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      Overview of cancer incidence and mortality among people living with HIV/AIDS in British Columbia, Canada: Implications for HAART use and NADM development

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          Abstract

          Background

          The objective of this study is to evaluate the incidence of non-AIDS defining malignancies (NADMs) among people living with HIV/AIDS (PLWHA) in British Columbia, focusing on clinical correlates, highly active antiretroviral therapy (HAART) use, and survival, in order to elucidate mechanisms for NADM development.

          Methods

          A retrospective population based analysis was carried out for individuals with HIV/AIDS that began their treatment between 1996 and 2008.

          Results

          There were 145 (2.95%) NADMs and 123 (2.50%) AIDS defining malignancies (ADMs) identified in 4918 PLWHA in the study population. NADMs were represented by a range of cancer types including, most commonly, lung cancer, followed by anal, breast, head/neck, prostate, liver, rectal, and renal cancers. PLWHA had a SIR of 2.05 (CI:1.73, 2.41) for the development of NADMs compared to individuals without an HIV/AIDS diagnosis in the general population. Independent factors significantly associated with a NADM were: male gender, older age, lower CD4 cell counts, previous NADM, absence of HAART (non-HAART versus HAART) and treatment during the early-HAART era (before 2000 versus after 2000).

          Conclusions

          NADMs represent an important source of morbidity for PLWHA. Use of HAART with its associated improvement in immune-restoration, and tailored targeted cancer screening interventions, may be beneficial and improve outcomes in this unique patient population.

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          Most cited references28

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          Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome.

          Human papillomavirus (HPV)-associated anogenital malignancies occur frequently in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). The purpose of our study was to determine if the high frequency of these cancers is due to lifestyle factors associated with both HPV and HIV infections or to immunosuppression following HIV infection. We studied invasive and in situ HPV-associated cancers among 309 365 U.S. patients with HIV infection/AIDS (257 605 males and 51 760 females) from 5 years before the date of AIDS onset to 5 years after this date. Sex-, race-, and age-standardized ratios of observed-to-expected cancers served as measures of relative risk (RR). Trend tests were used to evaluate changes in the RRs during the 10 years spanning AIDS onset. All statistical tests were two-sided. All HPV-associated cancers in AIDS patients occurred in statistically significant excess compared with the expected numbers of cancers. For in situ cancers, overall risks were significantly increased for cervical (RR = 4.6; 95% confidence interval [CI] = 4.3-5.0), vulvar/vaginal (RR = 3.9; 95% CI = 2.0-7. 0), anal (in females, RR = 7.8 [95% CI = 0.2-43.6]; in males, RR = 60.1 [95% CI = 49.2-72.7]), and penile (RR = 6.9; 95% CI = 4.2-10.6) cancers, and RRs increased during the 10 years spanning AIDS onset for carcinomas in situ of the cervix (P: for trend <.001), vulva/vagina (P: for trend =.04), and penis (P: for trend =.04). For invasive cancers, overall risks were significantly increased for cervical (RR = 5.4; 95% CI = 3.9-7.2), vulvar/vaginal (RR = 5.8; 95% CI = 3.0-10.2), and anal (RR = 6.8; 95% CI = 2.7-14.0) cancers in females and for anal (RR = 37.9; 95% CI = 33.0-43.4), penile (RR = 3. 7; 95% CI = 2.0-6.2), tonsillar (RR = 2.6; 95% CI = 1.8-3.8), and conjunctival (RR = 14.6; 95% CI = 5.8-30.0) cancers in males. However, RRs for invasive cancers changed little during the 10 years spanning AIDS onset. HPV-associated malignancies occur at increased rates in persons with HIV/AIDS. Increasing RRs for in situ cancers to and beyond the time of AIDS onset may reflect the gradual loss of control over HPV-infected keratinocytes with advancing immunosuppression. However, the lack of a similar increase for invasive HPV-associated cancers suggests that late-stage cancer invasion is not greatly influenced by immune status.
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            HIV and aging: time for a new paradigm.

            The population of patients with HIV infection achieving viral suppression on combination antiretroviral therapy is growing, aging, and experiencing a widening spectrum of non-AIDS diseases. Concurrently, AIDS-defining conditions are becoming less common and are variably associated with outcome. Nonetheless, the spectrum of disease experienced by those aging with HIV remains strongly influenced by HIV, its treatment, and the behaviors, conditions, and demographics associated with HIV infection. Our focus must shift from a narrow interest in CD4 counts, HIV-RNA, and AIDS-defining illnesses to determining the optimal management of HIV infection as a complex chronic disease in which the causes of morbidity and mortality are multiple and overlapping. We need a new paradigm of care with which to maximize functional status, minimize frailty, and prolong life expectancy. A composite index that summarizes a patient's risk of morbidity and mortality could facilitate this work and help chart its progress.
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              HIV as an independent risk factor for incident lung cancer.

              It is unclear whether the elevated rate of lung cancer among HIV-infected persons is due to biological effects of HIV, surveillance bias, or excess smoking. We compared the incidence of lung cancer between HIV-infected and demographically similar HIV-uninfected patients, accounting for smoking and stage of lung cancer at diagnosis. Data from the Veterans Aging Cohort Study Virtual Cohort were linked to data from the Veterans Affairs Central Cancer Registry, resulting in an analytic cohort of 37,294 HIV-infected patients and 75,750 uninfected patients. We calculated incidence rates of pathologically confirmed lung cancer by dividing numbers of cases by numbers of person-years at risk. We used Poisson regression to determine incidence rate ratios (IRRs), adjusting for age, sex, race/ethnicity, smoking prevalence, previous bacterial pneumonia, and chronic obstructive pulmonary disease. The incidence rate of lung cancer in HIV-infected patients was 204 cases per 100,000 person-years [95% confidence interval (CI) 167-249] and among uninfected patients was 119 cases per 100,000 person-years (95% CI 110-129). The IRR of lung cancer associated with HIV infection remained significant after multivariable adjustment (IRR 1.7; 95% CI 1.5-1.9). Lung cancer stage at presentation did not differ between HIV-infected and uninfected patients. In our cohort of demographically similar HIV-infected and uninfected patients, HIV infection was an independent risk factor for lung cancer after controlling for potential confounders including smoking. The similar stage distribution between the two groups indicated that surveillance bias was an unlikely explanation for this finding.
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                Author and article information

                Contributors
                c.chiu222@yahoo.ca
                dmsmith@sfu.ca
                ksalters@cfenet.ubc.ca
                wzhang@cfenet.ubc.ca
                skanters@sfu.ca
                dmilan@cfenet.ubc.ca
                jmontaner@cfenet.ubc.ca
                acoldman@bccancer.bc.ca
                bobhogg@cfenet.ubc.ca
                604 806 9108 , smwiseman@providencehealth.bc.ca
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                14 April 2017
                14 April 2017
                2017
                : 17
                : 270
                Affiliations
                [1 ]GRID grid.17091.3e, , Department of Surgery, St. Paul’s Hospital, & University of British Columbia, ; C303 – 1081 Burrard Street, Vancouver, BC V6Z 1Y6 Canada
                [2 ]GRID grid.61971.38, Faculty оf Health Sciences, , Simon Fraser University, ; Burnaby, BC Canada
                [3 ]GRID grid.416553.0, British Columbia Centre For Excellence In HIV/AIDS, Providence Health Care, , St. Paul’s Hospital, ; Vancouver, BC Canada
                [4 ]GRID grid.17091.3e, Faculty of Medicine, , University of British Columbia, ; Vancouver, Canada
                [5 ]GRID grid.248762.d, Population and Preventive Oncology, , British Columbia Cancer Agency, ; Vancouver, BC Canada
                Article
                3229
                10.1186/s12885-017-3229-1
                5391557
                28410587
                8094f5b3-855c-400d-bb98-ba60a6f68ee9
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 March 2016
                : 24 March 2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Oncology & Radiotherapy
                cancer,hiv,aids,epidemiology,haart,malignancy
                Oncology & Radiotherapy
                cancer, hiv, aids, epidemiology, haart, malignancy

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