February 6, 2006
Are HIV-infected people at greater risk for cancer? The answer, based on a number of studies, seems to be yes. But how much of a risk remains an ongoing question. Researchers are looking into determining whether the pathways of cancer development are similar in HIV-infected versus HIV-uninfected individuals, identifying how HIV infection affects the risk of developing various cancers as well as the prognosis following cancer onset, and establishing whether highly active antiretroviral therapy (HAART) affects the time to onset and severity of cancers.
Eric Engels and colleagues from the National Cancer Institute in Bethesda, Md., conducted a study in which they assessed the relationship between HIV serostatus and the likelihood of developing Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL) or cervical cancer over time. Called the AIDS Cancer Match Registry Study, the investigators linked data on HIV serostatus with data on cancer status for 375,933 HIV-seropositive individuals using AIDS and cancer registries in 11 regions throughout the United States.
The cancer risks associated with the onset of AIDS were then compared with the risks identified among HIV-seronegative individuals in the general population. The study focused on three major time periods: 1980 to 1989, 1990 to 1995 and 1996 to 2002. The most recent period is commonly regarded as the "HAART era" due to the wide availability and use of three-drug regimens.
The results of this study clearly showed that the risk of developing KS declined substantially over time: When compared with the incidence from 1980 to 1989, the KS rate dropped during the period from 1990 to 1995 and then dropped further during 1996 to 2002 (standardized incidence ratios [SIRs]: 52,900, 22,050 and 3,642, respectively). However, people with AIDS still maintained a higher risk of developing KS compared with persons in the general population. Moreover, the increased risk continued during the HAART era (1996-2002) despite the extensive availability of antiretroviral drugs.
Similar declines were observed for the incidence of NHL among individuals with AIDS (SIRs: 79.8, 53.2 and 22.6 for the three respective time periods). However, an elevated risk for NHL again remained between 1996 and 2002 for HIV-infected individuals when compared with the general population. This was true regardless of whether NHL involved the central nervous system (CNS), although, in the latter case, a larger decrease in the relative risk for CNS NHL was observed during 1996 to 2002.
Interestingly, the risk of cervical cancer did not change significantly over the three time periods evaluated, and the incidence was relatively low in comparison with either KS or NHL (SIRs: 7.7, 4.2 and 5.3 for the three respective time periods).
The diminished rates of KS and NHL over the time periods studied are likely attributable to widespread access to anti-HIV drugs during the HAART era, especially since the most dramatic drops in incidence occurred during the period from 1996 to 2002. The greatest overall impact of HAART was on the incidence of NHL with CNS involvement. Some of the NHL and KS cases that continue to been seen may be due to non-adherence to antiretroviral drug regimens, problems among some marginalized populations in accessing HIV care, and/or the development of HIV drug resistance. Clearly, there are segments of the HIV-infected population that desperately require better drugs for the treatment of both HIV-related disease and associated malignancies.
It should also be pointed out that a related study led by Gregory Kirk from Johns Hopkins University in Baltimore observed that HIV-infected individuals might be at elevated risk of developing lung cancer compared with the general population. Although these observations were made based on a relatively small number of injection drug users included in the ALIVE study (27 individuals died from lung cancer among a cohort of 2,960 injection drug users; 14 of the individuals who died were HIV infected), the trends are alarming and suggest that lung cancer deaths may be increasing among HIV-infected individuals at this time. These trends may in part be due to higher-than-average rates of smoking among the study cohort, which includes the residual risk of lung cancer development among individuals who have given up the habit. However, even once such factors as age, gender and smoking history were taken into consideration, the investigators still found that the lung cancer incidence among HIV-infected individuals was higher than average (relative hazard: 3.04 when compared with HIV-uninfected individuals). This study, as well as that from Engels et al, presents an excellent case for continued follow-up and better access to treatment for HIV-infected individuals at risk of developing cancer malignancies.
These conclusions are further reinforced by data from Pragna Patel and colleagues from the Centers for Disease Control and Prevention, the University of Illinois and the Research Triangle Institute in Atlanta, Ga. Their study, like that by Engels et al, was designed to assess the incidence of malignancies among HIV-infected individuals. Patel et al evaluated both AIDS-associated and non-AIDS-associated malignancies in order to better understand the relationship between cancer development and the presence of HIV disease.
The investigators followed a total of 59,101 individuals from 1992 to 2002 who were included in a variety of data sets. One of these was the HIV Outpatient Study (HOPS), a prospective, observational study that has followed individuals from nine major clinics in eight U.S. cities since 1992. Another was the Adult/Adolescent Spectrum of Disease (ASD) project that has followed over 60,000 patients at 100 facilities in 10 cities between 1990 and 2003. Data from these databases were compared with those from the Surveillance and End Results (SEER) project that tracks cancer incidence and survival in 13 designated areas within the United States.
The investigators observed that the rates of three different AIDS-associated malignancies -- KS, NHL and cervical cancer -- were drastically higher among HIV-infected individuals compared with the general population from the SEER project (adjusted relative risks [RRadj]: 353.7, 28.7 and 17.0, respectively).
In addition, seven different non-AIDS-associated malignancies were also higher among HIV-infected individuals: anal cancer (RRadj [adjusted risk ratio]: 18.3), Hodgkin's disease (RRadj: 17.5), liver cancer (RRadj: 4.5), testicular cancer (RRadj: 3.3), melanoma (RRadj: 2.1), oropharyngeal cancer (RRadj: 2.0) and lung cancer (RRadj: 1.6). In contrast, the rates of both breast cancer and prostate cancer seemed to be reduced among HIV-infected individuals when compared with the SEER population, while no differences in the rates of renal and colorectal cancer were observed between the two populations.
The authors noted that the individuals followed in the HOPS and ASD studies might not be representative of all HIV-infected individuals in the United States. However, they are probably representative of similar groups of HIV-infected individuals. In addition, the authors cautioned that the individuals followed in the SEER project may include more city dwellers than is common among the U.S. population as a whole. Nevertheless, the increased rates of various cancers among HIV-infected individuals identified in the Patel study corroborate the findings from the Engels and Kirk studies.
In conclusion, this study demonstrates that HIV-infected individuals are at increased risk for developing a number of AIDS-associated and non-AIDS-associated malignancies. These findings also substantiate those obtained by Engels et al and Kirk et al regarding the need for appropriate monitoring for malignancies among HIV-infected individuals.
Abstract: HIV infection increases risk for lung cancer mortality independent of smoking (Poster 811)
Authored by: GD Kirk, C Merlo, P O'Driscoll, S Mehta, D Vlahov, J Samet
Affiliations: Johns Hopkins Univ, Baltimore, MD, US; New York Academy of Med, NY, US
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Abstract: Incidence of AIDS defining and non-AIDS defining malignancies among HIV-infected persons (Poster 813)
Authored by: P Patel, D Hanson, R Novak, A Moorman, T Tong, S Holmberg, P Sullivan, J Brooks
Affiliations: CDC, Atlanta, GA, US; Univ of Illinois Coll of Med, Chicago, US; Res Triangle Inst Intl, Atlanta, GA, US
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