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  16th CROI
Conference on Retroviruses and Opportunistic Infections Montreal, Canada
February 8-11, 2009
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Higher Rate of Non-AIDS Infection-Related Cancers With HIV May Be Waning in HAART Era
  16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal
Mark Mascolini
HIV-infected people cared for in California's Kaiser-Permanente healthcare system had significantly higher age- and gender-adjusted rates of non-AIDS cancers than matched Kaiser controls without HIV [1]. The excess risk was particularly high with two infection-related non-AIDS cancers--anal cancer and Hodgkin disease. The infection-related cancer difference between people with and without HIV declined somewhat throughout the HAART era, from 1996 to 2007.
Much work already shows that people with HIV run a higher risk of non-AIDS-defining cancers than uninfected people. Some of this research indicates that HIV-induced immunodeficiency promotes a higher risk of infection-related non-AIDS cancers, including human papillomavirus-related anal and vulvovaginal cancers, hepatitis C-related liver cancer, Epstein-Barr virus-related Hodgkin disease, and Helicobacter pylori-related stomach cancer. To get a better fix on relative rates of infection-related and infection-unrelated cancers in people with HIV in the HAART era, Michael Silverberg and Kaiser colleagues compared the incidence of these cancers in HIV-infected and uninfected people in the Kaiser healthcare system. They hypothesized that HIV-infected patients run a greater risk of infection-related cancers, but that this disparity with the non-HIV group may have waned during the HAART era.
The comparison involved 20,305 people with HIV and 203,050 uninfected controls matched for age, gender, and year. Follow-up (until cancer diagnosis, death, leaving the Kaiser system, or December 31, 2007) averaged 4.2 years in the HIV group and 5.0 years in the control group. Nine in 10 cohort members were men and 74% were gay men; the study group averaged 41 years in age. Silverberg and coworkers split the analysis into three HAART eras: 1996-1999, 2000-2003, and 2004-2007.
The Kaiser team counted 639 cancers in the HIV group (293 infection-related and 346 not) and 3862 cancers in the non-HIV group (486 infection-related and 3376 not). The overall age- and gender-adjusted rate ratio for the HIV group versus the non-HIV group was 7.4 (meaning HIV-infected people had more than a 7 times higher rate of all non-AIDS cancers). Rate ratios were particularly high for the HIV group versus the non-HIV group for anal cancer (80.0), Hodgkin disease (19.4), liver cancer (2.7), and oral cavity/pharyngeal cancers (1.8).
The rate ratio comparing the HIV group with controls fell significantly over the three periods for any infection-related cancer (10 in 1996-1999, 9 in 2000-2003, and 6 in 2004-2007, P = 0.003) but remained significantly higher in the HIV group. The rate ratio for anal cancer and Hodgkin disease when comparing the HIV group with controls also fell over the three periods, but not significantly (P = 0.061 for anal, P = 0.112 for Hodgkin disease).
The age- and gender-adjusted rate ratio for non-AIDS cancers not related to infection was 20% higher with HIV (rate ratio 1.2 , 95% confidence interval [CI] 1.1 to 1.4), including a doubled rate of lung cancers (rate ratio 2.0, 95% CI 1.5 to 2.6). Rates of infection-unrelated cancers rose steeply in the HIV group and the non-HIV group over the three study periods. The adjusted lung cancer rate ratio for HIV-infected people versus controls stood at 4.0 in 1996-1999, dropped to 1.1 in 2000-2003, then rebounded to 2.2 in 2004-2007 (P = 0.007). Compared with the non-HIV group, people with HIV had a higher rate of melanoma and kidney cancer, but not prostate cancer. Data suggested an increased rate of colorectal cancer with HIV versus controls in more recent years (rate ratios 0.6 in 1996-1999, 1.2 in 2000-2003, and 1.4 in 2004-2007, P = 0.24).

Silverberg listed two limitations to the analyses: They did not factor in smoking, CD4 count, or cancer screening practices. And results may not apply to women, uninsured people, or racial/ethnic minorities, all of whom were underrepresented in this population.
The Kaiser team suggested that smaller differences in rate ratios for infection-related cancers in more recent years may reflect improved immune control in the HIV group thanks to better antiretroviral regimens. They proposed that the declining rate ratio difference for lung cancer could also reflect improved immune function in the HIV group or a drop in smoking.
1. Silverberg M, Leyden W, Chao C, et al. Infection-related non-AIDS-defining cancer risk in HIV-infected and -uninfected persons. 16th Conference on Retroviruses and Opportunistic Infections. February 8-11, 2009. Montreal. Abstract 30. (Slide presentation available online at http://www.retroconference.org/2009/data/files/webcast.htm. Click on Monday, then on Prevention and Treatment of Serious OIs and Malignancies, then on Silverberg.)