDS indicator (since 1990) Underlying cause of death Relevant text Registry paper abstract Paper death certificate Linkage to CA state AIDS registry

14 HIV status HIV-positive Positive HIV/AIDS (SEER EOD) indicator, or AIDS cause of death, or Mention of ARC or HIV or AIDS on registry abstract, or Mention of ARC or HIV or AIDS on death certificate Match with AIDS registry HIV-negative All other

15 % Age distribution Hodgkin Lymphoma Age

16 Demographic Characteristics Hodgkin Lymphoma Sex Male Race/Ethnicity White Black Hispanic Asian/Other Vital Status Alive (7/01) %

17 Tumor Characteristics Hodgkin Lymphoma % Histology (Rye Classification) Nodular Sclerosis Mixed Cellularity Nod. Lymph. Predomin. Lymph. Predominance Lymph. Depletion Not otherwise specified

18 Clinical Characteristics Hodgkin Lymphoma No B-symptoms* Nodal disease Ann Arbor stage I II III IV *missing for n=341 %

19 Tumor Specimens Hodgkin Lymphoma, Not obtained Obtained EBV-positive EBV-negative N %

20 HIV-AIDS status source All Hodgkin patients HIV-positive SEER EOD indicator Registry abstract mention Cause of death Death certificate mention AIDS registry linkage N 1, %

21 HIV-positive Hodgkin Lymphoma Greater Bay Area HIV-positive males HIV-positive females N % 95 5

22 Hodgkin Lymphoma Patients % Males, Age HIV-positive HIV-negative

23 Patient Characteristics, Males HIV-Associated Hodgkin Lymphoma % Race/Ethnicity White Black* Hispanic Asian/Other* HIV-positive HIV-negative * Significantly different from all others at p 0.05

24 Patient Characteristics, Males HIV-Associated Hodgkin Lymphoma County Alameda* Contra Costa* Marin Monterey San Benito San Francisco* San Mateo Santa Clara* Santa Cruz HIV-positive * Significantly different from all others at p 0.05 % HIV-negative

25 Clinical Characteristics, Males HIV-Associated Hodgkin Lymphoma B-symptoms* Extra-nodal* Stage III-IV disease* % HIV-positive HIV-negative *Significantly different from all others at p 0.05 Missing for n=181 Missing for n=47

26 Overall Survival, Males Hodgkin Lymphoma, as of 7/ Proportion surviving HIV-related Hodgkin lymphoma HIV-unrelated Hodgkin lymphoma Months

27 Tumor Characteristics, Males HIV-Associated Hodgkin Lymphoma Histologic subtype Nodular Sclerosis* Mixed Cellularity* Nod. Lymph. Predomin. Lymph. Predomin. Lymph. Depletion* Unspecified* *Significantly different from all others at p 0.05 HIV-pos < % HIV-neg

28 Tumor Characteristics, Males HIV-Associated Hodgkin Lymphoma EBV-positive* HIV-pos 90 % HIV-neg 32 *Significantly different at p 0.05 Based on 532 patients

29 Predictors of HIV-positive Hodgkin Lymphoma Odds Ratios (OR) and 95% Confidence Intervals (CI) years vs other SF county vs other B-symptoms vs none Stage III-IV vs I-II LD hist. vs NS hist Unspec. hist. vs NS EBV+ vs EBV- cells *Adjusted for race, site, mixed cell and lymphocyte predominance histology, and all other variables shown Age/race-Adjusted OR % CI Adjusted * OR Based on 514 of all cases 95% CI

30 Impact of HIV on Incidence of Hodgkin Lymphoma Incidence rates for Hodgkin lymphoma: Overall patient population HIV-negative patient population Compare overall and HIV-negative rates: Difference estimates burden of HIV-related disease

31 Age-Adjusted Incidence Rates* in Males Hodgkin Lymphoma, All Race/Ethnicity Whites HIV-negative Rate 95% CI Rate All men 95% CI Change 12% 11% Blacks Hispanics % 14% * Average annual, per 100,000, age-adjusted to the 1970 US standard

32 Age-Adjusted Incidence Rates* in Males Hodgkin Lymphoma, HIV-negative Rate 95% CI Histologic subtype Nod. Sclerosis Mixed Cell Lymph. Depl Rate All men 95% CI Change 10% 16% 75% * Average annual, per 100,000, age-adjusted to the 1970 US standard

33 Hodgkin Lymphoma Incidence Rates Males, All males HIV-neg males Age Rate per 100,000

34 Hodgkin Lymphoma Incidence Rates Males, Rate per 100,000 Rate per 100, All white males HIV-unrelated white males Age All black males HIV-unrelated black males Age

35 HIV-Associated Hodgkin Lymphoma Males Pre- and Post-HAART Time Period HIV-pos n % HIV-neg n % (pre-haart) (HAART era)

36 % HIV-positive Hodgkin Lymphoma, Males Age '88-'95, pre-haart '96-'98, post-haart

37 HIV-positive Hodgkin Lymphoma Males Pre- and Post-HAART Race/Ethnicity White Black Hispanic* Asian/Other % * Significantly different at p 0.05

38 HIV-positive Hodgkin Lymphoma Males Pre- and Post-HAART B-symptoms Extra-nodal Stage III-IV disease* Missing for n=25 Missing for n=10 * Significantly different at p %

39 1 Overall Survival, Males Hodgkin Lymphoma, , Proportion surviving (pre-haart) (HAART era) Months

40 HIV-positive Hodgkin Lymphoma Males Pre- and Post-HAART Histologic subtype Nodular Sclerosis Mixed Cellularity Nod. Lymph. Predomin Lymph. Depletion Not otherwise specified EBV-positive* * Based on 57 of patients %

41 Study Strengths Taken advantage of HIV/AIDS data in regional cancer registry First detailed surveillance of HIVassociated Hodgkin lymphoma Regional Population-based

42 Study Limitations Lack of validation of HIV identification method Abstracted medical record data for clinical characteristics No individual data on use of HAART EBV information on a proportion of patients

43 Conclusions Consistent findings for HIV-positive Hodgkin lymphoma: Late-stage presentation B-symptoms Non-nodular sclerosis histology Poorer survival Strong association with EBV

44 Conclusions Impact of HIV on regional incidence rates Reflects characteristics of regional HIV population Importance of considering HIV-related disease in geographic variation HAART: Less aggressive Still associated with EBV