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      Spectrum of cancer risk among HIV-infected people in the United States during the modern antiretroviral therapy era: a population-based registry linkage study

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      , MS * , , , PhD * , , PhD , , MD *
      The lancet. HIV

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          Abstract

          Background

          Monitoring cancer risk among HIV-infected people in the modern antiretroviral therapy (ART) era is critical given their elevated risk for many cancers and prolonged survival with immunosuppression, ART exposure, and aging. Our study described cancer risk in HIV-infected people in the United States relative to the general population.

          Methods

          Utilizing data from linked population-based HIV and cancer registries (nine areas; 1996–2012), we calculated standardized incidence ratios (SIRs). We tested SIR differences by AIDS status and over time using Poisson regression.

          Findings

          Among 448,258 HIV-infected people, risk was elevated (p<0·0001) for cancer overall (SIR 1·69; 95%CI: 1·67–1·72), AIDS-defining cancers (Kaposi sarcoma [498; 478–519], non-Hodgkin lymphoma [11·5; 11·1–11·9], and cervix [3·24; 2·94–3·56]), most other virus-related cancers (e.g., anus [19·1; 18·1–20·0], liver [3·21; 3·02–3·41], and Hodgkin lymphoma [7·70; 7·20–8·23]), and some virus-unrelated cancers (e.g., lung [1·97; 1·89–2·05]), but not for other common cancers. Risk for several cancers was higher after AIDS onset and declined across calendar periods. After multivariable adjustment, SIRs decreased significantly across 1996–2012 for six cancers (Kaposi sarcoma, two non-Hodgkin lymphoma subtypes, anus, liver, and lung) but remained elevated in the latest period. SIRs did not increase over time for any cancer.

          Interpretation

          Risks for several virus-related cancers and lung cancer declined among HIV-infected people, likely reflecting ART expansion since 1996. Despite declines, risk for many cancers remain elevated in the modern treatment era.

          Funding

          National Cancer Institute.

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          Most cited references22

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          Tobacco smoking and cancer: a meta-analysis.

          We conducted a systematic meta-analysis of observational studies on cigarette smoking and cancer from 1961 to 2003. The aim was to quantify the risk for 13 cancer sites, recognized to be related to tobacco smoking by the International Agency for Research on Cancer (IARC), and to analyze the risk variation for each site in a systematic manner. We extracted data from 254 reports published between 1961 and 2003 (177 case-control studies, 75 cohorts and 2 nested case-control studies) included in the 2004 IARC Monograph on Tobacco Smoke and Involuntary Smoking. The analyses were carried out on 216 studies with reported estimates for 'current' and/or 'former' smokers. We performed sensitivity analysis, and looked for publication and other types of bias. Lung (RR = 8.96; 95% CI: 6.73-12.11), laryngeal (RR = 6.98; 95% CI: 3.14-15.52) and pharyngeal (RR = 6.76; 95% CI: 2.86-15.98) cancers presented the highest relative risks (RRs) for current smokers, followed by upper digestive tract (RR = 3.57; 95% CI: 2.63-4.84) and oral (RR = 3.43; 95% CI: 2.37-4.94) cancers. As expected, pooled RRs for respiratory cancers were greater than the pooled estimates for other sites. The analysis of heterogeneity showed that study type, gender and adjustment for confounding factors significantly influence the RRs estimates and the reliability of the studies. Copyright 2007 Wiley-Liss, Inc.
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            Cancer burden in the HIV-infected population in the United States.

            Effective antiretroviral therapy has reduced the risk of AIDS and dramatically prolonged the survival of HIV-infected people in the United States. Consequently, an increasing number of HIV-infected people are at risk of non-AIDS-defining cancers that typically occur at older ages. We estimated the annual number of cancers in the HIV-infected population, both with and without AIDS, in the United States. Incidence rates for individual cancer types were obtained from the HIV/AIDS Cancer Match Study by linking 15 HIV and cancer registries in the United States. Estimated counts of the US HIV-infected and AIDS populations were obtained from Centers for Disease Control and Prevention surveillance data. We obtained estimated counts of AIDS-defining (ie, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) and non-AIDS-defining cancers in the US AIDS population during 1991-2005 by multiplying cancer incidence rates and AIDS population counts, stratified by year, age, sex, race and ethnicity, transmission category, and AIDS-relative time. We tested trends in counts and standardized incidence rates using linear regression models. We multiplied overall cancer rates and HIV-only (HIV infected, without AIDS) population counts, available from 34 US states during 2004-2007, to estimate cancers in the HIV-only population. All statistical tests were two-sided. The US AIDS population expanded fourfold from 1991 to 2005 (96,179 to 413,080) largely because of an increase in the number of people aged 40 years or older. During 1991-2005, an estimated 79 656 cancers occurred in the AIDS population. From 1991-1995 to 2001-2005, the estimated number of AIDS-defining cancers decreased by greater than threefold (34,587 to 10,325 cancers; P(trend) < .001), whereas non-AIDS-defining cancers increased by approximately threefold (3193 to 10,059 cancers; P(trend) < .001). From 1991-1995 to 2001-2005, estimated counts increased for anal (206 to 1564 cancers), liver (116 to 583 cancers), prostate (87 to 759 cancers), and lung cancers (875 to 1882 cancers), and Hodgkin lymphoma (426 to 897 cancers). In the HIV-only population in 34 US states, an estimated 2191 non-AIDS-defining cancers occurred during 2004-2007, including 454 lung, 166 breast, and 154 anal cancers. Over a 15-year period (1991-2005), increases in non-AIDS-defining cancers were mainly driven by growth and aging of the AIDS population. This growing burden requires targeted cancer prevention and treatment strategies.
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              Cancer risk in people infected with human immunodeficiency virus in the United States.

              Data are limited regarding cancer risk in human immunodeficiency virus (HIV)-infected persons with modest immunosuppression, before the onset of acquired immunodeficiency syndrome (AIDS). For some cancers, risk may be affected by highly active antiretroviral therapy (HAART) widely available since 1996. We linked HIV/AIDS and cancer registries in Colorado, Florida and New Jersey. Standardized incidence ratios (SIRs) compared cancer risk in HIV-infected persons (initially AIDS-free) during the 5-year period after registration with the general population. Poisson regression was used to compare incidence across subgroups, adjusting for demographic factors. Among 57,350 HIV-infected persons registered during 1991-2002 (median CD4 count 491 cells/mm(3)), 871 cancers occurred during follow-up. Risk was elevated for Kaposi sarcoma (KS, SIR 1,300 [n = 173 cases]), non-Hodgkin lymphoma (NHL, 7.3 [n = 203]), cervical cancer (2.9 [n = 28]) and several non-AIDS-defining malignancies, including Hodgkin lymphoma (5.6 [n = 36]) and cancers of the lung (2.6 [n = 109]) and liver (2.7 [n = 14]). KS and NHL incidence declined over time but nonetheless remained elevated in 1996-2002. Incidence increased in 1996-2002 compared to 1991-1995 for Hodgkin lymphoma (relative risk 2.7, 95%CI 1.0-7.1) and liver cancer (relative risk infinite, one-sided 95%CI 1.1-infinity). Non-AIDS-defining cancers comprised 31.4% of cancers in 1991-1995, versus 58.0% in 1996-2002. For KS and NHL, risk was inversely related to CD4 count, but these associations attenuated after 1996. We conclude that KS and NHL incidence declined markedly in recent years, likely reflecting HAART-related improvements in immunity, while incidence of some non-AIDS-defining cancers increased. These trends have led to a shift in the spectrum of cancer among HIV-infected persons. (c) 2008 Wiley-Liss, Inc.
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                Author and article information

                Journal
                101645355
                43213
                Lancet HIV
                Lancet HIV
                The lancet. HIV
                2405-4704
                2352-3018
                20 August 2017
                10 August 2017
                November 2017
                01 November 2018
                : 4
                : 11
                : e495-e504
                Affiliations
                [* ]Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD [Raúl U. Hernández-Ramírez, MS; Meredith S. Shiels, PhD; Eric A. Engels, MD]
                []Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, New Haven, CT [Raúl U. Hernández-Ramírez, MS; Professor Robert Dubrow, PhD]
                Author notes
                [] Corresponding author: Raúl U. Hernández-Ramírez, MS. Department of Chronic Disease Epidemiology, Yale School of Public Health, P.O. Box 208034, New Haven, CT 06520-8034, raul.hernandezramirez@ 123456yale.edu
                Article
                NIHMS900120
                10.1016/S2352-3018(17)30125-X
                5669995
                28803888
                9b0d6c4a-4da2-4991-9e7d-0b949cb89ab2

                This manuscript version is made available under the CC BY-NC-ND 4.0 license.

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