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Anal Cancers Among HIV-Infected Persons: HAART Is Not Slowing Rising Incidence. Nancy Crum-Cianflone, MD, MPH K. Huppler Hullsiek PhD, A. Weintrob MD, A. Ganesan MD, V. Marconi MD, R.V. Barthel MD, S. Fraser MD, B. Agan MD, and the Infectious Disease Clinical Research Program, Bethesda, MD, USA.
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Anal Cancers Among HIV-Infected Persons: HAART Is Not Slowing Rising Incidence Nancy Crum-Cianflone, MD, MPH K. Huppler Hullsiek PhD, A. Weintrob MD, A. Ganesan MD, V. Marconi MD, R.V. Barthel MD, S. Fraser MD, B. Agan MD, and the Infectious Disease Clinical Research Program, Bethesda, MD, USA
Background • Cancers are increasingly important among HIV-infected persons1-3 • Several cancers are associated with viral co-infections • Human papillomavirus (HPV) can lead to anal squamous cell cancer4-5 1. Patel P, Hanson DL, Sullivan PS, et al. Ann Intern Med. 2008;148:728-36.; 2. Engels EA, Pfeiffer RM, Goedert JJ, et al. AIDS. 2006;20:1645-54.; 3. Crum-Cianflone N, Hullsiek KH, Marconi V, et al. AIDS. 2009; 23:41-50.; 4. Palefsky J. Curr HIV/AIDS Rep. 2008;5:78-85.; 5. Haga T, Kim SH, Jensen RH, et al. JAIDS. 2001;26:256-62.
Background • Anal cancer is uncommon in the general population1,2 • 1.4 cases per 100,000 person-years1 • HIV infected persons have a higher risk of anal cancer3-6 • Further data on the role of HAART and HIV duration on anal cancer is needed 1. SEER Cancer Statistics Review, 1975-2006, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2006. 2. Melbye M, Rabkin C, Frisch M, Biggar RJ. Am J Epidemiol. 1994;139:772-80.; 3. D’Souza G, Wiley DJ, Li X, et al. JAIDS. 2008;48:491-9.; 4. Piketty C, Selinger-Leneman H, et al. AIDS. 2008;22:1203-11.; 5. Diamond C, Taylor TH, Aboumrad T, et al. Sex Transm Dis. 2005;32:314-20.; 6. Chiao EY, Krown SE, Stier EA, et al. JAIDS. 2005;40:451-5.
Methods • U.S. Military Natural History Study, following participants from 1985-2008 • 4,901 HIV-infected participants • 55% with documented seroconversion dates • Anal cancer cases were histopathologically confirmed squamous cell carcinomas
Methods • Data collected included: • Demographics • Medical conditions including STIs • Sequential CD4 counts and HIV RNA levels • Antiretroviral prescription dates • Data were collected every 6 months
Statistical Analyses • Descriptive statistics • Medians presented with interquartile ranges (IQR) • Poisson regression models to calculate age-adjusted rates (per 100,000 PY) and rate ratios • Cox proportional hazard models to evaluate factors associated with anal cancer • Adjusted for year of HIV diagnosis
Results (N=4,901 Evaluated) • 40,951 person years (PY) of follow-up • Characteristics at HIV diagnosis: • Age: 28 years (IQR 24-34) • 92% male • 45% African American and 43% Caucasian • CD4 count: 506 cells/mm3 (IQR 350-676)
Age-Adjusted Incidence Rates of Anal Cancer1 1 For males
Age-Adjusted Incidence Rates of Anal Cancer1 1 For males
By Calendar Period (compared to pre-HAART era) By Duration of HIV Infection(compared to first 5 years) P <0.001 P=0.02 P=0.27 P=0.96 HAARTERA 5-10Years 10-15 Years 15+Years Rate Ratios
Factors Associated with Anal Cancer 1 Time-updated covariate
Multivariate Analyses of Factors Associated with Anal Cancer 1 Time-updated covariate
Study Limitations • Limited number of anal cancers • No information on HPV co-infection • Lack of data on sexual preference • Possibility of unmeasured confounders
Study Strengths • 24 years of data spanning the HIV epidemic • Study focused on single cancer type • Squamous cell anal cancer • Precise data on sequential CD4 counts, duration of HIV infection, and dates of HAART use
Summary • The rates of anal cancer have progressively increased over the HIV epidemic • Longer duration of HIV was associated with higher rates of anal cancer • Nadir CD4 cell count and a prior AIDS event were associated with anal cancer • The use of HAART had no association with anal cancer
Conclusions • These data suggests that anal cancer rates may continue to increase in the HAART era • Preventive strategies for anal cancer among HIV-infected persons are needed
Acknowledgements • Study Participants • Infectious Disease Clinical Research Program (IDCRP) • Uniformed Services University of the Health Sciences, Bethesda, MD, USA • National Institutes of Allergy and Infectious Diseases (NIAID)