Publications by authors named "Anna E Coghill"

50 Publications

An updated systematic review of HPV genotype distribution by cervical disease grade in women living with HIV highlights limited findings from Latin America.

Sex Transm Dis 2021 Mar 12. Epub 2021 Mar 12.

1Center for Immunization and Infection Research in Cancer, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA, 33612 2Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA, 33612 3Weill Cornell Medicine, New York, NY 4Instituto do Cancer do Estado de São Paulo, São Paulo, Brazil 5Department of Radiology and Oncology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Cervical cancer is five times more likely among women living with HIV (WHIV), likely due to higher prevalence of HPV. Despite evidence of higher rates with multiple HPV genotypes in WHIV, there are no recommendations for triage by HPV genotyping specific to WHIV. In Latin America/Caribbean (LAC) rates are high and vary significantly. To guide optimization of HPV-based cervical cancer screening among WHIV in LAC, review of current literature was completed to assess HPV genotype distribution by cervical disease grade in WHIV in this region; and further expanded globally for comparison across regions.A systematic review of the literature from June 2016 to January 2020 revealed 15 studies reporting HPV genotype distribution by cervical disease state (normal, low-grade disease, high-grade disease, and invasive cervical cancer) across different global regions.Across all studies, there were 6,928 WHIV from 4 global regions, 3,952 of whom were HPV-positive. Three studies from LAC were reviewed, with one providing enough detail to describe HPV genotypes by cervical disease grade and identified type 31 and 35 in high-grade cervical lesions. Of the studies included, 4 from Africa and Europe/North America each, and 1 from Asia included data that were able to be summarized.Latin America, a region which experiences high rates of HPV, HIV, and cervical disease, had few published studies reporting HPV genotypes by cervical disease grade, with one reporting individual HPV genotype and specific cervical disease grade. Identifying HPV types associated with CIN2+ in WHIV in this region has the potential to improve screening and treatment for cervical cancer prevention and should be the focus of future research.
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http://dx.doi.org/10.1097/OLQ.0000000000001412DOI Listing
March 2021

Prospective investigation of polyomavirus infection and the risk of adult glioma.

Sci Rep 2021 May 5;11(1):9642. Epub 2021 May 5.

Infections and Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120, Heidelberg, Germany.

Glioma is an aggressive primary tumor of the brain with a poorly understood etiology. We studied the association of 4 human polyomaviruses (HPyV)-JC virus (JCV), BK virus (BKV), human polyomavirus 6 (HPyV6), and Merkel cell polyomavirus (MCPyV) with glioma risk within the Cancer Prevention Study II in the US (CPS-II) and the Janus Serum Bank in Norway. Cohort participants subsequently diagnosed with glioma from the CPS-II (n = 37) and Janus Serum Bank (n = 323), a median of 6.9 and 15.4 years after blood collection, respectively, were matched to individual controls on age, sex, and date of blood draw. Serum antibodies to the major viral capsid protein (VP1) were used to establish infection history for each polyomavirus. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. In the Janus Serum Bank, MCPyV infection was associated with a higher risk of glioma overall (OR: 1.56; 95% CI 1.10, 2.19). A modest, nonsignificant positive association with MCPyV infection was also observed in CPS-II (OR: 1.29; 95% CI 0.54, 3.08). In both cohorts, glioma risk was not significantly related to infection with JCV, BKV or HPyV6. The present study suggests that MCPyV infection may increase glioma risk.
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http://dx.doi.org/10.1038/s41598-021-89133-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100283PMC
May 2021

Toxoplasma gondii infection and the risk of adult glioma in two prospective studies.

Int J Cancer 2021 Jan 11. Epub 2021 Jan 11.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.

Toxoplasma gondii (T gondii) is a common parasite that shows affinity to neural tissue and may lead to the formation of cysts in the brain. Previous epidemiologic studies have suggested an association between glioma and increased prevalence of T gondii infection, but prospective studies are lacking. Therefore, we examined the association between prediagnostic T gondii antibodies and risk of glioma in two prospective cohorts using a nested case-control study design. Cases and matched controls were selected from the American Cancer Society's Cancer Prevention Study-II Nutrition Cohort (CPSII-NC) (n = 37 cases and 74 controls) and the Norwegian Cancer Registry's Janus Serum Bank (Janus) (n = 323 cases and 323 controls). Blood samples collected prior to diagnosis were analyzed for antibodies to two T gondii surface antigens (p22 and sag-1), with individuals considered seropositive if antibodies to either antigen were detected. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for each cohort. In both cohorts, a suggestive increase in glioma risk was observed among those infected with T gondii (OR: 2.70; 95% CI: 0.96-7.62 for CPSII-NC; OR: 1.32, 95% CI: 0.85-2.07 for Janus), particularly among participants with high antibody titers specific to the sag-1 antigen (CPSII-NC OR: 3.35, 95% CI: 0.99-11.38; Janus OR: 1.79, 95% CI: 1.02-3.14). Our findings provide the first prospective evidence of an association between T gondii infection and risk of glioma. Further studies with larger case numbers are needed to confirm a potential etiologic role for T gondii in glioma.
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http://dx.doi.org/10.1002/ijc.33443DOI Listing
January 2021

Epstein-Barr Virus-Based Nasopharyngeal Carcinoma (NPC) Risk Prediction Scores Are Elevated in NPC Multiplex Family Members in Taiwan.

J Infect Dis 2021 Feb;223(3):441-444

Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Nasopharyngeal carcinoma (NPC) is caused by Epstein-Barr virus (EBV) and is more likely to occur in susceptible families. Whether genetic susceptibility operates through altered EBV control is incompletely understood. We used a NPC risk prediction model based on 14 EBV markers to compare risk score distribution in unaffected members from multiplex families with that in population-based controls. Despite the absence of NPC at the time of antibody measurement, we observed an upward shift in risk score among multiplex family members compared to the general population, consistent with the possibility that genetic factors affect NPC risk through alterations in EBV control.
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http://dx.doi.org/10.1093/infdis/jiaa385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982447PMC
February 2021

Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma.

Haematologica 2021 04 1;106(4):978-986. Epub 2021 Apr 1.

Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA.

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.
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http://dx.doi.org/10.3324/haematol.2019.238634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017820PMC
April 2021

Validation of an Epstein-Barr Virus Antibody Risk Stratification Signature for Nasopharyngeal Carcinoma by Use of Multiplex Serology.

J Clin Microbiol 2020 04 23;58(5). Epub 2020 Apr 23.

Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Serological testing for nasopharyngeal carcinoma (NPC) has recently been reinvigorated by the implementation of novel Epstein-Barr virus (EBV)-specific IgA and IgG antibodies from a proteome array. Although proteome arrays are well suited for comprehensive antigen selection, they are not applicable for large-scale studies. We adapted a 13-marker EBV antigen signature for NPC risk identified by proteome arrays to multiplex serology to establish an assay for large-scale studies. Taiwanese NPC cases ( = 175) and matched controls ( = 175) were used for assay validation. Spearman's correlation was calculated, and the diagnostic value of all multiplex markers was assessed independently using the area under the receiver operating characteristic curve (AUC). Two refined signatures were identified using stepwise logistic regression and internally validated with 10-fold cross validation. Array and multiplex serology showed strong correlation for each individual EBV marker, as well as for a 13-marker combined model on continuous data. Two refined signatures with either four (LF2 and BGLF2 IgG, LF2 and BMRF1 IgA) or two (LF2 and BGLF2 IgG) antibodies on dichotomous data were identified as the most parsimonious set of serological markers able to distinguish NPC cases from controls with AUCs of 0.992 (95% confidence interval [CI], 0.983 to 1.000) and 0.984 (95% CI, 0.971 to 0.997), respectively. Neither differed significantly from the 13-marker model (AUC, 0.992; 95% CI, 0.982 to 1.000). All models were internally validated. Multiplex serology successfully validated the original EBV proteome microarray data. Two refined signatures of four and two antibodies were capable of detecting NPC with 99.2% and 98.4% accuracy.
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http://dx.doi.org/10.1128/JCM.00077-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180240PMC
April 2020

The impact of the Patient Protection and Affordable Care Act on insurance coverage and cancer-directed treatment in HIV-infected patients with cancer in the United States.

Cancer 2020 02 11;126(3):559-566. Epub 2019 Nov 11.

Duke University School of Medicine, Durham, North Carolina.

Background: To the authors' knowledge, little is known regarding the impact of the Patient Protection and Affordable Care Act (ACA) on people living with HIV and cancer (PLWHC), who have lower cancer treatment rates and worse cancer outcomes. To investigate this research gap, the authors examined the effects of the ACA on insurance coverage and receipt of cancer treatment among PLWHC in the United States.

Methods: HIV-infected individuals aged 18 to 64 years old with cancer diagnosed between 2011 and 2015 were identified in the National Cancer Data Base. Health insurance coverage and cancer treatment receipt were compared before and after implementation of the ACA in non-Medicaid expansion and Medicaid expansion states using difference-in-differences analysis.

Results: Of the 4794 PLWHC analyzed, approximately 49% resided in nonexpansion states and were more often uninsured (16.7% vs 4.2%), nonwhite (65.2% vs 60.2%), and of low income (36.3% vs 26.9%) compared with those in Medicaid expansion states. After 2014, the percentage of uninsured individuals decreased in expansion states (from 4.9% to 3%; P = .01) and nonexpansion states (from 17.6% to 14.6%; P = .06), possibly due to increased Medicaid coverage in expansion states (from 36.9% to 39.2%) and increased private insurance coverage in nonexpansion states (from 29.5% to 34.7%). There was no significant difference in cancer treatment receipt noted between Medicaid expansion and nonexpansion states. However, the percentage of PLWHC treated at academic facilities increased significantly only in expansion states (from 40.2% to 46.7% [P < .0001]; difference-in-differences analysis: 7.2 percentage points [P = .02]).

Conclusions: The implementation of the ACA was associated with improved insurance coverage among PLWHC. Lack of insurance still is common in non-Medicaid expansion states. Patients with minority or low socioeconomic status more often resided in nonexpansion states, thereby highlighting the need for further insurance expansion.
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http://dx.doi.org/10.1002/cncr.32563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980281PMC
February 2020

The Association between the Comprehensive Epstein-Barr Virus Serologic Profile and Endemic Burkitt Lymphoma.

Cancer Epidemiol Biomarkers Prev 2020 01 16;29(1):57-62. Epub 2019 Oct 16.

Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland.

Background: The discovery of Epstein-Barr virus (EBV) in Burkitt lymphoma tumors represented the first link between a virus and cancer in humans, but the underlying role of this virus in endemic Burkitt lymphoma remains unclear. Nearly all children in Burkitt lymphoma-endemic areas are seropositive for EBV, but only a small percentage develop disease. Variation in EBV-directed immunity could be an explanatory cofactor.

Methods: We examined serum from 150 Burkitt lymphoma cases and 150 controls using a protein microarray that measured IgG and IgA antibodies against 202 sequences across the entire EBV proteome. Variation in the EBV-directed antibody repertoire between Burkitt lymphoma cases and controls was assessed using unpaired tests. ORs quantifying the association between anti-EBV IgG response tertiles and Burkitt lymphoma status were adjusted for age, sex, and study year.

Results: Thirty-three anti-EBV IgG responses were elevated in Burkitt lymphoma cases compared with controls ( ≤ 0.0003). Burkitt lymphoma-associated IgG elevations were strongest for EBV proteins involved in viral replication and antiapoptotic signaling. Specifically, we observed ORs ≥4 for BMRF1 (early antigen), BBLF1 (tegument protein), BHRF1 (Bcl-2 homolog), BZLF1 (Zebra), BILF2 (glycoprotein), BLRF2 [viral capsid antigen (VCA)p23], BDLF4, and BFRF3 (VCAp18). Adjustment for malaria exposure and inheritance of the sickle cell variant did not alter associations.

Conclusions: Our data suggest that the anti-EBV serologic profile in patients with Burkitt lymphoma is altered, with strong elevations in 33 of the measured anti-EBV IgG antibodies relative to disease-free children.

Impact: The Burkitt lymphoma-specific signature included EBV-based markers relevant for viral replication and antiapoptotic activity, providing clues for future Burkitt lymphoma pathogenesis research.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954331PMC
January 2020

Evaluation of the antibody response to the EBV proteome in EBV-associated classical Hodgkin lymphoma.

Int J Cancer 2020 08 14;147(3):608-618. Epub 2019 Nov 14.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.

The humoral immune response to Epstein-Barr virus (EBV) in classical Hodgkin lymphoma (cHL) stratified by EBV tumor status is unclear. We examined IgG and IgA antibody responses against 202 protein sequences representing 86 EBV proteins using a microarray and sera from 139 EBV-positive cHL cases, 70 EBV-negative cHL cases and 141 population-based controls frequency matched to EBV-positive cHL cases on sex and age by area (UK, Denmark and Sweden). We leveraged existing data on the proportion of circulating B-cells infected by EBV and levels of serum CCL17, a chemokine secreted by cHL tumor cells, from a subset of the cHL cases in the UK. Total IgG but not IgA response level was significantly different between EBV-positive cHL cases and controls. The distinct serological response included significant elevations in 16 IgG antibodies and 2 IgA antibodies, with odds ratios observed for the following EBV proteins: LMP1 (oncogene), BcLF1 (VCAp160, two variants) and BBLF1 (two variants). Our cHL IgG signature correlated with the proportion of circulating EBV-infected B-cells, but not serum CCL17 levels. We observed no differences in the anti-EBV antibody profile between EBV-negative cHL cases and controls. BdRF1(VCAp40)-IgG and BZLF1(Zta)-IgG were identified as the serological markers best able to distinguish EBV-positive from EBV-negative cHL tumors. Our results support the hypothesis that differences in the EBV antibody profile are specific to patients with EBV-positive cHL and are not universally observed as part of a systematically dysregulated immune response present in all cHL cases.
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http://dx.doi.org/10.1002/ijc.32741DOI Listing
August 2020

Multilaboratory Assessment of Epstein-Barr Virus Serologic Assays: the Case for Standardization.

J Clin Microbiol 2019 11 23;57(11). Epub 2019 Oct 23.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

IgA antibodies targeting Epstein-Barr virus (EBV) have been proposed for screening for nasopharyngeal carcinoma (NPC). However, methods differ, and the antigens used in these assays differ considerably between laboratories. To enable formal comparisons across a range of established EBV serology assays, we created a panel of 66 pooled serum samples and 66 pooled plasma samples generated from individuals with a broad range of IgA antibody levels. Aliquots from these panels were distributed to six laboratories and were tested by 26 assays measuring antibodies against VCA, EBNA1, EA-EBNA1, Zta, or EAd antigens. We estimated the correlation between assay pairs using Spearman coefficients (continuous measures) and percentages of agreement (positive versus negative, using predefined positivity cutoffs by each assay developer/manufacturer). While strong correlations were observed between some assays, considerable differences were also noted, even for assays that targeted the same protein. For VCA-IgA assays in serum, two distinct clusters were identified, with a median Spearman coefficient of 0.41 (range, 0.20 to 0.66) across these two clusters. EBNA1-IgA assays in serum grouped into a single cluster with a median Spearman coefficient of 0.79 (range, 0.71 to 0.89). Percentages of agreement differed broadly for both VCA-IgA (12% to 98%) and EBNA1-IgA (29% to 95%) assays in serum. Moderate-to-strong correlations were observed across assays in serum that targeted other proteins (correlations ranged from 0.44 to 0.76). Similar results were noted for plasma. We conclude that standardization of EBV serology assays is needed to allow for comparability of results obtained in different translational research studies across laboratories and populations.
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http://dx.doi.org/10.1128/JCM.01107-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813000PMC
November 2019

HIV Infection, Cancer Treatment Regimens, and Cancer Outcomes Among Elderly Adults in the United States.

JAMA Oncol 2019 Sep 12;5(9):e191742. Epub 2019 Sep 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Importance: HIV-infected patients with cancer have an elevated cancer-specific mortality rate compared with HIV-uninfected patients with cancer. However, to our knowledge, studies describing this association have not adjusted in detail for cancer treatment, despite evidence of suboptimal cancer treatment in the setting of HIV.

Objective: To compare cancer-specific mortality in HIV-infected and HIV-uninfected patients with cancer after adjusting for available data on receipt of specific cancer treatments.

Design, Setting, And Participants: We used Surveillance, Epidemiology, and End Results-Medicare linked data to identify 308 268 patients in the United States (age, ≥65 years), including 288 with HIV infection, with nonadvanced cancers of the colorectum, lung, prostate, or breast diagnosed between 1996 and 2012 who received standard, stage-appropriate cancer treatment during the year after cancer diagnosis. Data analysis was done from August 2016 to September 2018.

Exposures: HIV infection identified by the presence of Medicare claims.

Main Outcomes: Overall mortality, cancer-specific mortality, and relapse or cancer-specific mortality after initial treatment.

Results: In this database study of 308 268 patients with nonadvanced cancer (168 998 men and 139 270 women; age, ≥65 years), HIV-infected patients (n = 288) had significant elevations in the overall mortality rate compared with HIV-uninfected patients for cancers of the colorectum (hazard ratio [HR], 1.73; 95% CI, 1.11-2.68; P = .02), prostate (HR, 1.58; 95% CI, 1.23-2.03; P < .01), and breast (HR, 1.50; 95% CI, 1.01-2.24; P = .05). Cancer-specific mortality was elevated for prostate (HR, 1.65; 95% CI, 0.98-2.79; P = .06) and breast cancer (HR, 1.85; 95% CI, 0.96-3.55; P = .07). Compared with their HIV-uninfected counterparts, HIV-infected men with prostate cancer also experienced significantly higher rates of relapse or death (HR, 1.32; 95% CI, 1.03-1.71; P = .03) as did HIV-infected women with breast cancer (HR, 1.63; 95% CI, 1.09-2.43; P = .02).

Conclusions And Relevance: In the United States, elderly HIV-infected patients with cancer, particularly prostate and breast cancers, have worse outcomes than HIV-uninfected patients with cancer. This disparity persists even after adjustment for administered first-course cancer treatments and will become increasingly relevant as the HIV population in the United States continues to age.
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http://dx.doi.org/10.1001/jamaoncol.2019.1742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681563PMC
September 2019

Whole-Exome Sequencing of Nasopharyngeal Carcinoma Families Reveals Novel Variants Potentially Involved in Nasopharyngeal Carcinoma.

Sci Rep 2019 07 9;9(1):9916. Epub 2019 Jul 9.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA, 20892.

Genetic susceptibility is likely involved in nasopharyngeal carcinoma (NPC), a cancer caused by Epstein-Barr virus (EBV) infection. Understanding of genetic factors involved in NPC and how they contribute to EBV-induced carcinogenesis is limited. We conducted whole-exome capture/sequencing among 251 individuals from 97 multiplex families from Taiwan (205 affected, 21 obligate carriers, and 25 unaffected) using SeqCap EZ Human Exome Library v3.0 and Illumina HiSeq. Aligned sequences were filtered to identify likely-to-be-functional deleterious variants that co-segregated with disease. Ingenuity Pathway analysis was performed. Circulating magnesium levels were measured in 13 individuals in 2 families with NIPAL1 mutations and in 197 sporadic NPC cases and 237 controls. We identified variants in 12 genes likely involved in cancer pathogenesis, viral infection or immune responses to infection. These included genes postulated to be involved in magnesium transport (NIPAL1), EBV cell entry (ITGB6), modulation of EBV infection (BCL2L12, NEDD4L), telomere biology (CLPTM1L, BRD2, HNRNPU), modulation of cAMP signaling (RAPGEF3), DNA repair (PRKDC, MLH1), and Notch signaling (NOTCH1, DLL3). Pathway based analysis demonstrated enrichment for Notch signaling genes (p-value = 0.0006). Evaluation of individuals within NIPAL1 families suggested lower serum magnesium in NPC compared to unaffected members. A significant reduction in serum magnesium levels was observed among sporadic NPC cases compared to controls (7.1% NPC/1.7% controls below normal range; OR = 4.5; 95% CI = 1.4,14) and is consistent with findings demonstrating a role for magnesium channeling in T-cell responses to EBV. We identified novel genes associated with NPC that point to new areas of inquiry to better understand genetic factors that determine the fate of viral infections and/or otherwise predisposes to NPC.
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http://dx.doi.org/10.1038/s41598-019-46137-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617453PMC
July 2019

Advanced stage at diagnosis and elevated mortality among US patients with cancer infected with HIV in the National Cancer Data Base.

Cancer 2019 08 3;125(16):2868-2876. Epub 2019 May 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

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.
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http://dx.doi.org/10.1002/cncr.32158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663596PMC
August 2019

Survival after a cancer diagnosis among solid organ transplant recipients in the United States.

Cancer 2019 03 9;125(6):933-942. Epub 2019 Jan 9.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.

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.
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http://dx.doi.org/10.1002/cncr.31782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403005PMC
March 2019

Pathology Characterization and Detection of Human Papillomavirus Type 16 in Rectal Squamous Cell Carcinomas.

Clin Gastroenterol Hepatol 2019 09 15;17(10):2129-2131. Epub 2018 Nov 15.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Rectal squamous cell carcinoma (SCC) is a rare tumor with unresolved etiology. Human immunodeficiency virus-infected individuals and solid organ transplant recipients experience >30-fold and approximately 3-fold elevated rates of rectal SCC, respectively, suggesting immunosuppression plays a role. Human immunodeficiency virus-infected homosexual men have >60-fold higher rates of rectal SCC, similar to anal SCC. These patterns, which differ from the more common rectal adenocarcinoma (AdCA), raise the possibility of shared etiology between rectal and anal SCC, with human papillomavirus type 16 (HPV16) being a likely candidate..
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http://dx.doi.org/10.1016/j.cgh.2018.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520215PMC
September 2019

Elevated antibodies against Epstein-Barr virus among individuals predicted to carry nasopharyngeal carcinoma susceptibility variants.

J Gen Virol 2018 09 5;99(9):1268-1273. Epub 2018 Jul 5.

1​Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Epstein-Barr virus (EBV) is an obligatory factor in the development of nasopharyngeal carcinoma (NPC), and anti-EBV IgA antibodies are elevated many years prior to the development of NPC. Nearly all adults are infected with EBV, but only a few develop cancer, suggesting that additional co-factors, including genetic susceptibility, must be required for the disease to manifest. Individuals were selected from the Taiwan Family Study, a cohort of 3389 individuals from NPC multiplex families. Primary analyses were conducted among 671 individuals from 69 pedigrees with the strongest family history of disease (>3 NPC-affected family members). The likelihood that a given family member carried a NPC susceptibility variant was estimated using Mendelian segregation rules, assuming a dominant mode of inheritance. We compared anti-EBV IgA antibody seropositivity between family members predicted to be carriers of NPC-linked genetic variants and those with a lower likelihood of carrying such variants. Obligate carriers of NPC susceptibility variants (100 % predicted probability of harbouring the genetic mutation) were nine-fold more likely to be anti-EBV IgA positive compared to family members predicted not to carry disease-causing variants (OR=9.2; P-trend<0.001). This elevated risk was confirmed in analyses restricted to both unaffected individuals and pedigrees with EBV-related pathway variants identified through exome sequencing. Our data indicate that family members who are more likely to carry NPC susceptibility variants are also more likely to be anti-EBNA1 IgA seropositive. Genetic susceptibility associated with control over this common herpes virus is likely a co-factor in determining which EBV-infected adults develop NPC.
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http://dx.doi.org/10.1099/jgv.0.001115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230770PMC
September 2018

Evaluation of Total and IgA-Specific Antibody Targeting Epstein-Barr Virus Glycoprotein 350 and Nasopharyngeal Carcinoma Risk.

J Infect Dis 2018 08;218(6):886-891

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.

Background: We previously reported that higher levels of antibody targeting Epstein-Barr virus (EBV) glycoprotein350 (gp350), an EBV vaccine candidate, were protective against nasopharyngeal carcinoma (NPC) in genetically high-risk families from Taiwan. The current study attempted to extend this association to a general population cohort.

Methods: We compared total and IgA-specific gp350 antibody levels in 35 incident NPC cases and 81 disease-free controls from the Cancer Screening Program in Taiwan (23943 individuals recruited 1991-1992). Luciferase immunoprecipitation assays quantified gp350 antibody.

Results: Total EBVgp350 antibody levels were not higher in individuals who remained disease free compared to those who developed NPC (P = .11). This lack of a protective gp350 association persisted for cases diagnosed ≥5 years (odds ratio [OR] = 1.05; P = .91) and <5 years (OR = 1.85; P = .40) after blood draw. IgA-specific gp350 antibody levels were higher in cases than controls (OR = 7.03; P = .001). This increased risk was most pronounced for cases diagnosed <5 years after blood draw (OR = 11.7; P = .004).

Conclusion: Unlike our prior findings in those with a strong family history of NPC, total gp350 antibody levels were not protective against NPC development in this general population setting.
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http://dx.doi.org/10.1093/infdis/jiy250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093398PMC
August 2018

Disparities and Determinants of Cancer Treatment in Elderly Americans Living With Human Immunodeficiency Virus/AIDS.

Clin Infect Dis 2018 11;67(12):1904-1911

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Background: Previous studies suggest that human immunodeficiency virus (HIV)-infected cancer patients are less likely to receive cancer treatment. The extent to which this disparity affects the growing population of elderly individuals is unknown and factors that mediate these treatment differences have not been explored.

Methods: We studied 930359 Americans aged 66-99 years who were diagnosed with 10 common cancers. Surveillance, Epidemiology, and End Results-Medicare claims from 1991 to 2011 were used to determine HIV status and receipt of cancer treatment in 6 months following diagnosis. Mediation analysis was conducted to estimate the direct effect of HIV, and indirect effect through cancer stage at diagnosis and comorbidities, on cancer treatment.

Results: HIV-infected individuals (n = 687) were less likely to receive cancer treatment (70% vs 75% HIV uninfected; P < .01). This difference was larger in individuals aged 66-70 years, among whom only 65% were treated (vs 81% in HIV uninfected; P < .01), and time from cancer diagnosis to treatment was longer (median, 42.5 vs 36 days in HIV uninfected; P < .01). Accounting for potential confounders, HIV-infected individuals aged 66-70 years remained 20% less likely to receive cancer treatment (hazard ratio, 0.81 [95% confidence interval, .71-.92]). Seventy-five percent of this total effect was due to HIV itself, with a nonsignificant 24% mediated by cancer stage and comorbidities.

Conclusions: Lowest cancer treatment rates were seen in the younger subset of HIV-infected individuals, who would likely benefit most from treatment in terms of life expectancy.
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http://dx.doi.org/10.1093/cid/ciy373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260168PMC
November 2018

Risk of Breast, Prostate, and Colorectal Cancer Diagnoses Among HIV-Infected Individuals in the United States.

J Natl Cancer Inst 2018 09;110(9):959-966

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1093/jnci/djy010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136931PMC
September 2018

Patterns of Interindividual Variability in the Antibody Repertoire Targeting Proteins Across the Epstein-Barr Virus Proteome.

J Infect Dis 2018 05;217(12):1923-1931

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Background: Little is known about variation in antibody responses targeting the full spectrum of Epstein-Barr virus (EBV) proteins and how such patterns inform disease risk.

Methods: We used a microarray to measure immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody responses against 199 EBV protein sequences from 5 EBV strains recovered from 289 healthy adults from Taiwan. We described positivity patterns, estimated the correlation between antibodies, and investigated the associations between environmental and genetic risk factors and variations in antibody responses.

Results: Healthy adults were more likely to mount IgG antibody responses to EBV proteins (median positivity frequency, 46.5% for IgG and 17.3% for IgA; P = 1.6 × 10-46, by the Wilcoxon rank sum test). Responses against glycoproteins were particularly prevalent. The correlations between antibody responses of the same class were higher than correlations across classes. The mucosal exposure to proteins involved in EBV reactivation (as determined by the IgA response) was associated with smoking (P = .002, by the sequence kernel association test-combined), and approximately one quarter of adults displayed antibody responses associated with EBV-related cancer risk.

Conclusions: These data comprehensively define the variability in human IgG and IgA antibody responses to the EBV proteome. Patterns observed can serve as the foundation for elucidating which individuals are at highest risk of EBV-associated clinical conditions and for identifying targets for effective immunodiagnostic tests.
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http://dx.doi.org/10.1093/infdis/jiy122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279144PMC
May 2018

Omega-3 decreases IL-6 levels in HIV and human herpesvirus-8 coinfected patients in Uganda.

AIDS 2018 02;32(4):505-512

Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Objective: Kaposi sarcoma is a HIV-associated malignancy caused by human herpesvirus-8 (HHV-8) that occurs at highest incidence in sub-Saharan Africa. Kaposi sarcoma patients often present with inflammatory symptoms associated with higher mortality.

Design: We conducted a double-blind, randomized, placebo-controlled study in Uganda to test whether omega-3 supplementation could reduce inflammation in HIV and HHV-8 coinfected adults. Patients with acute illness, AIDS, or advanced Kaposi sarcoma were ineligible, as were pregnant women. Participant IDs were pre-randomized, blocked by Kaposi sarcoma status, to either the omega-3 or placebo arm.

Methods: Omega-3 participants received a 3-g pill dose daily for 12 weeks (1.8-g eicosapentaenoic acid, 1.2-mg docosapentaenoic acid); placebo participants received 44.8 mg of high oleic safflower oil that appeared indistinguishable from the active supplement. Intervention effects were evaluated as the baseline-adjusted mean difference after 12 weeks between omega-3 and placebo participants in concentrations of fatty acids, inflammatory cytokines, and immune cells.

Results: The final study population included 56 Kaposi sarcoma patients and 11 Kaposi sarcoma-negative, HIV and HHV-8-positive participants randomized to receive either omega-3 (N = 33) or placebo (N = 34). Inflammatory cytokine IL-6 concentrations decreased in omega-3 participants (-0.78 pg/ml) but increased in placebo participants (+3.2 pg/ml; P = 0.04). We observed a trend toward decreased IL-6 after omega-3 supplementation specific to Kaposi sarcoma patients (P = 0.08). CD8 T-cell counts tended to increase in the omega-3 arm Kaposi sarcoma patients (+60 cells/μl), in contrast to decreases (-47 cells/μl) among placebo (P = 0.11).

Conclusion: Omega-3 supplementation decreased IL-6 concentrations among HIV and HHV-8 coinfected Ugandans, which may have clinical benefit for Kaposi sarcoma patients.
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http://dx.doi.org/10.1097/QAD.0000000000001722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872837PMC
February 2018

Cancer Risk in Older Persons Living With Human Immunodeficiency Virus Infection in the United States.

Clin Infect Dis 2018 06;67(1):50-57

Division of Cancer Epidemiology & Genetics, National Cancer Institute, Rockville, Maryland.

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.
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http://dx.doi.org/10.1093/cid/ciy012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248478PMC
June 2018

Identification of a Novel, EBV-Based Antibody Risk Stratification Signature for Early Detection of Nasopharyngeal Carcinoma in Taiwan.

Clin Cancer Res 2018 03 4;24(6):1305-1314. Epub 2018 Jan 4.

Queensland Institute of Medical Research, Brisbane, Australia.

Epstein-Barr virus (EBV) is necessary for the development of nasopharyngeal carcinoma (NPC). By adulthood, approximately 90% of individuals test EBV-positive, but only a fraction develop cancer. Factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective. We measured anti-EBV IgG and IgA antibody responses in 607 Taiwanese individuals. Antibodies were measured using a custom protein microarray targeting 199 sequences from 86 EBV proteins. Variation in response patterns between NPC cases and controls was used to develop an antibody-based risk score for predicting NPC. The overall accuracy [area under the curve (AUC)] of this risk score, and its performance relative to currently used biomarkers, was evaluated in two independent Taiwanese cohorts. Levels of 60 IgA and 73 IgG anti-EBV antibodies differed between stage I/IIa NPC cases and controls ( < 0.0002). Risk prediction analyses identified antibody targets that best discriminated NPC status-BXLF1, LF2,BZLF1, BRLF1, EAd, BGLF2, BPLF1, BFRF1, and BORF1. When combined with currently used VCA/EBNA1 IgA biomarkers, the resulting risk score predicted NPC with 93% accuracy (95% CI, 87%-98%) in the general Taiwanese population, a significant improvement beyond current biomarkers alone (82%; 95% CI, 75%-90%, ≤ 0.01). This EBV-based risk score also improved NPC prediction in genetically high-risk families (89%; 95% CI, 82%-96%) compared with current biomarkers (78%; 95% CI, 66%-90%, ≤ 0.03). We identified NPC-related differences in 133 anti-EBV antibodies and developed a risk score using this microarray dataset that targeted immune responses against EBV proteins from all stages of the viral life cycle, significantly improving the ability to predict NPC. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-1929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856605PMC
March 2018

Evaluation of nasal and nasopharyngeal swab collection for the detection of Epstein-Barr virus in nasopharyngeal carcinoma.

J Med Virol 2018 01 11;90(1):191-195. Epub 2017 Sep 11.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Epstein-Barr virus detection using nasopharyngeal swabs has been suggested as a potential screening test that could improve the specificity of current EBV-based serological assays. However, application requires insertion of the swab deep into the nasopharynx, a procedure not amenable to non-clinic screening. We reasoned that swabbing the more easily accessible nasal cavity might provide an appealing alternative for NPC detection. Patients > 18 years of age diagnosed with histologically confirmed NPC were recruited from the Otolaryngology Department at the National Taiwan University Hospital. ENT clinicians collected both nasal and nasopharyngeal swabs. EBV DNA and cellular beta-globulin DNA were quantified using quantitative PCR targeting a highly-conserved region of the BKRF1 gene. EBV DNA was detectable (non-zero) in all 34 nasopharyngeal swabs and above the positivity threshold of 1666 EBV copies in 30 (88.2%) patients. EBV DNA was detectable in 50% of 34 nasal swabs and above the positivity threshold in four (11.8%) patients. Average EBV DNA levels were >3-fold higher (P < 0.001) in nasopharyngeal compared to nasal swabs. Among the 17 NPC patients with detectable EBV DNA in both swab types, we observed correlation (P < 0.01) between EBV DNA measurements. Our data represent the first evaluation of EBV DNA collected from nasal swabs. Given current EBV DNA amplification techniques, nasopharyngeal swabs remain more sensitive than nasal swabs for NPC detection.
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http://dx.doi.org/10.1002/jmv.24918DOI Listing
January 2018

Excess Mortality among HIV-Infected Individuals with Cancer in the United States.

Cancer Epidemiol Biomarkers Prev 2017 07 15;26(7):1027-1033. Epub 2017 Jun 15.

Division of Cancer Epidemiology and Genetics, NCI, Rockville, Maryland.

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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http://dx.doi.org/10.1158/1055-9965.EPI-16-0964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500417PMC
July 2017

Survival Deficit for HIV-Infected Lymphoma Patients in the National Cancer Database.

Cancer Epidemiol Biomarkers Prev 2017 03;26(3):289-290

Division of Epidemiology, Albert Einstein College of Medicine, Bronx, New York.

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http://dx.doi.org/10.1158/1055-9965.EPI-17-0006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340270PMC
March 2017

Outcomes of cervical cancer among HIV-infected and HIV-uninfected women treated at the Brazilian National Institute of Cancer.

AIDS 2017 02;31(4):523-531

aPrograma de Oncovirologia, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil bDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA cSeção de Ginecologia Oncológica dPrograma de Carcinogênese Molecular ePrograma de Pesquisa Clínica, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil.

Objective: We assessed mortality, treatment response, and relapse among HIV-infected and HIV-uninfected women with cervical cancer in Rio de Janeiro, Brazil.

Design: Cohort study of 87 HIV-infected and 336 HIV-uninfected women with cervical cancer.

Methods: Patients at the Brazilian National Institute of Cancer (2001-2013) were matched on age, calendar year of diagnosis, clinical stage, and tumor histology. Staging and treatment with surgery, radiotherapy, and/or chemotherapy followed international guidelines. We used a Markov model to assess responses to initial therapy, and Cox models for mortality and relapse after complete response (CR).

Results: Among 234 deaths, most were from cancer (82% in HIV-infected vs. 93% in HIV-uninfected women); only 9% of HIV-infected women died from AIDS. HIV was not associated with mortality during initial follow-up but was associated more than 1-2 years after diagnosis [overall mortality: stage-adjusted hazard ratio 2.02, 95% confidence interval (CI) 1.27-3.22; cancer-specific mortality: 4.35, 1.86-10.2]. Among 222 patients treated with radiotherapy, HIV-infected had similar response rates to initial cancer therapy as HIV-uninfected women (hazard ratio 0.98, 95% CI 0.58-1.66). However, among women who were treated and had a CR, HIV was associated with elevated risk of subsequent relapse (hazard ratio 3.60, 95% CI 1.86-6.98, adjusted for clinical stage).

Conclusion: Among women with cervical cancer, HIV infection was not associated with initial treatment response or early mortality, but relapse after attaining a CR and late mortality were increased in those with HIV. These results point to a role for an intact immune system in control of residual tumor burden among treated cervical cancer patients.
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http://dx.doi.org/10.1097/QAD.0000000000001367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5263104PMC
February 2017

Birth order and risk of nasopharyngeal carcinoma in multiplex families from Taiwan.

Int J Cancer 2016 12 30;139(11):2467-73. Epub 2016 Aug 30.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, Maryland.

A small proportion of individuals infected with Epstein-Barr virus (EBV) develop nasopharyngeal carcinoma (NPC). Timing of initial exposure could alter immunological responses to primary EBV infection and explain variation in cancer risk later in life. We measured early life family structure as a proxy for the timing of primary EBV infection to examine whether earlier age at infection alters NPC risk. We utilized data from 480 NPC cases and 1,291 unaffected siblings from Taiwanese NPC multiplex families (≥ 2 family members with NPC, N = 2,921). Information on birth order within the family was derived from questionnaires. We utilized logistic regression models to examine the association between birth order and NPC, accounting for correlations between relatives. Within these high-risk families, older siblings had an elevated risk of NPC. Compared with being a first-born child, the risk (95% CIs) of NPC associated with a birth order of two, three, four and five or more was 1.00 (0.71, 1.40), 0.88 (0.62, 1.24), 0.74 (0.53, 1.05) and 0.60 (0.43, 0.82), respectively (P for trend = 0.002). We observed no associations between NPC risk and the number of younger siblings or cumulative infant-years exposure. These associations were not modified by underlying genetic predisposition or family size. We observed that early life family structure was important for NPC risk in NPC multiplex families, with older siblings having a greater risk of disease. Future studies focusing on more direct measures of the immune response to EBV in early childhood could elucidate the underlying mechanisms.
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http://dx.doi.org/10.1002/ijc.30390DOI Listing
December 2016

Changes in Clinical Context for Kaposi's Sarcoma and Non-Hodgkin Lymphoma Among People With HIV Infection in the United States.

J Clin Oncol 2016 09 9;34(27):3276-83. Epub 2016 Aug 9.

Elizabeth L. Yanik, Anna E. Coghill, and Eric A. Engels, National Cancer Institute, Rockville; Richard D. Moore, Johns Hopkins University, Baltimore, MD; Chad J. Achenbach, Northwestern University, Chicago, IL; Satish Gopal, Stephen R. Cole, and Joseph J. Eron, University of North Carolina at Chapel Hill, Chapel Hill, NC; W. Christopher Mathews, University of California, San Diego, San Diego, CA; Daniel R. Drozd, University of Washington, Seattle, WA; Ayad Hamdan, Beth Israel Deaconess Medical Center, Boston, MA; and Mary E. Ballestas, University of Alabama at Birmingham, Birmingham, AL.

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.
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http://dx.doi.org/10.1200/JCO.2016.67.6999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024548PMC
September 2016