Wednesday, October 7, 2009

Non-AIDS-defining cancers now outweigh AIDS-defining cancers in US cohort

A retrospective analysis of 2566 patients in an urban HIV clinic in the US has found that rates of AIDS-defining cancers have declined dramatically since 1996. However, a wide range of other, non-AIDS-defining cancers remain more common in this HIV-positive cohort than in the general population, and now represent a large proportion of the cancers seen in this population. The results, which mirror those of many other recent studies, were reported in the February 19 issue of AIDS. "AIDS-defining" cancers are those which – in an admittedly circular definition – are defined by health authorities as constituting an AIDS diagnosis in persons with HIV. There are currently three in the United States: Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer. Many earlier studies have shown markedly decreased incidences of these AIDS-defining cancers, while many other non-AIDS-defining cancers remain more common or even appear to be on the increase among people with HIV.In this retrospective analysis, clinical records of HIV-positive patients at the Johns Hopkins University AIDS Service – a large urban clinic in Baltimore, Maryland – were analysed for diagnoses of cancer, and their outcomes. The analysis was based on the 2566 patients whose clinic medical records were available for the calendar years from 1996 to 2005, inclusive, for a total of 19,491 person-years of follow-up. This was an urban cohort with a large proportion of black, street-involved, and/or injection drug using (IDU) patients: the cohort was 68% male, 75% black, 48% heterosexual, 29% men who have sex with men (MSM) and 42% IDU, with a median age of 38; 41% were hepatitis C co-infected. The median baseline CD cell count was 281 cells/mm3 and the median viral load was 4.42 log10 copies/ml. AIDS-defining cancers Kaposi's sarcoma was diagnosed in 68 patients (standardised incidence ratio [SIR], 5600; 95% confidence interval [CI], 4400–7200), non-Hodgkin's lymphoma (NHL) in 55 (SIR, 23.1; 95% CI, 17.8–30.0), and cervical cancer in 15 (SIR, 16.6; 95% CI, 9.3–27.4) (where the standardised incidence ratios compare the observed rates to those seen in the general, HIV-negative population). Overall, rates of AIDS-defining cancers (ADCs) decreased from 12.5 cases per 1000 person-years (in 1996) to 3.5 cases per 1000 person-years (in 2005) (p<.001). This decrease was due to decreases in NHL and Kaposi's sarcoma; rates of cervical cancer remained unchanged. Non-AIDS-defining cancers A total of 115 non-AIDS-defining cancers (non-ADCs) were diagnosed in this cohort between 1996 and 2005, for an overall incidence rate of 5.9 per 1000 person-years. The annual incidence rate increased from 3.9 to 7.1 cases per 1000 person-years between 1996 and 2005 – a trend that was not quite statistically significant (p=0.13). The most commonly diagnoses were cancers of the lung (n=29; SIR, 5.5; 95% CI, 3.7–8.0), liver (n=13; SIR, 16.5; 95% CI, 8.8–28.2), anus (n=10; SIR, 39.0; 95% CI, 18.7–71.7), head and neck (n=14; SIR, 5.1; 95% CI, 2.8–8.6), and Hodgkin’s lymphoma (n=8; SIR, 9.8; 95% CI, 4.2–19.2). These rates were 5- to 39-fold higher than comparable rates in the general population. Increased rates (compared to the general population) were also seen for esophageal and bladder cancer and melanoma; risks of breast, prostate and colorectal cancers were not elevated. Other analyses In this cohort, patients with non-ADCs were more likely to be injection drug users (49% vs. 26% with ADCs, p=.001) and to have HCV co-infection (50% vs. 30%, p=.003). They also tended to be older (median 48 vs. 38 years, p<.001) and be less immunosuppressed (CD4 counts 270 vs. 60 cells/mm3, p<.001; history of opportunistic infections 57% vs. 70%, p=.033). Statistically, there was no difference in survival after diagnosis for AIDS-defining and non-AIDS-defining cancers, although the median survival time varied very widely between different types of cancer. For ADCs, older age and lower CD4 count increased the risk of mortality (adjusted hazard ratio 2.21 for age ≥ 50, 95% CI, 1.00–4.89, p=.05; hazard ratio 4.02 for CD4 count ≤ 50 cells/mm3, 95% CI, 1.75–9.26, p=.001). Neither age, race, sex, nor CD4 count were significantly associated with mortality risk for non-ADCs. However, the number of cases was too small to analyse factors affecting incidence or survival for any specific types of cancer. In conclusion, the authors note that the trends observed in this cohort "mirror trends seen nationally." Kaposi's sarcoma and non-Hodgkin's lymphoma, both of which are strongly linked to immune suppression, have become much less common, while rates of cervical cancer and many non-AIDS defining cancers have not declined. As seen in other studies, a number of non-AIDS-defining cancers including anal, lung and liver cancers, and cancers of the head and neck, were more common in this HIV-positive cohort than in the general population. These results "underscore the importance of prevention and early clinical evaluation of patients possibly symptomatic for [the more common non-AIDS-defining cancers]," particularly lung, head and neck, liver and anal cancer.


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