Despite advances in the treatment of HIV, HIV-infected people remain at increased risk for many cancers, and the number of non-AIDS-defining cancers is increasing with the aging of the HIV-infected ...population. No prior study has comprehensively evaluated the effect of HIV on cancer-specific mortality.
We identified cases of 14 common cancers occurring from 1996 to 2010 in six US states participating in a linkage of cancer and HIV/AIDS registries. We used Cox regression to examine the association between patient HIV status and death resulting from the presenting cancer (ascertained from death certificates), adjusting for age, sex, race/ethnicity, year of cancer diagnosis, and cancer stage. We included 1,816,461 patients with cancer, 6,459 (0.36%) of whom were HIV infected.
Cancer-specific mortality was significantly elevated in HIV-infected compared with HIV-uninfected patients for many cancers: colorectum (adjusted hazard ratio HR, 1.49; 95% CI, 1.21 to 1.84), pancreas (HR, 1.71; 95% CI, 1.35 to 2.18), larynx (HR, 1.62; 95% CI, 1.06 to 2.47), lung (HR, 1.28; 95% CI, 1.17 to 1.39), melanoma (HR, 1.72; 95% CI, 1.09 to 2.70), breast (HR, 2.61; 95% CI, 2.06 to 3.31), and prostate (HR, 1.57; 95% CI, 1.02 to 2.41). HIV was not associated with increased cancer-specific mortality for anal cancer, Hodgkin lymphoma, or diffuse large B-cell lymphoma. After further adjustment for cancer treatment, HIV remained associated with elevated cancer-specific mortality for common non-AIDS-defining cancers: colorectum (HR, 1.40; 95% CI, 1.09 to 1.80), lung (HR, 1.28; 95% CI, 1.14 to 1.44), melanoma (HR, 1.93; 95% CI, 1.14 to 3.27), and breast (HR, 2.64; 95% CI, 1.86 to 3.73).
HIV-infected patients with cancer experienced higher cancer-specific mortality than HIV-uninfected patients, independent of cancer stage or receipt of cancer treatment. The elevation in cancer-specific mortality among HIV-infected patients may be attributable to unmeasured stage or treatment differences as well as a direct relationship between immunosuppression and tumor progression.
Epstein-Barr virus (EBV), a ubiquitous herpes virus that infects 90% of humans by adulthood, is linked to the development of various cancers, including nasopharyngeal carcinoma, gastric cancer, ...Burkitt lymphoma, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma. We reviewed the literature published since 1980 regarding an association between antibodies against EBV proteins and the risk of EBV-associated malignancies. Immunoglobulin A antibody levels that are elevated before diagnosis have consistently been associated with the risk of nasopharyngeal carcinoma, and patients with Hodgkin lymphoma have significantly higher immunoglobulin G antibody levels than disease-free controls. However, the link between the immune response to EBV and other EBV-associated malignancies was less clear. Although evidence of an association between the risk of Burkitt lymphoma and immunoglobulin G antibodies was consistent for available studies, the sample sizes were limited. Evidence for a link between antibodies against EBV and risk of either gastric cancer or NHL was inconsistent. Future investigations should account for tumor EBV status because only 7%-10% of gastric tumors and select NHL subtypes are related to EBV infection. Comparing differences in the associations between the humoral immune response to EBV and disease risk across cancers may help elucidate how this ubiquitous virus contributes to distinct tumors globally.
CD19 CAR T-cell therapy with axicabtagene ciloleucel (axi-cel) for relapsed or refractory (R/R) large B cell lymphoma (LBCL) may lead to durable remissions, however, prolonged cytopenias and ...infections may occur. In this single center retrospective study of 85 patients, we characterized immune reconstitution and infections for patients remaining in remission after axi-cel for LBCL. Prolonged cytopenias (those occurring at or after day 30 following infusion) were common with >= grade 3 neutropenia seen in 21/70 (30-0%) patients at day 30 and persisting in 3/31 (9-7%) patients at 1 year. B cells were undetectable in 30/34 (88-2%) patients at day 30, but were detected in 11/19 (57-9%) at 1 year. Median IgG levels reached a nadir at day 180. By contrast, CD4 T cells decreased from baseline and were persistently low with a median CD4 count of 155 cells/μl at 1 year after axi-cel (n=19, range 33 - 269). In total, 23/85 (27-1%) patients received IVIG after axi-cel, and 34/85 (40-0%) received G-CSF. Infections in the first 30 days occurred in 31/85 (36-5%) patients, of which 11/85 (12-9%) required intravenous antibiotics or hospitalization ("severe") and were associated with cytokine release syndrome (CRS), neurotoxicity, tocilizumab use, corticosteroid use, and bridging therapy on univariate analyses. After day 30, 7 severe infections occurred, with no late deaths due to infection. Prolonged cytopenias are common following axi-cel therapy for LBCL and typically recover with time. Most patients experience profound and prolonged CD4 T cell immunosuppression without severe infection.
Background
Transplant recipients have an elevated risk of cancer because of immunosuppressive medications used to prevent organ rejection, but to the authors’ knowledge no study to date has ...comprehensively examined associations between transplantation status and mortality after a cancer diagnosis.
Methods
The authors assessed cases in the US general population (N=7,147,476) for 16 different cancer types as ascertained from 11 cancer registries. The presence of a solid organ transplant prior to diagnosis (N=11,416 cancer cases) was identified through linkage with the national transplantation registry (1987‐2014). Cox models were used to examine the association between transplantation status and cancer‐specific mortality, adjusting for demographic characteristics and cancer stage.
Results
For the majority of cancers, cancer‐specific mortality was higher in transplant recipients compared with other patients with cancer. The increase was particularly pronounced for melanoma (adjusted hazard ratio aHR, 2.59; 95% confidence interval 95% CI, 2.18‐3.00) and cancers of the breast (aHR, 1.88; 95% CI, 1.61‐2.19), bladder (aHR, 1.85; 95% CI, 1.58‐2.17), and colorectum (aHR, 1.77; 95% CI, 1.60‐1.96), but it also was increased for cancers of the oral cavity/pharynx, stomach, pancreas, kidney, and lung as well as diffuse large B‐cell lymphoma (aHR range, 1.21‐1.47). Associations remained significant after adjustment for first‐course cancer treatment and generally were stronger among patients with local‐stage cancers for whom potentially curative treatment was provided, including patients with melanoma (aHR, 3.82; 95% CI, 2.94‐4.97) and cancers of the colorectum (aHR, 2.77; 95% CI, 2.07‐3.70), breast (aHR, 2.08; 95% CI, 1.50‐2.88), and prostate (aHR, 1.60; 95% CI, 1.12‐2.29), despite the lack of an association for prostate cancer overall.
Conclusions
For multiple cancer types, transplant recipients with cancer appear to have an elevated risk of dying of their cancer, even after adjustment for stage and treatment, which may be due to impaired immunity.
The number of solid organ transplant recipients has increased within the last 10 years, with nearly 35,000 transplantations reported to have occurred in the United States in 2017. Although solid organ transplantation is life‐saving, recipients have an elevated risk of many types of cancer, and for multiple cancer types, transplant recipients with cancer appear to have an elevated risk of dying of their cancer, even after adjustment for stage of disease and treatment, which may be due to impaired immunity.
Background
People living with HIV (PLWH) are at an increased risk of developing several cancers, but to the authors’ knowledge less is known regarding how HIV impacts the rate of progression to ...advanced cancer or death.
Methods
The authors compared stage of disease at the time of presentation and mortality after diagnosis between 14,453 PLWH and 6,368,126 HIV‐uninfected patients diagnosed with cancers of the oral cavity, stomach, colorectum, anus, liver, pancreas, lung, female breast, cervix, prostate, bladder, kidney, and thyroid and melanoma using data from the National Cancer Data Base (2004‐2014). Polytomous logistic regression and Cox proportional hazards regression were used to evaluate the association between HIV, cancer stage, and stage‐adjusted mortality after diagnosis, respectively. Regression models accounted for the type of health facility at which cancer treatment was administered and the type of individual health insurance.
Results
HIV‐infected patients with cancer were found to be more likely to be uninsured (HIV‐infected: 5.0% vs HIV‐uninfected: 3.3%; P < .0001) and were less likely to have private health insurance (25.4% vs 44.7%; P < .0001). Compared with those not infected with HIV, the odds of being diagnosed at an advanced stage of disease were significantly elevated in PLWH for melanoma and cancers of the oral cavity, liver, female breast, prostate, and thyroid (odds ratio for stage IV vs stage I range, 1.24‐2.06). PLWH who were diagnosed with stage I to stage III disease experienced elevated mortality after diagnosis across 13 of the 14 cancer sites evaluated, with hazard ratios ranging from 1.20 (95% CI, 1.14‐1.26) for lung cancer to 1.85 (95% CI, 1.68‐2.04), 1.85 (95% CI, 1.51‐2.27), and 2.93 (95% CI, 2.08‐4.13), respectively, for cancers of the female breast, cervix, and thyroid.
Conclusions
PLWH were more likely to be diagnosed with advanced‐stage cancers and to experience elevated mortality after a cancer diagnosis, even after accounting for health care–related factors.
Individuals living with HIV are more likely to be diagnosed with advanced‐stage cancers and to experience elevated mortality after their cancer diagnosis, even after accounting for health care–related factors. In the current study, the authors compare stage of disease at the time of presentation and mortality after diagnosis between 14,453 individuals infected with HIV and 6,368,126 HIV‐uninfected patients diagnosed with cancers of the oral cavity, stomach, colorectum, anus, liver, pancreas, lung, female breast, cervix, prostate, bladder, kidney, and thyroid and melanoma using data from the National Cancer Data Base.
Although people living with HIV or AIDS (PLWHA) are at higher risk for many cancers, breast, prostate, and colorectal cancer rates are lower in this patient population. Because these tumors are often ...screen-detected, these inverse associations could be driven by HIV-related differences in utilization of cancer screening.
We ascertained incident breast, prostate, and colorectal cancer in PLWHA using data from the HIV/AIDS Cancer Match Study (1996-2012). Comparisons with general population cancer rates were made using standardized incidence ratios (SIRs), overall and stratified by tumor stage/size, breast cancer estrogen receptor status, and colorectal site. We also examined the potential effect of study design and unmeasured confounding on inverse standardized incidence ratios.
Compared with the general population, PLWHA had lower rates of invasive breast (SIR = 0.63, 95% confidence interval CI = 0.58 to 0.68), prostate (SIR = 0.48, 95% CI = 0.46 to 0.51), proximal colon (SIR = 0.67, 95% CI = 0.59 to 0.75), distal colon (SIR = 0.51, 95% CI = 0.43 to 0.59), and rectal cancers (SIR = 0.69, 95% CI = 0.61 to 0.77). Reduced risk persisted across tumor stage/size for prostate and colorectal cancers. Although distant-stage breast cancer rates were not reduced (SIR = 0.94, 95% CI = 0.73 to 1.20), HIV-infected women had lower rates of large (>5 cm) breast tumors (SIR = 0.65, 95% CI = 0.50 to 0.83). The magnitude of these inverse standardized incidence ratios could not plausibly be attributed to case underascertainment, out-migration, or unmeasured confounding.
Breast, prostate, and colorectal cancer rates are markedly lower among PLWHA, including rates of distant-stage/large tumors that are not generally screen-detected. This set of inverse HIV-cancer associations is therefore unlikely to be due primarily to differential screening and may instead represent biological relationships requiring future investigation.
Human immunodefieciency virus (HIV)-infected persons are living longer in the era of effective HIV treatment, resulting in an increasing cancer burden in this population. The combined effects of HIV ...and cancer on mortality are incompletely understood.
We examined whether individuals with both HIV and cancer have excess mortality using data from the HIV/AIDS Cancer Match Study and the National Center for Health Statistics (1996-2010). We compared age, sex, and race-stratified mortality between people with and without HIV or one of the following cancers: lung, breast, prostate, colorectum, anus, Hodgkin lymphoma, or non-Hodgkin lymphoma. We utilized additive Poisson regression models that included terms for HIV, cancer, and an interaction for their combined effect on mortality. We report the number of excess deaths per 1,000 person-years for models with a significant interaction (
< 0.05).
For all cancers examined except prostate cancer, at least one demographic subgroup of HIV-infected cancer patients experienced significant excess mortality. Excess mortality was most pronounced at younger ages (30-49 years), with large excesses for males with lung cancer (white race: 573 per 1,000 person-years; non-white: 503) and non-Hodgkin lymphoma (white: 236; non-white: 261), and for females with Hodgkin lymphoma (white: 216; non-white: 136) and breast cancer (non-white: 107).
In the era of effective HIV treatment, overall mortality in patients with both HIV and cancer was significantly higher than expected on the basis of mortality rates for each disease separately.
These results suggest that HIV may contribute to cancer progression and highlight the importance of improved cancer prevention and care for the U.S. HIV population.
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Cancer risk in 183542 older persons living with human immunodeficiency virus infection was evaluated using data from the HIV/AIDS Cancer Match Study. Relative risk of most cancers decreased with age, ...but absolute risks were higher for some cancers.
Abstract
Background
Cancer risk is increased in persons living with human immunodeficiency virus (HIV) (PLWH). Improved survival has led to an aging of PLWH. We evaluated the cancer risk in older PLWH (age ≥50 years).
Methods
We included data from the HIV/AIDS Cancer Match Study (1996-2012) and evaluated risks of Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, and cervical, anal, lung, liver, oral cavity/pharyngeal, breast, prostate, and colon cancers in older PLWH with risk in the general population by calculating standardized incidence ratios (SIRs) and excess absolute risks (EARs). Cancer risk by time since HIV diagnosis was estimated using Poisson regression.
Results
We identified 10371 cancers among 183542 older PLWH. Risk was significantly increased for KS (SIR, 103.34), NHL (3.05), Hodgkin lymphoma (7.61), and cervical (2.02), anal (14.00), lung (1.71), liver (2.91), and oral cavity/pharyngeal (1.66) cancers, and reduced for breast (0.61), prostate (0.47), and colon (0.63) cancers. SIRs declined with age for all cancers; however, EARs increased with age for anal, lung, liver, and oral cavity/pharyngeal cancers. Cancer risk was highest for most cancers within 5 years after HIV diagnosis; risk decreased with increasing time since HIV diagnosis for KS, NHL, lung cancer, and Hodgkin lymphoma.
Conclusions
Cancer risk is elevated among older PLWH. Although SIRs decrease with age, EARs are higher for some cancers, reflecting a greater absolute excess in cancer incidence among older PLWH. High risk in the first 5 years after HIV diagnosis for some cancers highlights the need for early HIV diagnosis and rapid treatment initiation.
Although anal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are generally combined in cancer surveillance, their etiologies likely differ. Here, we describe demographic characteristics and ...trends in incidence rates (IR) of anal cancer by histology (SCC, ADC) and behavior (invasive, in situ) in the United States.
With data from the Surveillance, Epidemiology, and End Results (SEER) Program, we estimated age-adjusted anal cancer IRs across behavior/histology by demographic and tumor characteristics for 2000-2011. Trends in IRs and annual percent changes during 1977-2011 were also estimated and compared with rectal cancer.
Women had higher rates of SCC rate ratio (RR), 1.45; 95% confidence interval (CI), 1.40-1.50 and lower rates of ADC (RR, 0.68; 95% CI, 0.62-0.74) and squamous carcinoma in situ (CIS; RR, 0.36; 95% CI, 0.34-0.38) than men. Blacks had lower rates of SCC (RR, 0.82; 95% CI, 0.77-0.87) and CIS (RR, 0.90; 95% CI, 0.83-0.98) than non-Hispanic whites, but higher rates of ADC (RR, 1.48; 95% CI, 1.29-1.70). Anal cancer IRs were higher in men and blacks aged <40 years. During 1992-2011, SCC IRs increased 2.9%/year, ADC IRs declined nonsignificantly, and CIS IRs increased 14.2%/year. SCC and ADC IR patterns and trends were similar across anal and rectal cancers.
Rates of anal SCC and CIS have increased strongly over time, in contrast to rates of anal ADC, similar to trends observed for rectal SCC and ADC.
Anal SCC and ADC likely have different etiologies, but may have similar etiologies to rectal SCC and ADC, respectively. Strong increases in CIS IRs over time may reflect anal cancer screening patterns.
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