Download Risk Factors for Development of Anal Cancer in HIV

H-2338
Risk Factors for Development of Anal Cancer in HIV-Infected Men
CONTACT INFORMATION
Phillip A. Cole, M.D.
Clinical Fellow
UC Davis Health System
Division of Infectious Diseases
2315 Stockton Boulevard
Sacramento, CA 95817
phone: (916) 734-3815
fax: (916) 734-7766
[email protected]
Phillip Cole, M.D.1, Wendy Leyden, M.P.H.2, Michael Silverberg, Ph.D., M.P.H.2
1UC Davis Health System, Division of Infectious Diseases, Sacramento, CA,
2Kaiser Permanente Northern California, Division of Research, Oakland, CA.
1. ABSTRACT
Anal Cancer definition
Background: The incidence of anal cancer has increased in the last 20 years and is especially high in HIV-infected
men who have sex with men (MSM). Conflicting data are reported on correlation between duration of infection or
degree of immunosuppression and risk of anal cancer. The goal of this study was to compare the average
duration of infection, CD4 count and viral load among HIV-infected men with and without anal cancer at a
community-based hospital.
 CD4 count closest prior to the index date
 HIV-1 RNA viral load closest prior to the index date
 Duration of infection defined as time from earliest diagnostic evidence of HIV disease (HIV+
antibody test, detectable HIV-1 RNA viral load, or clinical diagnosis with AIDS)
 SEER code that combines histology with primary site: 21060
Outcome variables
UNIVARIATE ANALYSIS
Predictor variables
Methods: Cases included all HIV-positive men at Kaiser Permanente Oakland Medical Center (KPOAK) diagnosed
with anal cancer between 1/1/96 and 12/31/05. For each case, 3 age- and calendar-month matched HIV-positive
men without anal cancer were randomly selected. The index date for controls was the date assigned as receiving
care at KPOAK. For inclusion, patients were required to have at least one CD4 and HIV RNA test in the 12 months
prior to the index date. Multivariate conditional logistic regression adjusted for age, CD4 count, viral load, and
duration of infection.
Results: A total of 15 HIV-infected anal cancer cases and 45 matched controls were identified. Mean CD4 count
was 224.4/mm3 (standard deviation [sd] 139.9/mm3) for cases and 409/mm3 (sd 201.6/mm3) for controls (P=0.001).
Mean viral load was 8718.5 (sd 20223.1 copies/mL) for cases and 9677.2 (sd 22763.4 copies/mL) for controls.
(P=0.44). Duration of HIV infection at the time of cancer diagnosis for cases was 8.0 (sd 3.8) years and for
controls 7.5 (sd 5.34) years (P=0.54). The crude odds ratio for CD4 count < 200/mm3 was 9.1 (CI 1.9-45.4). Other
factors were not significant in univariate analyses. In multivariate analysis, the adjusted odds ratio for CD4 count
< 200/mm3 was 21.9 (CI 2.0-235).
 HIV-infected with anal cancer vs. HIV-infected without anal cancer
 Race (White, non-Hispanic, African-American, Hispanic, Asian, unknown)
 Route of HIV exposure (with hierarchy of Intravenous Drug Use (IVDU), MSM, Heterosexual
contact, unknown)
 AIDS at time of anal cancer diagnosis (yes or no)
 Antiretroviral therapy use (HAART or no HAART)
Statistical analysis
 Two-sided, unpaired t-test performed for CD4 count, HIV-1 RNA viral load, and duration of
infection.
 Conditional logistic regression for multivariate analysis adjusted for age, CD4 count, HIV-1 RNA
viral load, and duration of infection.
4. RESULTS
Conclusions: These data suggest that degree of immunosuppression is an important risk factor for anal cancer in
HIV-infected men. There have been general recommendations to screen all patients with HIV infection with CD4
counts < 500/mm3. This study lends further credence to this recommendation.
5. DISCUSSION
OR
95% CI
P
CD4 count <200 cells/µL
9.14
1.94-43.01
<0.001
HIV-1 RNA viral load <500
copies/mL
1.91
0.55-6.64
0.298
Duration of infection <10 yrs
1.00
0.29-3.49
1.0
White, Non-Hispanic
1.91
0.55-6.64
0.298
MSM
1.52
0.41-5.64
0.531
HAART
0.52
0.15-1.81
0.298
PATIENT CHARACTERISTICS
2. BACKGROUND
Anal cancer is increasing in prevalence and is especially high in HIVinfected men and women and men who have sex with men (MSM).1,2,3
HIV-positive MSM have at least twice the risk of developing anal cancer as
HIV-negative MSM.4
Anal cancer prevalence in the HIV-infected has increased in the HAART
era (post-1996) with a decrease in death secondary to opportunistic
infections and HIV-associated malignancies.5
It has been hypothesized that ongoing immune deficiency, even in the
presence of HAART, has led to increased life-expectancy but has allowed
for progression of HPV-mediated dysplasia to carcinoma.6
Case
Control
N
15
45
Mean Age (yrs)
46
46
n/a
7.99
7.48
0.539
10 (67%)
30 (67%)
1.0
Mean Duration of HIV infection (yrs)
Duration of HIV infection <10 yrs)
Race
10 (67%)
23 (51%)
African American
5 (33%)
15 (33%)
Hispanic
0
3 (7%)
Asian
0
1 (2%)
Unknown
0
3 (7%)
Attributed mode of infection
The relationship of CD4 count, HIV-1 RNA viral load and duration of
infection with risk of development of anal cancer is not entirely clear.
11 (73%)
29 (64%)
IVDU
2 (13%)
5 (11%)
0
11 (24%)
2 (13%)
0
Heterosexual
Unknown
3. METHODS
Study Design
 Retrospective case control study, data from 1/1/1996 to 12/31/2005.
Study population
 All HIV+ Kaiser Permanente Oakland Medical Center (KPOAK) male patients with anal cancer
diagnosis by biopsy or resection.
 Inclusions: a)≥ 18 years of age; b) male sex; c) anal cancer diagnosed after earliest evidence of
HIV diagnosis (index date); d) enrolled to receive care at KPOAK in the month of cancer
diagnosis; e) ≥1 CD4 count and ≥1 HIV-1 RNA viral load test in the 12 months prior to cancer
diagnosis.
P
AIDS
0
16 (36%)
Yes
15 (100%)
29 (64%)
HAART
CD4 count <200 cells/µL
 Patients with HIV infection with low CD4 counts, particularly
MSM, should be screened for anal cancer.
P
21.9
2.0-235
<0.05
6. REFERENCES
 1. Johnson LG, Madeleine MM, Newcomer LM, et al. Anal cancer incidence
and survival: the surveillance, epidemiology, and end results experience,
1973-2000. Cancer 2004; 101:281-8.
 2. Patel P, Hanson DL, Sullivan PS, et al. Incidence of types of cancer among
HIV-infected persons compared with the general population in the United
States, 1992-2003. Ann Intern Med 2008; 148:728-736.
 3. Piketty C, Selinger-Luneman H, Grabar S, et al. Marked increase in the
incidence of invasive anal cancer among HIV-infected patients despite
treatment with combination antiretroviral therapy. AIDS 2008; 22:1203-11.
 4. Goedert JJ, Cote TR, Virgo P, et al. Spectrum of AIDS-associated
malignant disorders. Lancet 1998; 351:1833-9.
0.294
10 (67%)
23 (51%)
Yes
5 (33%)
22 (49%)
224
409
0.001
8 (53%)
5 (11%)
0.001
Mean HIV-1 RNA viral load
(copies/mL)
8718
9677
0.438
HIV-1 RNA <500 copies/mL
10 (67%)
23 (51%)
0.294
CD4 count ≤200 cells/µL
95% CI
* adjusted for age, CD4 count, HIV-1 RNA viral load, and duration of infection
No
Mean CD4 count (cells/µL)
OR
 5. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and
mortality among patients with advanced human immunodeficiency virus
infection: HIV Outpatient Study Investigators. N Engl J Med 1998; 338:850860.
0.007
No
 Consistent with previous reports4, MSM appears to be an
additional risk factor for anal cancer.
MULTIVARIATE ANALYSIS*
0.020
MSM
 All anal cancer cases in this study had a diagnosis of AIDS
vs. 2/3 of the controls, providing further evidence of an
association of immunosuppression and anal cancer risk.
 The exact threshold for screening (e.g. 200 vs. 500 cells/µL)
remains to be established.
0.587
White, non-Hispanic
 The degree of immunosuppression as measured by CD4
count was an important risk factor for anal cancer in HIVinfected men.
Low grade squamous
intraepithelial lesion with
mildly dysplastic cells.
High grade squamous
intraepithelial lesion with
severely dysplastic cells.
Reproduced from Arain S, Walts AE, Thomas E, and
Bose S. CytoJournal 2005; 2:4.
 6. Palefsky JM. Human papillomavirus virus infection in HIV-infected
persons. Top HIV Medicine 2007; 15:130-3.