Allan Hildesheim

National Cancer Institute (USA), Maryland, United States

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Publications (285)1815.17 Total impact

  • Leukemia. 01/2015;
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    ABSTRACT: Self-collected human papillomavirus (HPV) testing could reduce barriers to cervical cancer screening, with performance comparable to clinician-collected specimens. The ability of self-collected specimens to cross-sectionally and prospectively detect precursor lesions was investigated in an HPV vaccine randomized trial in Costa Rica. In the trial, 7466 women age 18 to 25 years received an HPV16/18 or control vaccine and were followed at least annually for four years. In this secondary analysis, we included all women who provided a self-collected cervicovaginal specimen six months after enrollment (5109 women = full analytical cohort). A subset (615 women = restricted cohort) also had clinician-collected specimens at the six-month postenrollment visit. High-grade squamous intraepithelial lesion or repeat low-grade squamous intraepithelial lesion prompted colposcopic referral throughout the study. HPV testing was performed with SPF10PCR/DEIA/LiPA25. Cross-sectional and prospective sensitivity, specificity, and predictive values were estimated. In the full cohort, one-time HPV testing on self-collected samples detected prevalent CIN2+ with a sensitivity of 88.7% (95% confidence interval [CI] =77.0% to 95.7%) and a specificity of 68.9% (95% CI = 67.6% to 70.1%). For predicting incident CIN2+ in the subsequent four years, sensitivity was 73.9% (95% CI = 65.8% to 81.0%) and specificity 69.4% (95% CI = 68.1% to 70.7%). In the restricted cohort, for incident CIN2+, self-collected HPV was much more sensitive than cytology (80.0% vs 10.0%); relative sensitivity was 0.1 (95% CI = 0.03% to 0.5%). Furthermore, three times more women with normal baseline cytology developed incident CIN2+ than those with negative self-collected HPV. Self-collected and clinician-collected HPV testing had comparable performance. Agreement between self- and clinician-collected samples was 89.7% (kappa = 0.78, McNemar χ2 = 0.62) for carcinogenic HPV types. Self-collected specimens can be used for HPV-based screening, providing sensitivity and specificity comparable with clinician-collected specimens and detecting disease earlier than cytology. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    JNCI Journal of the National Cancer Institute 01/2015; 107(1). · 15.16 Impact Factor
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    ABSTRACT: Objective Pro-inflammatory mechanisms may explain the increased ovarian cancer risk linked to more lifetime ovulations, endometriosis, and exposure to talc and asbestos, as well as decreased risk with non-steroidal anti-inflammatory drugs. Limited data are available to estimate ovarian cancer risk associated with levels of circulating inflammatory markers. Methods We conducted a nested case–control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Pre-diagnostic serum levels of 46 inflammation-related biomarkers (11 with a priori hypotheses; 35 agnostic) were measured in 149 incident ovarian cancer cases and 149 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression and adjusted for identified covariates. Results Increased ovarian cancer risk was associated with elevated levels of C-reactive protein (CRP) [tertile (T)3 vs. T1: OR (95% CI) 2.04 (1.06-3.93), p-trend = 0.03], interleukin (IL)-1α [detectable vs. undetectable: 2.23 (1.14-4.34)] and tumor necrosis factor alpha (TNF-α) [T3 vs. T1: 2.21 (1.06-4.63), p-trend = 0.04] Elevated IL-8 was non-significantly associated with risk [T3 vs. T1: 1.86 (0.96-3.61), p-trend = 0.05] In analyses restricted to serous ovarian cancer (n = 83), the associations with CRP and IL-8 remained or strengthened [CRP T3 vs. T1: 3.96 (1.14-11.14), p-trend = 0.008; IL-8 T3 vs. T1: 3.05 (1.09-8.51), p-trend = 0.03]. Elevated levels of CRP and TNF-α remained positively associated with ovarian cancer risk in analysis restricted to specimens collected at least 5 years before diagnosis (n = 56). Conclusion These results suggest that CRP, IL-1α, IL-8, and TNF-α are associated with increased risk of subsequently developing ovarian cancer.
    Cancer Epidemiology Biomarkers & Prevention 11/2014; · 4.32 Impact Factor
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    ABSTRACT: A comprehensive characterization of the effects of cigarette smoke on systemic soluble immune/inflammatory markers may provide insight into the mechanisms through which smoking causes disease.
    JNCI Journal of the National Cancer Institute 11/2014; 106(11). · 15.16 Impact Factor
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    ABSTRACT: Abstract The glutathione S-transferase (GST)-L1 multiplex serology assay has favorable properties for use in clinical trials and epidemiologic studies, including low cost, high throughput capacity, and low serum volume requirement. Therefore, we evaluated the GST-L1 assay as a measure of HPV16/18 vaccine immunogenicity. Our study population included 65 women selected from the Costa Rica Vaccine Trial who received the bivalent HPV16/18 virus-like particle (VLP) vaccine at the recommended 0/1/6-month schedule. We tested replicate serum samples from months 0/1/12 (i.e., after 0/1/3 doses) by GST-L1 and three other commonly used serology assays, VLP-ELISA, SEAP-NA, and cLIA. We calculated the percentage of women seropositive by GST-L1 by time point and HPV type (fourteen HPV types), and compared GST-L1 to other assays using Spearman rank correlation coefficients. After one vaccine dose, seropositivity by GST-L1 was 40% each for HPV16 and HPV18, increasing to 100% and 98%, respectively, after three doses. Seropositivity after three doses ranged from 32% to 69% for HPV types 31/33/45, for which partial vaccine efficacy is reported, though increases also occurred for types with no evidence for cross-protection (e.g., HPV77). GST-L1 correlated best after three doses with VLP-ELISA (HPV16 and HPV18 each ρ = 0.72) and SEAP-NA (HPV16 ρ = 0.65, HPV18 ρ = 0.71) (all p<0.001); correlation was lower with cLIA. The GST-L1 is suitable for evaluating HPV16/18 vaccine immunogenicity after three vaccine doses, although in contrast to other assays it may classify some samples as HPV16/18 seronegative. The assay's utility is limited for lower antibody levels such as after receipt of one dose.
    Human Vaccines and Therapeutics 10/2014; · 3.64 Impact Factor
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    ABSTRACT: Background: Epidemiologic studies examining circulating levels of inflammatory markers in relation to obesity and physical inactivity may aid in our understanding of the role of inflammation in obesity-related cancers. However, previous studies on this topic have focused on a limited set of markers. Methods: We evaluated associations between body mass index (BMI) and vigorous physical activity level, based on self-report, and serum levels of 78 inflammation-related markers. Markers were measured using a bead-based multiplex method among 1,703 men and women, ages 55-74 years and with no prior history of cancer at blood draw, selected for case-control studies nested within the Prostate, Lung, Ovarian, and Colorectal Cancer Screening Trial. Analyses were adjusted for age, sex, smoking, case-control study, physical activity, and BMI. Results: Twelve markers were positively associated with BMI after False Discovery Rate (FDR) correction. Odds ratios (ORs) and 95% confidence interval (CIs) for highest versus lowest levels of CCL2/MCP-1, CXCL5/ENA-78, sTNFR-II, CXCL10/IP-10, CXCL6/GCP2, CCL13/MCP-4, amylin, CRP, C-peptide, CCL19/MIP-3b, insulin, and leptin were 1.50 (1.14-1.98), 1.52 (1.12-2.05), 1.61 (1.17-2.20), 1.69 (1.25-2.28), 1.74 (1.24-2.44), 1.75 (1.22-2.50), 1.91 (1.31-2.78), 2.41 (1.36-4.25), 2.78 (1.83-4.24), 3.30 (2.28-4.78), 4.05 (2.51-6.55), 50.03 (19.87-125.99) per 5-kg/m2, respectively. Only CXCL12/SDF-1a was associated with physical activity (≥3 versus <1 hours/week; OR=3.28, 95% CI: 1.55-6.94) after FDR correction. Conclusions: BMI was associated with a wide range of circulating markers involved in the inflammatory response. Impact: This cross-sectional analysis identified serum markers could be considered in future studies aimed at understanding the underlying mechanisms linking inflammation with obesity and obesity-related cancers.
    Cancer Epidemiology Biomarkers & Prevention 09/2014; 23(12). · 4.32 Impact Factor
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    ABSTRACT: Background A community-based randomized trial was conducted in Costa Rica to evaluate the HPV-16/18 AS04-adjuvanted vaccine (NCT00128661). The primary objective was to evaluate efficacy of the vaccine to prevent cervical intraepithelial neoplasia 2 or more severe disease (CIN2+) associated with incident HPV-16/18 cervical infections. Secondary objectives were to evaluate efficacy against CIN2+ associated with incident cervical infection by any oncogenic HPVs and to evaluate duration of protection against incident cervical infection with HPV-16/18. Vaccine safety and immunogenicity over the 4-year follow-up were also evaluated. Methods We randomized (3727 HPV arm; 3739 control arm), vaccinated (HPV-16/18 or Hepatitis A) and followed (median 53.8 months) 7466 healthy women aged 18–25 years. 5312 women (2635 HPV arm; 2677 control arm) were included in the according to protocol analysis for efficacy. The full cohort was evaluated for safety. Immunogenicity was considered on a subset of 354 (HPV-16) and 379 (HPV-18) women. HPV type was assessed by PCR on cytology specimens. Immunogenicity was assessed using ELISA and inhibition enzyme immunoassays. Disease outcomes were histologically confirmed. Vaccine efficacy and 95% confidence intervals (95%CI) were computed. Results Vaccine efficacy was 89.8% (95% CI: 39.5–99.5; N = 11 events total) against HPV-16/18 associated CIN2+, 59.9% (95% CI: 20.7–80.8; N = 39 events total) against CIN2+ associated with non-HPV-16/18 oncogenic HPVs and 61.4% (95% CI: 29.5–79.8; N = 51 events total) against CIN2+ irrespective of HPV type. The vaccine had an acceptable safety profile and induced robust and long-lasting antibody responses. Conclusions Our findings confirm the high efficacy and immunogenicity of the HPV-16/18 vaccine against incident HPV infections and cervical disease associated with HPV-16/18 and other oncogenic HPV types. These results will serve as a benchmark to which we can compare future findings from ongoing extended follow-up of participants in the Costa Rica trial. Trial registration : Registered with clinicaltrials.gov: NCT00128661.
    Vaccine 09/2014; · 3.49 Impact Factor
  • Anna E Coghill, Allan Hildesheim
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    ABSTRACT: Epstein-Barr virus (EBV), a ubiquitous herpes virus that infects 90% of humans by adulthood, is linked to the development of various cancers, including nasopharyngeal carcinoma, gastric cancer, Burkitt lymphoma, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma. We reviewed the literature published since 1980 regarding an association between antibodies against EBV proteins and the risk of EBV-associated malignancies. Immunoglobulin A antibody levels that are elevated before diagnosis have consistently been associated with the risk of nasopharyngeal carcinoma, and patients with Hodgkin lymphoma have significantly higher immunoglobulin G antibody levels than disease-free controls. However, the link between the immune response to EBV and other EBV-associated malignancies was less clear. Although evidence of an association between the risk of Burkitt lymphoma and immunoglobulin G antibodies was consistent for available studies, the sample sizes were limited. Evidence for a link between antibodies against EBV and risk of either gastric cancer or NHL was inconsistent. Future investigations should account for tumor EBV status because only 7%-10% of gastric tumors and select NHL subtypes are related to EBV infection. Comparing differences in the associations between the humoral immune response to EBV and disease risk across cancers may help elucidate how this ubiquitous virus contributes to distinct tumors globally.
    American Journal of Epidemiology 08/2014; · 4.98 Impact Factor
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    ABSTRACT: Two trials of clinically approved human papillomavirus (HPV) vaccines, Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE I/II) and the Papilloma Trial Against Cancer in Young Adults (PATRICIA), reported a 22% difference in vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 2 or worse in HPV-naïve subcohorts; however, serological testing methods and the HPV DNA criteria used to define HPV-unexposed women differed between the studies. We applied previously described methods to simulate these HPV-naïve subcohorts within the Costa Rica HPV16/18 Vaccine Trial and assessed how these criteria affect the estimation of VE. We applied 2 enzyme-linked immunosorbent assay (ELISA) thresholds for HPV16 and HPV18 seropositivity (8 and 7 ELISA units/mL, respectively, for PATRICIA; 54 and 65 ELISA units/mL, respectively, for FUTURE I/II (to approximate the competitive Luminex immunoassay)) and 2 criteria for HPV DNA positivity (12 oncogenic HPV types, plus HPV66 and 68/73 for PATRICIA; or plus HPV6 and 11 for FUTURE I/II). VE was computed in the 2 naïve subcohorts. Using the FUTURE I/II and PATRICIA criteria, VE estimates against cervical intraepithelial neoplasia grade 2 or worse, regardless of HPV type, were 69.0% (95% confidence interval: 40.3%, 84.9%) and 80.8% (95% confidence interval: 52.6%, 93.5%), respectively (P = 0.1). Although the application of FUTURE I/II criteria to our cohort resulted in the inclusion of more sexually experienced women, methodological differences did not fully explain the VE differences.
    American journal of epidemiology. 08/2014;
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    ABSTRACT: Mathematical models of cervical cancer have been widely used to evaluate the comparative effectiveness and cost-effectiveness of preventive strategies. Major advances in the understanding of cervical carcinogenesis motivate the creation of a new disease paradigm in such models. To keep pace with the most recent evidence, we updated a previously developed microsimulation model of human papillomavirus (HPV) infection and cervical cancer to reflect 1) a shift towards health states based on HPV rather than poorly reproducible histological diagnoses and 2) HPV clearance and progression to precancer as a function of infection duration and genotype, as derived from the control arm of the Costa Rica Vaccine Trial (2004-2010). The model was calibrated leveraging empirical data from the New Mexico Surveillance, Epidemiology, and End Results Registry (1980-1999) and a state-of-the-art cervical cancer screening registry in New Mexico (2007-2009). The calibrated model had good correspondence with data on genotype- and age-specific HPV prevalence, genotype frequency in precancer and cancer, and age-specific cancer incidence. We present this model in response to a call for new natural history models of cervical cancer intended for decision analysis and economic evaluation at a time when global cervical cancer prevention policy continues to evolve and evidence of the long-term health effects of cervical interventions remains critical.
    American Journal of Epidemiology 07/2014; · 4.98 Impact Factor
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    The Journal of infectious diseases. 06/2014;
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    ABSTRACT: Background: Associations between human leukocyte antigens (HLA) alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC), the major histologic subtype. We evaluated the association between HLA class I (A, B, and C) and class II (DRB1 and DQB1) loci and risk of cervical adenocarcinoma (ADC), a less common but aggressive histologic subtype. Methods: We pooled data from the Eastern and Western US Cervical Cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n = 630 ADC; n = 775 controls). Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type) and 38 non a priori common alleles, as odds ratios (OR) and 95% confidence intervals (CI), adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls. Results: Three of the a priori alleles were significantly associated with decreased risk of ADC [DRB1*13:01 (OR = 0.61; 95% CI: 0.41-0.93), DRB1*13:02 (OR = 0.49; 95% CI: 0.31-0.77), and DQB1*06:03 (OR = 0.64; 95% CI: 0.42-0.95)]; one was associated with increased risk [B*07:02 (OR = 1.39; 95% CI: 1.07-1.79)]. Among alleles not previously reported, DQB1*06:04 (OR = 0.46; 95% CI: 0.27-0.78) was associated with decreased risk of ADC and remained significant after correction for multiple comparisons, and C*07:02 (OR = 1.41; 95% CI: 1.09-1.81) was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR = 1.33; 95% CI: 1.01-1.76) and decreased risk with DRB1*13:02/DQB1*06:04 (OR = 0.41; 95% CI: 0.21-0.80). Conclusion: Results suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18-related tumors, consistent with the hypothesis that HLA recognition is HPV type-specific.
    Frontiers in Oncology 06/2014; 4:119.
  • JAMA The Journal of the American Medical Association 06/2014; 311(23):2439. · 30.39 Impact Factor
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    ABSTRACT: There is a well-established connection between immune status and carcinogenesis, as an increased risk of cancer has been associated with a history of immunosuppressive medication use, with certain chronic infections such as HIV, and with certain autoimmune diseases and lifestyle factors which result in chronic immune alterations and abnormalities. Furthermore, more subtle changes in immune functioning, including imbalances in Th1/Th2 responses resulting from cytokine alterations, have been implicated in the oncogenic process via regulation of transcriptional factors and of tumor growth, angiogenesis, and cell differentiation and survival. Occupational exposures such as trichloroethylene (TCE) are hypothesized to increase cancer risk partly through immunological mechanisms. Characterizing the relationship between occupational chemical exposures and various immune markers could provide important insights into the link between occupational exposures, immunological responses to such exposures and subsequent cancer risk.
    Occupational and Environmental Medicine 06/2014; 71 Suppl 1:A125. · 3.23 Impact Factor
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    ABSTRACT: To assess the association between occupational exposure to carbon nanotubes (CNTs) and early immunological and cardiovascular health effects.
    Occupational and Environmental Medicine 06/2014; 71 Suppl 1:A35. · 3.23 Impact Factor
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    ABSTRACT: Background:Nasopharyngeal carcinoma (NPC) is an EBV associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of ~90%. However, NPC is typically diagnosed at advanced stages, where disease-free survival is <50%. There is therefore a need for clinical tools to assist in early NPC detection, particularly in high-risk individuals. Methods:We evaluated the ability of anti-EBV IgA antibodies to detect incident NPC among high-risk Taiwanese individuals. NPC cases (N=21) and age and sex-matched controls (N=84) were selected. Serum collected prior to NPC diagnosis was tested for ELISA-based IgA markers against the following EBV peptides: EBNA1, VCAp18, EAp138, Ead_p47, and VCAp18 + EBNA1 peptide mixture. The sensitivity, specificity, and screening program parameters were calculated. Results:EBNA1 IgA had the best performance characteristics. At an optimized threshold value, EBNA1 IgA measured at baseline identified 80% of the high-risk individuals who developed NPC during follow-up (80% sensitivity). However, approximately 40% of high-risk individuals who did not develop NPC also tested positive (false positives). Application of EBNA1 IgA as a biomarker to detect incident NPC in a previously unscreened, high-risk population revealed that 164 individuals needed to be screened to detect 1 NPC and that 69 individuals tested positive per case detected. Conclusions:EBNA1 IgA proved to be a sensitive biomarker for identifying incident NPC, but future work is warranted to develop more specific screening tools to decrease the number of false positives. Impact:Results from this study could inform decisions regarding screening biomarkers and referral thresholds for future NPC early-detection program evaluations.
    Cancer Epidemiology Biomarkers & Prevention 04/2014; · 4.56 Impact Factor
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    ABSTRACT: Several assays are used to measure type-specific serological responses to human papillomavirus (HPV), including the bead-based glutathione S-transferase (GST)-L1 multiplex serology assay and virus-like particle (VLP)-based ELISA. We evaluated the high-throughput GST-L1, which is increasingly used in epidemiologic research, as a measure of cumulative HPV infection and future immune protection among HPV-unvaccinated women. We tested enrollment sera from participants in the control arm of the Costa Rica Vaccine Trial (n = 488) for HPV16 and HPV18 using GST-L1, VLP-ELISA, and two assays that measure neutralizing antibodies (cLIA and SEAP-NA). With statistical adjustment for sampling, we compared GST-L1 serostatus to established HPV seropositivity correlates and incident cervical HPV infection using odds ratios. We further compared GST-L1 to VLP-ELISA using pair-wise agreement statistics and by defining alternate assay cutoffs. Odds of HPV16 GST-L1 seropositivity increased with enrollment age (OR = 1.20 per year, 95%CI 1.03-1.40) and lifetime number of sexual partners (OR = 2.06 per partner, 95%CI 1.49-2.83), with similar results for HPV18. GST-L1 seropositivity did not indicate protection from incident infection over 4 years of follow-up (HPV16 adjusted OR = 1.72, 95%CI 0.95-3.13; HPV18 adjusted OR = 0.38, 95%CI 0.12-1.23). Seroprevalence by GST-L1 (HPV16 and HPV18, respectively) was 5.0% and 5.2%, compared to 19.4% and 23.8% by VLP-ELISA, giving positive agreement of 39.2% and 20.8%. Lowering GST-L1 seropositivity cutoffs improved GST-L1/VLP-ELISA positive agreement to 68.6% (HPV16) and 61.5% (HPV18). Our data support GST-L1 as a marker of cumulative HPV infection, but not immune protection. At lower seropositivity cutoffs, GST-L1 better approximates VLP-ELISA.
    BMC Infectious Diseases 03/2014; 14(1):120. · 2.56 Impact Factor
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    ABSTRACT: Background: Different assays, including the competitive Luminex immunoassay (cLIA), secreted alkaline phosphatase neutralization assay (SEAP-NA), and virus-like particle-based ELISA, are commonly used to measure antibody responses after human papillomavirus (HPV) vaccination. Direct assay comparisons aid interpretation of immunogenicity data evaluated by different assays. Methods: We compared cLIA to SEAP-NA and ELISA among 51 HPV16/18-vaccinated women enrolled in the Costa Rica Vaccine Trial. We tested replicate serum samples collected at months 0, 1, and 12 by HPV16/18 cLIA, SEAP-NA, and ELISA. For a subset (N = 10), we further tested month 6, 24 and 36 samples. We calculated seroprevalence estimates and Spearman rank correlation coefficients comparing cLIA to SEAP-NA and ELISA. Results: After one vaccine dose, seroprevalence by SEAP-NA and ELISA was 100% (both HPV16 and HPV18), and by cLIA was 96% (95% CI 87-100%) for HPV16 and 71% (95% CI 56-83%) for HPV18. Seroprevalence was 100% by all assays after three doses. Correlation between assays was high after one vaccine dose [cLIA/SEAP-NA ρ = 0.91 (HPV16) and ρ = 0.86 (HPV18); cLIA/ELISA ρ = 0.84 (HPV16) and ρ = 0.74 (HPV18); all p < 0.001] and remained high through month 36. Ratios of mean antibody levels to seropositivity cutoffs at month 36 were lower for cLIA than for SEAP-NA or ELISA, particularly for HPV18 (HPV18 ratio for cLIA 1.9, SEAP-NA 3.5, ELISA 3.4). Conclusion: Though correlation between cLIA and SEAP-NA/ELISA is high and stable after vaccination, the assays differ in scale and sensitivity, with notable differences after one vaccine dose and for HPV18. Our results demonstrate that comparisons of antibody responses to HPV vaccination measured by different assays are approximate, and must consider biological and technical differences between assays.
    Frontiers in Oncology 01/2014; 3:328.
  • Journal of Clinical Oncology 12/2013; · 17.88 Impact Factor
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    ABSTRACT: Despite growing recognition of an etiologic role for inflammation in lung carcinogenesis, few prospective epidemiologic studies have comprehensively investigated the association of circulating inflammation markers with lung cancer. We conducted a nested case-control study (n = 526 lung cancer patients and n = 592 control subjects) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Control subjects were matched to lung cancer case patients on age, sex, follow-up time (median = 2.9 years), randomization year, and smoking (pack-years and time since quitting). Serum levels of 77 inflammation markers were measured using a Luminex bead-based assay. Conditional logistic regression and weighted Cox models were used to estimate odds ratios (ORs) and cumulative risks, respectively. Of 68 evaluable markers, 11 were statistically significantly associated with lung cancer risk (P trend across marker categories < .05), including acute-phase proteins (C-reactive protein [CRP], serum amyloid A [SAA]), proinflammatory cytokines (soluble tumor necrosis factor receptor 2 [sTNFRII]), anti-inflammatory cytokines (interleukin 1 receptor antagonist [IL-1RA]), lymphoid differentiation cytokines (interleukin 7 [IL-7]), growth factors (transforming growth factor alpha [TGF-A]), and chemokines (epithelial neutrophil-activating peptide 78 [ENA 78/CXCL5], monokine induced by gamma interferon [MIG/CXCL9], B cell-attracting chemokine 1 [BCA-1/CXCL13], thymus activation regulated chemokine [TARC/CCL17], macrophage-derived chemokine [MDC/CCL22]). Elevated marker levels were associated with increased lung cancer risk, with odds ratios comparing the highest vs the lowest group ranging from 1.47 (IL-7) to 2.27 (CRP). For IL-1RA, elevated levels were associated with decreased lung cancer risk (OR = 0.71; 95% confidence interval = 0.51 to 1.00). Associations did not differ by smoking, lung cancer histology, or latency. A cross-validated inflammation score using four independent markers (CRP, BCA-1/CXCL13, MDC/CCL22, and IL-1RA) provided good separation in 10-year lung cancer cumulative risks among former smokers (quartile [Q] 1 = 1.1% vs Q4 = 3.1%) and current smokers (Q1 = 2.3% vs Q4 = 7.9%) even after adjustment for smoking. Some circulating inflammation marker levels are associated with prospective lung cancer risk.
    CancerSpectrum Knowledge Environment 11/2013; · 14.07 Impact Factor

Publication Stats

13k Citations
1,815.17 Total Impact Points

Institutions

  • 1990–2014
    • National Cancer Institute (USA)
      • • Division of Cancer Epidemiology and Genetics
      • • Infections and Immunoepidemiology
      • • Hormonal and Reproductive Epidemiology
      • • Occupational and Environmental Epidemiology
      • • Epidemiology and Biostatistics
      Maryland, United States
    • National Institutes of Health
      • • Division of Cancer Epidemiology and Genetics
      • • Laboratory of Cellular Oncology
      • • Branch of Occupational and Environmental Epidemiology
      Maryland, United States
    • Mario Negri Institute for Pharmacological Research
      • Department of Epidemiology
      Milano, Lombardy, Italy
  • 2012
    • Leidos Biomedical Research
      Maryland, United States
  • 2007–2012
    • DDL Diagnostic Laboratory
      Rijswijk, South Holland, Netherlands
    • Johns Hopkins Bloomberg School of Public Health
      • Department of Epidemiology
      Baltimore, MD, United States
    • Radboud University Nijmegen
      Nymegen, Gelderland, Netherlands
  • 2003–2012
    • NCI-Frederick
      Maryland, United States
    • Albert Einstein College of Medicine
      • Department of Pediatrics
      New York City, NY, United States
    • Pontifical Catholic University of Chile
      • Departamento de Salud Pública
      Santiago, Region Metropolitana de Santiago, Chile
  • 2011
    • Costa Rican Institute for Research and Education on Nutrition and Health
      La Unión, Cartago, Costa Rica
    • Harvard University
      • Center for Health Decision Science
      Boston, MA, United States
  • 2010
    • City of Hope National Medical Center
      Duarte, California, United States
  • 2005
    • Universidade Federal do Rio Grande do Sul
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil
  • 2004
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2001
    • Georgetown University
      • Lombardi Cancer Center
      Washington, Washington, D.C., United States
    • University of Pittsburgh
      • Department of Epidemiology
      Pittsburgh, PA, United States
  • 2000
    • Kaiser Permanente
      • Department of Pathology
      Oakland, California, United States
  • 1999
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
    • Brown University
      Providence, Rhode Island, United States
    • National Taiwan University
      • Graduate Institute of Epidemiology and Preventive Medicine
      Taipei, Taipei, Taiwan
    • Dartmouth College
      Hanover, New Hampshire, United States
    • Uniformed Services University of the Health Sciences
      • Department of Preventive Medicine & Biometrics
      Bethesda, MD, United States
  • 1998
    • Johns Hopkins Medicine
      • Department of Pathology
      Baltimore, MD, United States
  • 1997
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
  • 1996
    • University of New Mexico Hospitals
      Albuquerque, New Mexico, United States