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Among patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non-Hodgkin’s lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin’s lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin’s lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention.

Solid organ transplant recipients, who are medically immunosuppressed to prevent graft rejection, have increased melanoma risk, but risk factors and outcomes are incompletely documented. We evaluated melanoma incidence among 139,991 non-Hispanic white transplants using linked US transplant-cancer registry data (1987–2010). We used standardized incidence ratios (SIRs) to compare incidence with the general population and incidence rate ratios (IRRs) from multivariable Poisson models to assess risk factors. Separately, we compared post-melanoma survival among transplant recipients (n=182) and non-recipients (n=131,358) using multivariable Cox models. Among transplant recipients, risk of invasive melanoma (n=519) was elevated (SIR=2.20, 95% CI 2.01–2.39), especially for regional stage tumors (SIR=4.11, 95% CI 3.27–5.09). Risk of localized tumors was stable over time after transplantation but higher with azathioprine maintenance therapy (IRR=1.35, 95% CI 1.03–1.77). Risk of regional/distant stage tumors peaked within 4 years following transplantation and increased with polyclonal antibody induction therapy (IRR=1.65, 95% CI 1.02–2.67). Melanoma-specific mortality was higher among transplant recipients than non-recipients (hazard ratio 2.98, 95% CI 2.26–3.93). Melanoma exhibits increased incidence and aggressive behavior under transplant-related immunosuppression. Some localized melanomas may result from azathioprine, which acts synergistically with UV radiation, whereas T-cell–depleting induction therapies may promote late-stage tumors. Our findings support sun safety practices and skin screening for transplant recipients.

Screening for oral leukoplakia, an oral cavity cancer (OCC) precursor, could lead to earlier detection of OCC. However, the progression rate from leukoplakia to OCC and the benefits of leukoplakia screening for improving OCC outcomes are currently unclear. We conducted a case–cohort study of U.S. adults ages ≥65 years in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage. We identified leukoplakia diagnoses through Medicare claims, and OCC diagnoses through SEER cancer registries. Weighted Cox regression was used to estimate leukoplakia associations with OCC incidence, and the absolute OCC risk following leukoplakia diagnosis was calculated. Among OCC cases, we compared OCC stage and OCC survival between cases with a prior leukoplakia diagnosis versus those without prior leukoplakia. Among 470,266 individuals in the SEER-Medicare subcohort, 1,526 (0.3%) had a leukoplakia diagnosis. Among people with leukoplakia, the cumulative OCC incidence was 0.7% at 3 months and 2.5% at 5 years. OCC risk was most increased

Sirolimus, an immunosuppressant option for kidney transplant recipients, may reduce cancer risk by interrupting the mammalian target of rapamycin pathway. However, studies of sirolimus and cancer incidence in kidney recipients have not been definitive, and have had limited ability to examine specific cancer types. The literature was systematically reviewed to identify randomized controlled trials (RCTs) and observational studies of kidney recipients that compared sirolimus users to sirolimus nonusers. Meta-analytic methods were used to obtain pooled estimates of the association between sirolimus use and incidence of total cancer and specific cancer types. Estimates were stratified by study type (RCT vs. observational) and use of cyclosporine (an immunosuppressant that affects DNA repair). Twenty RCTs and two observational studies were eligible for meta-analysis, including 39,039 kidney recipients overall. Sirolimus use was associated with lower overall cancer incidence (incidence rate ratio [IRR] = 0.71, 95% CI = 0.56–0.90), driven by a reduction in incidence of nonmelanoma skin cancer (NMSC, IRR = 0.49, 95% CI = 0.32–0.76). The protective effect of sirolimus on NMSC risk was most notable in studies comparing sirolimus against cyclosporine (IRR = 0.19, 95% CI = 0.04–0.84). After excluding NMSCs, there was no overall association between sirolimus and incidence of other cancers (IRR = 1.06, 95% CI = 0.69–1.63). However, sirolimus use had associations with lower kidney cancer incidence (IRR = 0.40, 95% CI = 0.20–0.81), and higher prostate cancer incidence (IRR = 1.85, 95% CI = 1.17–2.91). Among kidney recipients, sirolimus users have lower NMSC risk, which may be partly due to removal of cyclosporine. Sirolimus may also reduce kidney cancer risk but did not appear protective for other cancers, and it may actually increase prostate cancer risk.

Sirolimus has anti-carcinogenic properties and can be included in maintenance immunosuppressive therapy following kidney transplantation. We investigated sirolimus effects on cancer incidence among kidney recipients. The US transplant registry was linked with 15 population-based cancer registries and national pharmacy claims. Recipients contributed sirolimus-exposed time when sirolimus claims were filled, and unexposed time when other immunosuppressant claims were filled without sirolimus. Cox regression was used to estimate associations with overall and specific cancer incidence, excluding nonmelanoma skin cancers (not captured in cancer registries). We included 32,604 kidney transplants (5687 sirolimus-exposed). Overall, cancer incidence was suggestively lower during sirolimus use (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.70-1.11). Prostate cancer incidence was higher during sirolimus use (HR = 1.86, 95% CI = 1.15-3.02). Incidence of other cancers was similar or lower with sirolimus use, with a 26% decrease overall (HR = 0.74, 95% CI = 0.57-0.96, excluding prostate cancer). Results were similar after adjustment for demographic and clinical characteristics. This modest association does not provide strong evidence that sirolimus prevents posttransplant cancer, but it may be advantageous among kidney recipients with high cancer risk. Increased prostate cancer diagnoses may result from sirolimus effects on screen detection.

Background: Elevated keratinocyte carcinoma risk is present with several immune-related conditions, e.g., solid organ transplantation and non-Hodgkin lymphoma. Because many immune-related conditions are rare, their relationships with keratinocyte carcinoma have not been studied. Methods: We used Medicare claims to identify cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) cases in 2012, and controls matched on sex and age. All subjects were aged 65 to 95 years, of white race, and had attended ≥1 dermatologist visit in 2010–2011. Immune-related conditions were identified during 1999–2011 using Medicare claims. Associations were estimated with logistic regression, with statistical significance determined after Bonferroni correction for multiple comparisons. Results: We included 258,683 SCC and 304,903 BCC cases. Of 47 immune-related conditions, 21 and 9 were associated with increased SCC and BCC risk, respectively. We identified strongly elevated keratinocyte carcinoma risk with solid organ transplantation (SCC OR = 5.35; BCC OR = 1.94) and non-Hodgkin lymphoma (SCC OR = 1.62; BCC OR = 1.25). We identified associations with common conditions, e.g., rheumatoid arthritis [SCC OR = 1.06, 95% confidence interval (95% CI), 1.04–1.09] and Crohn's disease (SCC OR = 1.33, 95% CI, 1.27–1.39; BCC OR = 1.10, 95% CI, 1.05–1.15), and rare or poorly characterized conditions, e.g., granulomatosis with polyangiitis (SCC OR = 1.88; 95% CI, 1.61–2.19), autoimmune hepatitis (SCC OR = 1.81; 95% CI, 1.52–2.16), and deficiency of humoral immunity (SCC OR = 1.51, 95% CI, 1.41–1.61; BCC OR = 1.22, 95% CI, 1.14–1.31). Most conditions were more positively associated with SCC than BCC. Associations were generally consistent regardless of prior keratinocyte carcinoma history. Conclusions: Many immune-related conditions are associated with elevated keratinocyte carcinoma risk and appear more tightly linked to SCC. Impact: Immunosuppression or immunosuppressive treatment may increase keratinocyte carcinoma risk, particularly SCC. Cancer Epidemiol Biomarkers Prev; 26(7); 998–1007. ©2017 AACR.

Importance The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti–PD-1 and anti–PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients. Objective To compare the local tumor immune microenvironment (TME) in anal SCCs from HIV-positive and HIV-negative patients. Design, Setting, and Participants Anal SCC tumor specimens derived from the AIDS and Cancer Specimen Resource (National Cancer Institute) and Johns Hopkins Hospital included specimens. Tumors were subjected to immunohistochemical analysis for immune checkpoints (PD-L1, PD-1, LAG-3) and immune cell (IC) subsets (CD3, CD4, CD8, CD68). Expression profiling for immune-related genes was performed on select HIV-positive and HIV-negative cases in PD-L1 + tumor areas associated with ICs. Main Outcomes and Measures Programmed death-ligand 1 expression on tumor cells and ICs, PD-L1 patterns (adaptive vs constitutive), degree of IC infiltration, quantified densities of IC subsets, and gene expression profiles in anal SCCs from HIV-positive vs HIV-negative patients. Results Approximately half of 40 tumor specimens from 23 HIV-positive and 17 HIV-negative patients (29 men and 11 women; mean [SD] age, 51 [9.9] years) demonstrated tumor cell PD-L1 expression, regardless of HIV status. Median IC densities were not significantly decreased in HIV-associated tumors for any cellular subset studied. Both adaptive (IC-associated) and constitutive PD-L1 expression patterns were observed. Immune cell PD-L1 expression correlated with increasing intensity of IC infiltration ( r = 0.52; 95% CI, 0.26-0.78; P + T-cell density ( r = 0.35; 95% CI, 0.11-0.59; P = .03). Gene expression profiling revealed comparable levels of IFNG in the TME of both HIV-positive and HIV-negative patients. A significant increase in IL18 expression levels was observed in HIV-associated anal SCCs (fold change, 12.69; P Conclusions and Relevance HIV status does not correlate with the degree or composition of IC infiltration or PD-L1 expression in anal SCC. These findings demonstrate an immune-reactive TME in anal SCCs from HIV-positive patients and support clinical investigations of PD-1/PD-L1 checkpoint blockade in anal SCC, irrespective of patient HIV status.

Background In a European cohort, it was previously reported that 35% of oropharyngeal cancer (OPC) patients were human papillomavirus type-16 (HPV16) seropositive up to 10 years before diagnosis vs 0.6% of cancer-free controls. Here, we describe the kinetics of HPV16-E6 antibodies prior to OPC diagnosis. Methods We used annual serial prediagnostic blood samples from the PLCO Cancer Screening Trial. Antibodies to HPV were initially assessed in prediagnostic blood drawn at study enrollment from 198 incident head and neck cancer patients (median years to cancer diagnosis = 6.6) and 924 matched control subjects using multiplex serology, and subsequently in serial samples (median = 5/individual). Available tumor samples were identified and tested for HPV16 RNA to define HPV-driven OPC. Results HPV16-E6 antibodies were present at baseline in 42.3% of 52 OPC patients and 0.5% of 924 control subjects. HPV16-E6 antibody levels were highly elevated and stable across serial blood samples for 21 OPC patients who were seropositive at baseline, as well as for one OPC patient who seroconverted closer to diagnosis. All five subjects with HPV16-driven OPC tumors were HPV16-E6-seropositive, and the four subjects with HPV16-negative OPC tumors were seronegative. The estimated 10-year cumulative risk of OPC was 6.2% (95% confidence interval [CI] = 1.8% to 21.5%) for HPV16-E6-seropositive men, 1.3% (95% CI = 0.1% to 15.3%) for HPV16-E6-seropositive women, and 0.04% (95% CI = 0.03% to 0.06%) among HPV16-E6-seronegative individuals. Conclusions Forty-two percent of subjects diagnosed with OPC between 1994 and 2009 in a US cohort were HPV16-E6 seropositive, with stable antibody levels during annual follow-up for up to 13 years prior to diagnosis. Tumor analysis indicated that the sensitivity and specificity of HPV16-E6 antibodies were exceptionally high in predicting HPV-driven OPC.

Background Cancer remains an important cause of morbidity and mortality in people with human immunodeficiency virus (PWHIV) on effective antiretroviral therapy (ART). Estimates of cancer-attributable mortality can inform public health efforts. Methods We evaluated 46956 PWHIV receiving ART in North American HIV cohorts (1995-2009). Using information on incident cancers and deaths, we calculated population-attributable fractions (PAFs), estimating the proportion of deaths due to cancer. Calculations were based on proportional hazards models adjusted for age, sex, race, HIV risk group, calendar year, cohort, CD4 count, and viral load. Results There were 1997 incident cancers and 8956 deaths during 267145 person-years of follow-up, and 11.9% of decedents had a prior cancer. An estimated 9.8% of deaths were attributable to cancer (cancer-attributable mortality rate 327 per 100000 person-years). PAFs were 2.6% for AIDS-defining cancers (ADCs, including non-Hodgkin lymphoma, 2.0% of deaths) and 7.1% for non-AIDS-defining cancers (NADCs: lung cancer, 2.3%; liver cancer, 0.9%). PAFs for NADCs were higher in males and increased strongly with age, reaching 12.5% in PWHIV aged 55+ years. Mortality rates attributable to ADCs and NADCs were highest for PWHIV with CD4 counts

BACKGROUND CONTEXT There continues to be uncertainty in the appropriate treatment approach for adult symptomatic lumbar scoliosis (ASLS). Nonoperative care has not been shown to improve outcomes. Surgical treatment has been shown to improve outcomes, but is costly with high revision rates. PURPOSE To perform an intent-to-treat cost-effectiveness study comparing operative vs nonoperative care for ASLS. STUDY DESIGN/SETTING Secondary analysis using data from the NIH sponsored study on ASLS that included randomized and observational arms. PATIENT SAMPLE Patients with at least five-year follow-up data were included. OUTCOME MEASURES SRS-22R, Oswestry Disability Index, Short Form-12. METHODS Patients with at least five-year follow-up data were included. Data collected every three months included use of nonoperative modalities, medications and employment status. Costs for index and revision surgeries and nonoperative modalities were determined using Medicare allowable rates. Medication costs were determined using the RedBook and indirect costs were calculated based on reported employment status and income. Quality adjusted life years (QALY) were determined using the SF6D. RESULTS There were 81 of 95 cases in the operative (Op) and 81 of 95 in the nonoperative (NonOp) group with complete five-year follow-up data. Not all patients were eligible for five-year follow-up at the time of the analysis. All patients in the Op and 24 (30%) in the NonOp group had surgery by five years. At five years, the cumulative cost for Op was $96,000 with a QALY gain of 2.44 and for NonOp the cumulative cost was $49,546 with a QALY gain of 0.75 with an ICER of $27,480 per QALY gain. CONCLUSIONS In an intent-to treat analysis, neither treatment was dominant, as the greater gains in QALY in the surgery group come at a greater cost. The ICER for operative compared to nonoperative treatment was above the threshold generally considered cost-effective in the first three years of the study but improved over time and was highly cost-effective at four and five years. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT Adult symptomatic lumbar Scoliosis (ASLS) has become increasingly prevalent as the population ages. ASLS can be accompanied by neurogenic claudication, leading to difficulty walking. Functional treadmill testing (FTT) has been previously described as an objective tool to evaluate patients suffering from neurogenic claudication. FTT may provide an objective tool to evaluate patients with ASLS and identify patients who may benefit from surgical treatment. PURPOSE To determine if FTT demonstrates objective significant differences between patients treated surgically and nonsurgically for ASLS. STUDY DESIGN/SETTING Secondary analysis using data from the NIH sponsored study on ASLS that included randomized and observational arms. PATIENT SAMPLE Patients enrolled in the NIH sponsored study on ASLS. OUTCOME MEASURES Functional treadmill test, back and leg pain scores METHODS One hundred and eighty-seven patients who underwent nonsurgical (n=88) or surgical treatment (n=99) of ASLS with complete baseline and two-year post-treatment FTTs were identified. FTT parameters included maximum speed, time to onset of symptoms, distance ambulated, time ambulated, and the difference in back and leg pain before and after testing. RESULTS At baseline, patients treated operatively reported an onset of symptoms on FTT significantly sooner than those treated nonoperatively (5.5min vs 7.7min, p=0.025). When compared to baseline, operatively treated patients experienced significant improvement at 2 years in time ambulated (26.5min vs 24.4 min, p=0.001). Additionally, in the operative group, the post-treadmill minus pre-treadmill BP scores (0.5 vs 1.6 p=0.001) and the post-treadmill minus pre-treadmill leg pain scores (0.4 vs 1.4, p CONCLUSIONS FTT is a useful adjunct to assess treatment outcomes in patients with ASLS. FTT results were different at baseline between patients treated operatively and nonoperatively. Patients who had surgery had improvements in their post-treadmill minus pre-treadmill back and leg pain scores at two year follow-up. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

OBJECTIVE To examine the association between early HIV viremia and mortality after HIV-associated lymphoma. DESIGN Multicenter observational cohort study. SETTING Center for AIDS Research Network of Integrated Clinical Systems cohort. PARTICIPANTS HIV-infected patients with lymphoma diagnosed between 1996 and 2011, who were alive 6 months after lymphoma diagnosis and with at least two HIV RNA values during the 6 months after lymphoma diagnosis. EXPOSURE Cumulative HIV viremia during the 6 months after lymphoma diagnosis, expressed as viremia copy-6-months. MAIN OUTCOME MEASURE All-cause mortality between 6 months and 5 years after lymphoma diagnosis. RESULTS Of 224 included patients, 183 (82%) had non-Hodgkin lymphoma (NHL) and 41 (18%) had Hodgkin lymphoma. At lymphoma diagnosis, 105 (47%) patients were on antiretroviral therapy (ART), median CD4⁺ cell count was 148 cells/μl (interquartile range 54-322), and 33% had suppressed HIV RNA (

OBJECTIVE Laboratory monitoring is recommended during combination antiretroviral therapy (cART), but the pattern of detected abnormalities and optimal monitoring are unknown. We assessed laboratory abnormalities during initial cART in 2000-2010 across the United States. DESIGN Observational study in the Centers for AIDS Research Network of Integrated Clinical Systems Cohort. METHODS Among patients with normal results within a year prior to cART initiation, time to first significant abnormality was assessed by Kaplan-Meier curves stratified by event type, with censoring at first of regimen change, loss to follow-up, or 104 weeks. Incidence rates of first events were estimated using Poisson regression; multivariable analyses identified associated factors. Results were stratified by time (16 weeks) from therapy initiation. RESULTS A total of 3470 individuals contributed 3639 person-years. Median age, pre-cART CD4, and follow-up duration were 40 years, 206 cells/μl, and 51 weeks, respectively. Incidence rates for significant abnormalities (per 100 person-years) in the first 16 weeks post-cART initiation were as follows: lipid=49 [95% confidence interval (CI) 41-58]; hematologic=44 (40-49); hepatic=24 (20-27); and renal=9 (7-11), dropping substantially during weeks 17-104 of cART to lipid=23 (18-29); hematologic=5 (4-6); hepatic=6 (5-8); and renal=2 (1-3) (all P

Background: Recombinant bone morphogenetic proteins (BMPs) are growth factors utilized in lumbar arthrodeses. Limited data from randomized trials suggest that BMP may increase cancer risk. We sought to evaluate cancer risk and mortality following the use of BMP in lumbar arthrodesis. Methods: Within the linked Surveillance, Epidemiology, and End Results (SEER) Program-Medicare cohort, we conducted a case-cohort study of 7,278 individuals who were ≥65 years of age and had undergone a lumbar arthrodesis from 2004 to 2011. Of these patients, 3,627 were individuals in a 5% random subcohort of Medicare enrollees in SEER areas including 191 who developed cancer, and there were 3,651 individuals outside the subcohort who developed cancer. Weighted Cox proportional-hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cancer on the basis of exposure to BMP. Results: In the SEER-Medicare subcohort, 30.7% of individuals who underwent a lumbar arthrodesis received BMP. BMP was not associated with overall cancer risk in univariate analyses (HR, 0.92 [95% CI, 0.82 to 1.02]) or after adjustment for demographic characteristics, comorbidities, hospital size, history of cancer, and calendar year (adjusted HR, 0.94 [95% CI, 0.84 to 1.05]). Individual cancer types were also not significantly elevated (p > 0.05 for all) in BMP users compared with nonusers. In addition, BMP use was not associated with a new cancer in people who had cancer prior to undergoing lumbar arthrodesis (adjusted HR, 1.04 [95% CI, 0.71 to 1.52]) or with mortality after a cancer diagnosis (adjusted HR, 1.05 [95% CI, 0.93 to 1.19]). Conclusions: In a large population of elderly U.S. adults undergoing lumbar arthrodesis, BMP use was not associated with cancer risk or mortality. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

BACKGROUND: Previous studies demonstrated increased digestive tract cancers among individuals with cystic fibrosis (CF), particularly among lung transplant recipients. We describe cancer incidence among CF and non-CF lung recipients. METHODS: We used data from the US transplant registry and 16 cancer registries. Standardized incidence ratios (SIRs) compared cancer incidence to the general population, and competing risk methods were used for the cumulative incidence of colorectal cancer. RESULTS: We evaluated 10,179 lung recipients (1,681 with CF). Risk was more strongly increased in CF recipients than non-CF recipients for overall cancer (SIR 9.9 vs. 2.7) and multiple cancers including colorectal cancer (24.2 vs. 1.7), esophageal cancer (56.3 vs. 1.3), and non-Hodgkin lymphoma (61.8 vs. 9.4). At five years post-transplant, colorectal cancer was diagnosed in 0.3% of CF recipients aged

Background: Certain medical conditions affect risk of non-Hodgkin lymphoma (NHL), but the full range of associations is unknown. We implemented a novel method (“medical condition-wide association study,” MedWAS) to comprehensively evaluate medical risk factors for NHL documented in administrative health claims. Methods: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we conducted a case–control study comparing NHL cases [N = 52,691, age 66+ years, with five subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, marginal zone lymphoma (MZL), T-cell lymphoma (TCL)] to controls (N = 200,000). We systematically screened for associations with 5,926 medical conditions documented in Medicare claims more than 1 year before selection. Results: Fifty-five conditions were variously associated with NHL. Examples include well-established associations of human immunodeficiency virus, solid organ transplantation, and hepatitis C virus with increased DLBCL risk (ORs 3.83, 4.27, and 1.74, respectively), and autoimmune conditions with DLBCL and MZL (e.g., ORs of 2.10 and 4.74, respectively, for Sjögren syndrome). Risks for all NHL subtypes were increased after diagnoses of nonmelanoma skin cancer (ORs 1.19–1.55), actinic keratosis (1.12–1.25), or hemolytic anemia (1.64–4.07). Nine additional skin conditions increased only TCL risk (ORs 2.20–4.12). Diabetes mellitus was associated with increased DLBCL risk (OR 1.09). Associations varied significantly across NHL subtypes for 49 conditions (89%). Conclusion: Using an exploratory method, we found numerous medical conditions associated with NHL risk, and many associations varied across NHL subtypes. Impact: These results point to etiologic heterogeneity among NHL subtypes. MedWAS is a new method for assessing the etiology of cancer and other diseases. Cancer Epidemiol Biomarkers Prev; 25(7); 1105–13. ©2016 AACR.

Purpose The biology of HIV-associated cancers may differ depending on immunologic and virologic context during development. Therefore, an understanding of the burden of Kaposi's sarcoma (KS) and non-Hodgkin lymphoma (NHL) relative to antiretroviral therapy (ART), virologic suppression, and CD4 count is important. Patients and Methods KS and NHL diagnoses during 1996 to 2011 were identified among patients with HIV infection in eight clinical cohorts in the United States. Among patients in routine HIV clinical care, the proportion of cases in categories of ART use, HIV RNA, and CD4 count at diagnosis were described across calendar time. Person-time and incidence rates were calculated for each category. Results We identified 466 patients with KS and 258 with NHL. In recent years, KS was more frequently diagnosed after ART initiation (55% in 1996 to 2001 v 76% in 2007 to 2011; P-trend = .02). The proportion of patients with NHL who received ART was higher but stable over time (83% overall; P-trend = .81). An increasing proportion of KS and NHL occurred at higher CD4 counts (P < .05 for KS and NHL) and with undetectable HIV RNA (P < .05 for KS and NHL). In recent years, more person-time was contributed by patients who received ART, had high CD4 counts and had undetectable HIV RNA, whereas incidence rates in these same categories remained stable or declined. Conclusion Over time, KS and NHL occurred at higher CD4 counts and lower HIV RNA values, and KS occurred more frequently after ART initiation. These changes were driven by an increasing proportion of patients with HIV who received effective ART, had higher CD4 counts, and had suppressed HIV RNA and not by increases in cancer risk within these subgroups. An improved understanding of HIV-associated cancer pathogenesis and outcomes in the context of successful ART is therefore important.

The associations of acute HIV infection (AHI) and other predictors with transmitted drug resistance (TDR) prevalence were assessed in a cohort of HIV-infected, antiretroviral-naïve patients. AHI was defined as being seronegative with detectable HIV RNA. Binomial regression was used to estimate prevalence ratios and 95% confidence intervals for associations with TDR. Among 43 AHI patients, TDR prevalence was 20.9%, whereas prevalence was 8.6% among 677 chronically infected patients. AHI was associated with 1.9 times the prevalence of TDR (95% confidence intervals: 1.0 to 3.6) in multivariable analysis. AHI patients may represent a vanguard group that portends increasing TDR in the future.

It is suspected that primary central nervous system lymphoma (PCNSL) rates are increasing among immunocompetent people. We estimated PCNSL trends in incidence and survival among immunocompetent persons by excluding cases among human immunodeficiency virus (HIV)-infected persons and transplant recipients. PCNSL data were derived from 10 Surveillance, Epidemiology and End Results (SEER) cancer registries (1992–2011). HIV-infected cases had reported HIV infection or death due to HIV. Transplant recipient cases were estimated from the Transplant Cancer Match Study. We estimated PCNSL trends overall and among immunocompetent individuals, and survival by HIV status. A total of 4,158 PCNSLs were diagnosed (36% HIV-infected; 0.9% transplant recipients). HIV prevalence in PCNSL cases declined from 64.1% (1992–1996) to 12.7% (2007–2011), while the prevalence of transplant recipients remained low. General population PCNSL rates were strongly influenced by immunosuppressed cases, particularly in 20–39 year-old men. Among immunocompetent people, PCNSL rates in men and women aged 65+ years increased significantly (1.7% and 1.6%/year), but remained stable in other age groups. Five-year survival was poor, particularly among HIV-infected cases (9.0%). Among HIV-uninfected cases, 5-year survival increased from 19.1% (1992–1994) to 30.1% (2004–2006). In summary, PCNSL rates have increased among immunocompetent elderly adults, but not in younger individuals. Survival remains poor for both HIV-infected and HIV-uninfected PCNSL patients.

Background and objectives: Proteinuria is a major determinant of chronic kidney disease. We aimed to characterize the prevalence and correlates of proteinuria in a cohort of HIV-infected and uninfected injection drug users. Design, setting, participants, & measurements: A cross-sectional analysis was performed among 902 injection drug users (273 HIV-infected) in the AIDS Linked to the Intravenous Experience cohort. The primary outcome was proteinuria defined as having a urine protein/creatinine concentration ratio >200 mg/g. Poisson regression with robust variance was used to determine prevalence ratios. Results: Overall, 24.8% of participants had proteinuria; the prevalence was 2.9 times higher among HIV-infected participants (45%) compared with HIV-uninfected participants (16%). In addition, age, health insurance, employment status, hepatitis B and C serostatus, diabetes, and high BP were associated with proteinuria. Neither antiretroviral therapy nor features of illicit drug use history were associated with proteinuria. In multivariate analysis, HIV infection, unemployment, increased age, diabetes, hepatitis C infection, and high BP were significantly associated with a higher prevalence of proteinuria. Conclusions: In an aging, predominantly African-American cohort of injection drug users, we found a striking burden of proteinuria that was strongly associated with HIV status. In addition to being a pathway to ESRD, proteinuria is a potent risk factor for cardiovascular morbidity and mortality. Evaluation of aggressive screening and disease-modification strategies in this high-risk population is warranted.

A community-based, cluster-randomized, placebo-controlled trial of daily zinc and/or iron+folic acid supplementation was conducted in rural southern Nepal to examine motor milestone attainment among 3264 children 1–36 mo of age between 2001 and 2006. Treatment groups included placebo, zinc (10 mg), iron+folic acid (12.5 mg iron + 50 mg folic acid), and zinc +iron+folic acid (10 mg zinc + 12.5 mg iron + 50 mg folic acid). Infants received half of these doses. The iron arms were stopped November 2003 by recommendation of the Data Safety and Monitoring Board; zinc and placebo continued until January 2006. A total of 2457 children had not walked at the time of entry into the trial and 1775 were followed through 36 mo. Mean age at first walking unassisted did not differ among groups and was 444 6 81 d (mean 6 SD) in the placebo group, 444 6 81 d in the zinc group, 464 6 85 d in the iron+folic acid group, and 446 6 87 d in the iron+folic acid+zinc group. Results were similar after adjustment for age at enrollment, asset ownership, maternal literacy, and prior child deaths in the household and in children who consumed at least 60 tablets. Compared with placebo, iron+folic acid was associated with an adjusted mean delay of 28.0 d (95% CI: 11.3, 44.7) in time to walking among infants and the delay was more pronounced with mid-upper arm circumference (MUAC) , 9.5 cm [60.6 d, (95% CI: 28.5, 92.6)]. Risks and benefits of universal iron+folic acid supplementation of infants beyond improved hematologic status deserve further consideration. J. Nutr. 140: 1317–1321, 2010.

Exposure to indoor air pollution due to open burning of biomass fuel is common in low- and middle-income countries. Previous studies linked this exposure to an increased risk of respiratory illness, low birth weight (LBW) and other disorders. We assessed the association between exposure to biomass fuel sources and second-hand tobacco smoke (SHTS) in the home and adverse health outcomes in early infancy in a population in rural south India.A population-based cohort of newborns was followed from birth through 6 months. Household characteristics were assessed during an enrolment interview including the primary type of cooking fuel and smoking behaviour of household residents. Follow-up visits for morbidity were carried out every 2 weeks after delivery. Infants were discharged at 6 months when anthropometric measurements were collected.11 728 live-born infants were enrolled and followed, of whom 92.3% resided in households that used wood and/or dung as a primary source of fuel. Exposure to biomass fuel was associated with an adjusted 49% increased risk of LBW, a 34% increased incidence of respiratory illness and a 21% increased risk of 6-month infant mortality. Exposed infants also had 45 and 30% increased risks of underweight and stunting at 6 months. SHTS exposure was also associated with these adverse health outcomes except for attained growth.Open burning of biomass fuel in the home is associated with significant health risks to the newborn child and young infant. Community-based trials are needed to clarify causal connections and identify effective approaches to reduce this burden of illnesses.

This study aimed to identify risk factors associated with maternal night blindness in rural South India.At delivery, women enrolled in a population-based trial of newborn vitamin A supplementation were asked whether they were night blind at any time during the pregnancy. Multivariate logistic regression was used to identify socioeconomic, demographic, and pregnancy-related factors associated with maternal night blindness.Women reported night blindness in 687 (5.2%) of 13,171 pregnancies. In a multivariate model, having a concrete roof (Odds Ratio (OR): 0.60, 95% Confidence Interval (CI): 0.47, 0.78), religion other than Hindu (OR: 0.46, 95% CI: 0.27, 0.76), maternal literacy (OR: 0.58, 95% CI: 0.49, 0.69), and maternal age from 25 to 29 years (OR: 0.68, 95% CI: 0.50, 0.93) were associated with a lower risk of night blindness in pregnancy. The odds of night blindness were higher for those leasing rather than owning land (OR: 1.78, 95%CI: 1.08, 2.93), parity 6 or more compared to 0 (OR: 2.11, 95% CI: 1.09, 4.08), and with twin pregnancies (OR: 3.23, 95% CI: 1.93, 5.41). Factors not associated with night blindness in the multivariate model were other markers of socioeconomic status such as electricity in the house, radio and television ownership, type of cooking fuel and household transportation, and number of children under 5 years of age in the household.Maternal night blindness was prevalent in this population. Being pregnant with twins and of higher parity put women at higher risk. Maternal literacy and higher socioeconomic status lowered the risk.

For recipients of liver transplantations (LTs) for hepatocellular carcinoma (HCC), HCC recurrence after transplantation remains a major concern. Sirolimus (SRL), an immunosuppressant with anticarcinogenic properties, may reduce HCC recurrence and improve survival. In our study, the US Scientific Registry of Transplant Recipients was linked to pharmacy claims. For liver recipients transplanted for HCC, Cox regression was used to estimate associations of early SRL use with recurrence, cancer-specific mortality, and all-cause mortality, adjusting for recipient ethnicity, calendar year of transplant, total tumor volume, alpha-fetoprotein, transplant center size, use of interleukin 2 induction therapy, and allocated and calculated Model for End-Stage Liver Disease score. We performed stratified analyses among recipients who met Milan criteria, among those without renal failure, among those with deceased liver donors, by age at transplantation, and by tumor size. Among the 3936 included HCC LTs, 234 (6%) were SRL users. In total, there were 242 recurrences and 879 deaths, including 261 cancer-related deaths. All-cause mortality was similar in SRL users and nonusers (adjusted hazard ratio [aHR], 1.01; 95% CI, 0.73-1.39). HCC recurrence and cancer-specific mortality rates appeared lower in SRL users, but associations were not statistically significant (recurrence aHR, 0.86; 95% CI, 0.45-1.65; cancer-specific mortality aHR, 0.80; 95% CI, 0.43-1.50). Among recipients >55 years old, associations were suggestive of better outcomes for SRL users (all-cause mortality aHR, 0.62; 95% CI, 0.38-1.01; recurrence aHR, 0.52; 95% CI, 0.19-1.44; cancer-specific mortality aHR, 0.34; 95% CI, 0.11-1.09), whereas among recipients ≤55 years old, SRL users had worse outcomes (all-cause mortality aHR, 1.76; 95% CI, 1.12-2.75; recurrence aHR, 1.49; 95% CI, 0.62-3.61; cancer-specific mortality aHR, 1.54; 95% CI, 0.71-3.32). In conclusion, among HCC liver recipients overall, SRL did not appear beneficial in reducing all-cause mortality. However, there were suggestions of reductions in recurrence and cancer-specific mortality, and effects appeared to be modified by age at transplantation. Liver Transplantation 22 627-634 2016 AASLD.

The effects of pediatric solid organ transplantation on cancer risk may differ from those observed in adult recipients. We described cancers in pediatric recipients and compared incidence to the general population.The US transplant registry was linked to 16 cancer registries to identify cancer diagnoses among recipients18 years old at transplant. Standardized incidence ratios (SIRs) were estimated by dividing observed cancer counts among recipients by expected counts based on the general population rates. Cox regression was used to estimate the associations between recipient characteristics and non-Hodgkin's lymphoma (NHL) risk.Among 17 958 pediatric recipients, 392 cancers were diagnosed, of which 279 (71%) were NHL. Compared with the general population, incidence was significantly increased for NHL (SIR = 212, 95% confidence interval [CI] = 188-238), Hodgkin's lymphoma (SIR = 19, 95% CI = 13-26), leukemia (SIR = 4, 95% CI = 2-7), myeloma (SIR = 229, 95% CI = 47-671), and cancers of the liver, soft tissue, ovary, vulva, testis, bladder, kidney, and thyroid. NHL risk was highest during the first year after transplantation among recipients5 years old at transplant (SIR = 313), among recipients seronegative for Epstein-Barr virus (EBV) at transplant (SIR = 446), and among intestine transplant recipients (SIR = 1280). In multivariable analyses, seronegative EBV status, the first year after transplantation, intestine transplantation, and induction immunosuppression were independently associated with higher NHL incidence.Pediatric recipients have a markedly increased risk for many cancers. NHL constitutes the majority of diagnosed cancers, with the highest risk occurring in the first year after transplantation. NHL risk was high in recipients susceptible to primary EBV infection after transplant and in intestine transplant recipients, perhaps due to EBV transmission in the donor organ.

Cancer has been linked to HIV since the earliest days of the epidemic. The unusually frequent occurrence of Kaposi sarcoma (KS) among men who have sex with men (MSM) in 1981 was a sentinel observation leading to the inclusion of KS in the first AIDS case definition.1,2 More than three decades later, major research investments have led to striking advances in understanding HIV pathogenesis, with antiretroviral therapy (ART) reducing AIDS complications and allowing HIV-infected individuals to experience life expectancy approaching that of persons without HIV.3,4

Background. Lymphoma incidence is increased among human immunodeficiency virus (HIV)–infected individuals soon after antiretroviral therapy (ART), perhaps due to unmasking immune reconstitution inflammatory syndrome (IRIS). Clinical characteristics and survival for unmasking lymphoma IRIS have not been described. Methods. We studied lymphoma patients in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) from 1996 until 2011. Unmasking lymphoma IRIS was defined as lymphoma within 6 months after ART accompanied by a ≥0.5 log10 copies/mL HIV RNA reduction. Differences in presentation and survival were examined between IRIS and non-IRIS cases. Results. Of 482 lymphoma patients, 56 (12%) met criteria for unmasking lymphoma IRIS. Of these, 12 (21%) had Hodgkin lymphoma, 22 (39%) diffuse large B-cell lymphoma, 5 (9%) Burkitt lymphoma, 10 (18%) primary central nervous system lymphoma, and 7 (13%) other non-Hodgkin lymphoma. Median CD4 cell count at lymphoma diagnosis among IRIS cases was 173 cells/µL (interquartile range, 73–302), and 48% had suppressed HIV RNA

Objective: Toestimatetheassociationbetween immunologicresponseto antiretroviral therapy (ART) and non-AIDS defining cancer (NADC) incidence in HIV-infected patients. Design: A prospective cohort including patients with at least 1cell/ml CD4 þ cell count and HIV-1 RNA measure after ART initiation between 1996 and 2011 in the Centers for AIDS Research Network of Integrated Clinical Systems, a collaboration of eight HIV clinics at major academic medical centres in the United States. Methods: Measures of immunologic response were 6-month CD4 þ post-ART, latest CD4 þ and CD4 þ count-years, a cumulative measure of CD4 þ lymphopenia. Cox regression with inverse probability-of-exposure weights was used to calculate adjusted hazard ratios of virus-related and virus-unrelated NADC incidence. Results: Among 9389patients atART initiation,median CD4 þ cell countwas 200cells/ ml [interquartile range (IQR) 60‐332)], and median HIV-1 RNA was 4.8log10copies/ml (IQR 4.3‐5.4). Median follow-up was 3.3 years (IQR 1.5‐6.5). After 6 months of ART, median CD4 þ cell count was 304cells/ml (IQR 163‐469). One hundred and sixty-four NADCs were diagnosed during study follow-up, 65 (40%) considered virus-related. Virus-related NADCs were inversely associated with 6-month CD4 þ cell count (hazard ratio per 100cells/ml increase ¼0.71), latest CD4 þ cell count (hazard ratio per 100cells/ml increase ¼0.70) and CD4 þ cell count-years (hazard ratio per 200cellyears/ml increase ¼0.91) independent of CD4 þ cell count at ART initiation, age and HIV-1 RNA response. No associations were found with virus-unrelated NADCs. Conclusion: Poor CD4 þ cell count response was strongly associated with virus-related NADC incidence, suggesting an important role for T-cell mediated immunity in pathogenesis. Lower CD4 þ cell count proximal to cancer diagnosis may be a result of subclinical cancer. Intensified cancer screening should be considered for patients on ART with low CD4 þ cell counts.

BackgroundLymphoma is the leading cause of cancer-related death among HIV-infected patients in the antiretroviral therapy (ART) era.MethodsWe studied lymphoma patients in the Centers for AIDS Research Network of Integrated Clinical Systems from 1996 until 2010. We examined differences stratified by histology and diagnosis year. Mortality and predictors of death were analyzed using Kaplan-Meier curves and Cox proportional hazards.ResultsOf 23 050 HIV-infected individuals, 476 (2.1%) developed lymphoma (79 [16.6%] Hodgkin lymphoma [HL]; 201 [42.2%] diffuse large B-cell lymphoma [DLBCL]; 56 [11.8%] Burkitt lymphoma [BL]; 54 [11.3%] primary central nervous system lymphoma [PCNSL]; and 86 [18.1%] other non-Hodgkin lymphoma [NHL]). At diagnosis, HL patients had higher CD4 counts and lower HIV RNA than NHL patients. PCNSL patients had the lowest and BL patients had the highest CD4 counts among NHL categories. During the study period, CD4 count at lymphoma diagnosis progressively increased and HIV RNA decreased. Five-year survival was 61.6% for HL, 50.0% for BL, 44.1% for DLBCL, 43.3% for other NHL, and 22.8% for PCNSL. Mortality was associated with age (adjusted hazard ratio [AHR] = 1.28 per decade increase, 95% confidence interval [CI] = 1.06 to 1.54), lymphoma occurrence on ART (AHR = 2.21, 95% CI = 1.53 to 3.20), CD4 count (AHR = 0.81 per 100 cell/µL increase, 95% CI = 0.72 to 0.90), HIV RNA (AHR = 1.13 per log10copies/mL, 95% CI = 1.00 to 1.27), and histology but not earlier diagnosis year.ConclusionsHIV-associated lymphoma is heterogeneous and changing, with less immunosuppression and greater HIV control at diagnosis. Stable survival and increased mortality for lymphoma occurring on ART call for greater biologic insights to improve outcomes.

We assessed laboratory monitoring after combination antiretroviral therapy initiation among 3678 patients in a large US multisite clinical cohort, censoring participants at last clinic visit, combination antiretroviral therapy change, or 3 years. Median days (interquartile range) to first hematologic, hepatic, renal, and lipid tests were 30 (18-53), 31 (19-56), 33 (20-59), and 350 (96-1106), respectively. At 1 year, approximately 80% received more than 2 hematologic, hepatic, and renal tests consistent with guidelines. However, only 40% received 1 or more lipid tests. Monitoring was more frequent in specific subgroups, likely reflecting better clinic attendance or clinician perception of higher susceptibility to toxicities.

BackgroundCancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized.MethodsWe evaluated the incidence and timing of cancer diagnoses among patients initiating ART between 1996 and 2011 in a collaboration of 8 US clinical HIV cohorts. Poisson regression was used to estimate incidence rates. Cox regression was used to identify demographic and clinical characteristics associated with cancer incidence after ART initiation.ResultsAt initiation of first combination ART among 11 485 patients, median year was 2004 (interquartile range [IQR], 2000-2007) and median CD4 count was 202 cells/mm(3) (IQR, 61-338). Incidence rates for Kaposi sarcoma (KS) and lymphomas were highest in the first 6 months after ART initiation (P < .001) and plateaued thereafter, while incidence rates for all other cancers combined increased from 416 to 615 cases per 100 000 person-years from 1 to 10 years after ART initiation (average 7% increase per year; 95% confidence interval, 2%-13%). Lower CD4 count at ART initiation was associated with greater risk of KS, lymphoma, and human papillomavirus-related cancer. Calendar year of ART initiation was not associated with cancer incidence.ConclusionsKS and lymphoma rates were highest immediately following ART initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART, likely reflecting increased cancer risk with aging. Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation along with ongoing aggressive cancer screening and prevention efforts throughout the course of HIV care.

Tumors may evade immune attack by constitutive (oncogene-driven) and/or adaptive (IFN-g inducible) expression of PD-L1. PD-1/PD-L1 blockade can mediate tumor regression in immunocompetent patients. In HIV-infected patients, developing tumors may face little immune selection pressure and therefore may not evolve to evade immune attack. Expression of PD-L1 has not been systematically assessed in cancers from HIV-infected people. In the current study, immunohistochemistry for PD-L1, and CD3 and CD68 (immune cells, ICs) was performed on biopsies from 46 anal SCCs, including 27 from HIV-infected and 19 from uninfected patients. The proportion of cases with tumor cell PD-L1 expression was similar in patients with and without HIV (52% vs. 47%, respectively, p = 0.76), as was the presence of moderate/severely dense ICs (33% vs. 37%, p = 0.81) (Table). Among HIV-infected patients, 19% of anal SCC tumors (5/27) both expressed PD-L1 and had moderate/severe IC infiltration. Tumors from HIV-infected and uninfected patients had similar densities of CD68+ macrophages (mean 517 vs. 404 cells/mm2, p = 0.33) and CD3+ T- lymphocytes (mean 501 vs. 428 cells/mm2, p = 0.57). A component of adaptive PD-L1 expression (juxtaposed to tumor infiltrating ICs) was also observed in both groups (56% vs. 47%, p = 0.58), consistent with comparable T-cell functionality. Further studies will explore the expression of other immune checkpoint proteins and lymphocyte subsets. Despite expectations that cancers from HIV-infected patients would show reduced inflammation, our preliminary findings demonstrate an immune-reactive microenvironment in both HIV+ and HIV- anal SCCs and suggest that anti-PD-1/PD-L1 therapies should be evaluated in anal SCC patients. Tumor infiltrating ICTotalHIV- a (n = 19)HIV+ a (n = 27)P-value cNone-mildTotal3012 (40%)18 (60%)0.66PD-L1(+) b145 (36%)9 (64%)PD-L1(-)167 (44%)9 (56%)Moderate-severeTotal167 (44%)9 (56%)0.95PD-L1(+) b94 (44%)5 (56%)PD-L1(-)73 (43%)4 (57%)a Anal SCC tumors in HIV-infected patients include 19 tumors identified through the AIDS-Cancer Specimen Resource and 8 tumors identified at Johns Hopkins Hospital. Anal SCC tumors in HIV-uninfected patients include 1 tumor identified through the AIDS-Cancer Specimen Resource and 18 tumors identified at Johns Hopkins Hospital.b Defined as ≥5% of tumor cells expressing cell surface PD-L1 by immunohistochemistry with the 5H1 monoclonal antibody.c P-values are for the comparison of PD-L1 expression between HIV+ and HIV- anal SCCs within strata of tumor infiltrating ICIC = immune cells Citation Format: Elizabeth L. Yanik, Suzanne L. Topalian, Genevieve Kaunitz, Jessica Esandrio, Tricia Cottrell, Janis M. Taube. The tumor immune microenvironment is similar in anal squamous cell carcinomas (SCCs) from HIV-infected and uninfected patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1464.

Elevated risk of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the skin has been identified in a number of clinical populations with conditions affecting the immune system, such as organ transplant recipients and non-Hodgkin lymphoma patients. However, because many other immune-related conditions are rare, their relationships with SCC and BCC have not been studied. We used Medicare claims to identify SCC and BCC cases in 2012 and to select controls in 2012 matched on sex and age with a 10:1 ratio. All subjects were of white race. For cases and controls, we used Medicare claims during 1999-2011 to identify 44 immune-related conditions (immunosuppressive conditions, autoimmune diseases, hematologic malignancies, and allergic diseases). The statistical significance of associations was determined after Bonferroni correction for multiple comparisons. In Medicare in 2012, there were a total of 470,756 SCC and 601,863 BCC cases. Of the 44 immune-related conditions included, SCC was associated with 41 (93%) and BCC was associated with 31 (70%). For most conditions, SCC was more strongly associated than BCC. We identified significant associations of SCC and BCC risk with well-characterized conditions, such as HIV, rheumatoid arthritis, and allergic rhinitis (SCC odds ratios (ORs) of 1.64, 1.29, and 1.29, respectively; BCC ORs of 1.60, 1.10, and 1.22; Table), as well as with poorly characterized or rare conditions, such as deficiency of cell-mediated immunity and polyarteritis nodosa (SCC ORs of 2.87 and 1.92; BCC ORs of 1.55 and 1.49). In conclusion, most immune-related conditions in our study indicated an elevated risk of non-melanoma skin cancer, particularly SCC. These findings provide evidence that immune dysfunction, as manifest across a wide range of conditions, may play an important role in development of SCC and BCC. Possible mechanisms could include direct effects of immune-related conditions or their treatments. Results from a sample of the immune-related conditions assessedSquamous cell carcinomaBasal cell carcinomaImmune-related conditionsN cases (%)OR95% CIp-valueN cases (%)OR95% CIp-valueTotal470756601863Immunosuppressive conditionsDeficiency of humoral immunity1550 (0.33)2.552.41-2.69 Citation Format: Elizabeth L. Yanik, Ruth M. Pfeiffer, D. Michal Freedman, Eric A. Engels. Associations of immune-related conditions with squamous cell and basal cell skin cancer risk. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3443.

Introduction Cohort studies have demonstrated increased incidence of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) among HIV-infected individuals during the first 6 months after antiretroviral therapy (ART) initiation, perhaps due to unmasking immune reconstitution inflammatory syndrome (IRIS). Unmasking IRIS is characterized by the diagnosis of a new HIV-associated condition soon after ART that was not apparent prior to ART, coupled with evidence of ART effectiveness. It has been well described for opportunistic infections and Kaposi sarcoma. However, clinical characteristics and survival for unmasking lymphoma IRIS have not been described. Methods We studied lymphoma patients in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) from 1996 until 2011. Unmasking lymphoma IRIS was defined as HL or NHL occurring within 6 months after ART initiation accompanied by a ≥0.5 log10copies/mL reduction in HIV RNA between values taken prior to ART and at lymphoma diagnosis. Differences in presentation and survival were examined between lymphoma IRIS and non-IRIS cases. Results Of 482 lymphoma patients, 48 (10%) met criteria for unmasking lymphoma IRIS. Of these, 10 (21%) had HL, 19 (40%) diffuse large B-cell lymphoma (DLBCL), 4 (8%) Burkitt lymphoma (BL), 9 (19%) primary central nervous system lymphoma (PCNSL), and 6 (12%) other NHL (Table). Median CD4 cell count at lymphoma diagnosis among IRIS cases was 163 cells/mL (interquartile range 67-302), and 54% had suppressed HIV RNA (< 400 copies/ml). No significant differences were identified between lymphoma IRIS and non-IRIS cases, with the exception of possible earlier stage (47% stage I/II versus 24%, p=0.03), more frequent hepatitis B/C co-infection (31% versus 19%, p=0.05), and more frequent prior AIDS illness (92% versus 79%, p=0.05), as well as expected lower HIV RNA at lymphoma diagnosis likely resulting from the IRIS case definition. Additionally, no differences in cumulative mortality 5 years after lymphoma diagnosis were identified between IRIS and non-IRIS cases, although there was a suggestion of increased early mortality among IRIS cases (Figure). Conclusions In a large HIV-associated lymphoma cohort in the United States, 10% of patients met a standardized unmasking lymphoma IRIS case definition. No major differences between lymphoma IRIS and non-IRIS cases were identified. Possible effects of subclinical lymphoma leading to care seeking behavior and subsequent ART initiation prior to lymphoma diagnosis could not be excluded. Disclosures: No relevant conflicts of interest to declare.

Background In HIV-infected populations in developed countries, the most recent published cancer incidence trend analyses are only updated through 2008. We assessed changes in the distribution of cancer types and incidence trends among HIV-infected patients in North Carolina up until 2011. Methods We linked the University of North Carolina Center for AIDS Research HIV Clinical Cohort, an observational clinical cohort of 3141 HIV-infected patients, with the North Carolina Cancer registry. Cancer incidence rates were estimated across calendar years from 2000 to 2011. The distribution of cancer types was described. Incidence trends were assessed with linear regression. Results Across 15,022 person-years of follow-up, 202 cancers were identified (incidence rate per 100,000 person-years [IR]: 1345; 95% confidence interval [CI]: 1166, 1544). The majority of cancers were virus-related (61%), including Kaposi sarcoma (N = 32) (IR: 213; 95%CI: 146, 301), non-Hodgkin lymphoma (N = 34) (IR: 226; 95%CI: 157, 316), and anal cancer (N = 16) (IR: 107; 95%CI: 61, 173). Non-Hodgkin lymphoma was observed to decrease from 2000 to 2011 (decline of 15 cases per 100,000 person-years per calendar year, 95%CI: -27, -3). No other changes in incidence or changes in incidence trends were observed for other cancers (all P > 0.20). Conclusions We observed a substantial burden of a variety of cancers in this population in the last decade. Kaposi sarcoma and non-Hodgkin lymphoma were consistently two of the greatest contributors to cancer burden across calendar time. Cancer rates appeared stable across calendar years, except for non-Hodgkin lymphoma, which appeared to decrease throughout the study period.