Risk of AIDS-Defining Cancers Among HIV-1–Infected Patients in France Between 1992 and 2009: Results From the FHDH-ANRS CO4 Cohort

Hleyhel, Mira; Belot, Aurélien; Bouvier, Anne; Tattevin, Pierre; Pacanowski, Jérôme; Genet, Philippe; Castro, Nathalie De; Berger, Jean-Luc; Dupont, Caroline; Lavolé, A.; Pradier, Christian; Salmon, Dominique; Simon, Anne; Martinez, Valérie; Costagliola, Dominique; Grabar, Sophie

doi:10.1093/cid/cit497

Cited by 98 publications

(85 citation statements)

References 25 publications

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“…Evidence supports decreasing trends for lung cancer and Hodgkin lymphoma and an increasing trend for liver cancer, but results for anal cancer have been inconsistent; many nonsignificant trends for specific NADC have been observed, perhaps due to insufficient statistical power [11, 16–19, 21–23, 26]. The ADC adjusted IR has continued to decline during the ART era [9, 11, 17, 18, 20, 23, 24]. …”

Section: Introductionmentioning

confidence: 99%

“…Despite the continued decline of the ADC IR, the relative risk (HIV+ versus uninfected) remains elevated, even in the more recent ART era [9, 11, 23]. The relative risk for NADC (grouped) [11, 12, 20, 23] and for specific NADC, including oral cavity and pharynx, anal, lung, and liver cancers and Hodgkin lymphoma, is elevated as well [27–29].…”

Section: Introductionmentioning

confidence: 99%

“…The relative risk for NADC (grouped) [11, 12, 20, 23] and for specific NADC, including oral cavity and pharynx, anal, lung, and liver cancers and Hodgkin lymphoma, is elevated as well [27–29]. However, few studies have examined time trends in cancer relative risk during the ART era [9, 16, 18, 19, 23]. Several of these studies compared HIV+ persons with the general population using standardized incidence ratios [18, 19], but we are aware of only one study (from Kaiser Permanente in California during 1996–2007) that examined cancer incidence rate ratio (IRR) time trends in HIV+ versus demographically-similar uninfected persons across a range of cancer groupings and specific types [23].…”

Section: Introductionmentioning

confidence: 99%

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Time trends in cancer incidence in persons living with HIV/AIDS in the antiretroviral therapy era

Park

Tate

Sigel

et al. 2016

Aids

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Objective Utilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the antiretroviral therapy (ART) era. Design Prospective cohort study. Methods We followed 44,787 HIV+ and 96,852 demographically-matched uninfected persons during 1997–2012. We calculated age-, sex-, and race/ethnicity-standardized incidence rates (IR) and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with IR and IRR period trend p-values for cancer groupings and specific cancer types. Results We observed 3,714 incident cancer diagnoses in HIV+ and 5,760 in uninfected persons. The HIV+ all cancer crude IR increased between 1997–2000 and 2009–2012 (p-trend=0.0019). However, after standardization, we observed highly significant HIV+ IR declines for all cancer (25% decline; p-trend<0.0001), AIDS-defining cancers (ADC; 55% decline; p-trend<0.0001), non-AIDS-defining cancers (NADC; 15% decline; p-trend=0.0003), and non-virus-related NADC (20% decline; p-trend<0.0001); significant IRR declines for all cancer (from 2.0 to 1.6; p-trend<0.0001), ADC (from 19 to 5.5; p-trend<0.0001), and non-virus-related NADC (from 1.4 to 1.2; p-trend=0.049); and borderline significant IRR declines for NADC (from 1.6 to 1.4; p-trend=0.078) and virus-related NADC (from 4.9 to 3.5; p-trend=0.071). Conclusion Improved HIV care resulting in improved immune function most likely contributed to the HIV+ IR and the IRR declines. Further promotion of early and sustained ART, improved ART regimens, reduction of traditional cancer risk factor (e.g., smoking) prevalence, and evidence-based screening could contribute to future cancer incidence declines among HIV+ persons.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Time trends in cancer incidence in persons living with HIV/AIDS in the antiretroviral therapy era

Park

Tate

Sigel

et al. 2016

Aids

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“…Therefore, studies that review the prevalence of comorbid conditions in HIV-infected individuals are needed. Patients with advanced stages of HIV infection or AIDS, due to compromised immune system, are at a high risk for developing AIDS-defining cancers or malignancies, such as Kaposi's sarcoma, non-Hodgkin lymphoma and cervical cancer (Chokunonga, Borok, Chirenje, Nyakabau, & Parkin, 2013;Hleyhel et al, 2013;Hymes et al, 1981). A continued high risk of non-AIDS-defining malignancies in the ART era is, however, an important concern (Silverberg & Abrams, 2009).…”

Section: Introductionmentioning

confidence: 99%

Prevalence, incidence, mortality and co-morbidities amongst human immunodeficiency virus (HIV) patients in Stockholm County, Sweden – The Greater Stockholm HIV Cohort Study

Jallow¹,

Ljunggren

Wändell

et al. 2014

AIDS Care

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Our aim was to study the prevalence and incidence of patients with human immunodeficiency virus (HIV) in the general population in Stockholm, Sweden. We also aimed to study mortality among individuals with HIV and to explore co-morbidities. The study population included all living persons who resided in Stockholm County, Sweden, as of 31 December 2012 (N = 2,212,435). Information on all consultations between 2007 and 2012 was obtained from primary health care, specialist outpatient care and inpatient care. Analyses were done by age and gender. All patients with a recorded diagnosis of HIV were included. The prevalence of HIV was calculated using 2012 data. The prevalence of HIV in Stockholm area as per end of December 2012 was as low as 0.1% in females and 0.2% in males, and the annual incidence of HIV continued to decline over the years. In recent years, cancers, diabetes and hypertension were about as common in individuals with HIV as in the general population. Males with HIV had 3- to 4-fold higher age-adjusted odds of being diagnosed with depression and 3-fold higher odds of anxiety disorders and women had 1.6 to 2-fold higher age-adjusted odds of depression and anxiety disorders, than males and females in the general population, respectively. The relatively good somatic health observed in this study could be attributed to nearly optimal HIV therapy in Sweden. The mental health of HIV patients was significantly worse than that in the general population and needs further attention.

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“…The introduction of combination antiretroviral therapy (cART) has drastically reduced the risk of non-Hodgkin lymphoma (NHL) and other AIDS-defining cancers; however, the risk of NHL in individuals with HIV remains ninefold higher than that in the general population (1). The mechanisms responsible for this increased risk have not been fully elucidated, but are thought to involve HIV-1-mediated impaired cellular immunity, loss of control over oncogenic viruses, and chronic B-cell activation.…”

mentioning

confidence: 99%

Expression of HIV-1 matrix protein p17 and association with B-cell lymphoma in HIV-1 transgenic mice

Carroll

Lafferty

Marchionni

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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HIV-1 infection is associated with increased risk for B-cell lymphomas. How HIV infection promotes the development of lymphoma is unclear, but it may involve chronic B-cell activation, inflammation, and/or impaired immunity, possibly leading to a loss of control of oncogenic viruses and reduced tumor immunosurveillance. We hypothesized that HIV structural proteins may contribute to lymphomagenesis directly, because they can persist long term in lymph nodes in the absence of viral replication. The HIV-1 transgenic mouse Tg26 carries a noninfectious HIV-1 provirus lacking part of the gag-pol region, thus constituting a model for studying the effects of viral products in pathogenesis. Approximately 15% of Tg26 mice spontaneously develop leukemia/lymphoma. We investigated which viral proteins are associated with the development of leukemia/lymphoma in the Tg26 mouse model, and performed microarray analysis on RNA from spleen and lymph nodes to identify potential mechanisms of lymphomagenesis. Of the viral proteins examined, only expression of HIV-1 matrix protein p17 was associated with leukemia/lymphoma development and was highly expressed in bone marrow before disease. The tumor cells resembled pro-B cells, and were CD19(+)IgM(-)IgD(-)CD93(+)CD43(+)CD21(-)CD23(-)VpreB(+)CXCR4(+) Consistent with the pro-B-cell stage of B-cell development, microarray analysis revealed enrichment of transcripts, including Rag1, Rag2, CD93, Vpreb1, Vpreb3, and Igll1 We confirmed RAG1 expression in Tg26 tumors, and hypothesized that HIV-1 matrix protein p17 may directly induce RAG1 in B cells. Stimulation of human activated B cells with p17 enhanced RAG1 expression in three of seven donors, suggesting that intracellular signaling by p17 may lead to genomic instability and transformation

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Risk of AIDS-Defining Cancers Among HIV-1–Infected Patients in France Between 1992 and 2009: Results From the FHDH-ANRS CO4 Cohort

Abstract: The incidence of all ADCs continued to fall, including cervical cancer, in the cART period, but the risk remained higher than in the general population in 2005-2009. In patients with stably restored immunity, KS remained significantly more frequent than in the general population.

Cited by 98 publications

References 25 publications

Time trends in cancer incidence in persons living with HIV/AIDS in the antiretroviral therapy era

Time trends in cancer incidence in persons living with HIV/AIDS in the antiretroviral therapy era

Prevalence, incidence, mortality and co-morbidities amongst human immunodeficiency virus (HIV) patients in Stockholm County, Sweden – The Greater Stockholm HIV Cohort Study

Expression of HIV-1 matrix protein p17 and association with B-cell lymphoma in HIV-1 transgenic mice

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