Allan Hildesheim

Northern Inyo Hospital, BIH, California, United States

Are you Allan Hildesheim?

Claim your profile

Publications (314)2102.15 Total impact

  • JNCI Journal of the National Cancer Institute 01/2016; 108(1):djv302. DOI:10.1093/jnci/djv302 · 12.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Identification of human papillomavirus (HPV) DNA in cervical tissue is important for understanding cervical carcinogenesis and for evaluating cervical cancer prevention approaches. However, HPV genotyping using formalin-fixed, paraffin-embedded (FFPE) tissues is technically challenging. We evaluated the performance of four commonly used genotyping methods on FFPE cervical specimens conducted in different laboratories and compared to genotyping results from cytological samples. Methods: We included 60 pairs of exfoliated-cell and FFPE specimens from women with histologically confirmed cervical intraepithelial lesions grade 2 or 3. Cytology specimens were genotyped using the Linear Array assay. Four expert laboratories processed tissue specimens using different preparation methods and then genotyped the resultant sample preparations using four different HPV genotyping methods: SPF10-PCR DEIA LiPA25 (version 1), Inno-LiPA, Linear Array and the Onclarity assay. Percentage agreement, kappa statistics and McNemar's chi-square were calculated for each comparison of different methods and specimen types. Results: Overall agreement with respect to carcinogenic HPV status for FFPE samples between different methods was: 81.7, 86.7 and 91.7 % for Onclarity versus Inno-LiPA, Linear Array and SPF-LiPA25, respectively; 81.7 and 85.0 % for Linear Array versus Inno-LiPA and SPF-LiPA25, respectively; and 86.7 % for SPF-LiPA25 versus Inno-LiPA. Type-specific agreement was >88.3 % for all pair-wise comparisons. Comparisons with cytology specimens resulted in overall agreements from 80 to 95 % depending on the method and type-specific agreement was >90 % for most comparisons. Conclusions: Our data demonstrate that the four genotyping methods run by expert laboratories reliably detect HPV DNA in FFPE specimens with some variation in genotype-specific detection.
    BMC Infectious Diseases 11/2015; 15(1):544. DOI:10.1186/s12879-015-1281-5 · 2.61 Impact Factor

  • Cancer Epidemiology Biomarkers & Prevention 11/2015; DOI:10.1158/1055-9965.EPI-15-0144 · 4.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Results from the Costa Rica Vaccine Trial (CVT) using the bivalent HPV16/18 vaccine demonstrated partial cross-protection against HPV31, 33, 45, and increased HPV51 incidence. Methods: A study nested within the CVT intention-to-treat cohort was designed to assess high-risk (HR)-HPV variant lineage-specific vaccine efficacy (VE). The two main endpoints were (i) long-term incident infections persisting ≥2 years and/or progression to HSIL (CIN2-3), and (ii) incident transient infections lasting <2 years. For efficiency, incident infections by HPV types 16, 18, 31, 33, 35, 45 and 51 resulting in persistence/CIN2-3 were matched (1:2) to the more frequent transient viral infections by type. Variant lineages were determined by sequencing the URR and/or E6 regions. Results: VE's against persistent or transient infections with HPV16, 18, 33, 35, 45 and 51 did not differ significantly by variant lineage. As the possible exception, VE's against persistence/CIN2-3 with HPV31 A/B and HPV31C variants were -7.1% (95% CI: -33.9% to 0%) and 86.4% (95%CI: 65.1% to 97.1%), respectively (p=0.02 for test of equal VE). No difference in VE was observed by variant among transient HPV31 infections (p=0.68). Conclusions: Overall, sequence variation at the variant level does not appear to explain partial HPV vaccine cross-protection.
    The Journal of Infectious Diseases 10/2015; DOI:10.1093/infdis/jiv519 · 6.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We conducted two independent nested case-control studies to identify circulating inflammation markers reproducibly associated with lung cancer risk and to investigate the utility of replicated markers for lung cancer risk stratification. Nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the previously published discovery study included 526 lung cancer patients and 592 control subjects and the replication study included 526 lung cancer case patients and 625 control subjects. Control subjects were matched by sex, age, smoking, study visit, and years of blood draw and exit. Serum levels of 51 inflammation markers were measured. Odds ratios (ORs) were estimated with conditional logistic regression. All statistical tests were two-sided. Of 11 markers identified in the discovery study, C-reactive protein (CRP) (odds ratio [OR] [highest vs. lowest category] = 1.77, 95% confidence interval [CI] = 1.23 to 2.54), serum amyloid A (SAA) (OR = 1.88, 95% CI = 1.28 to 2.76), soluble tumor necrosis factor receptor-2 (sTNFRII) (OR = 1.70, 95% CI = 1.18 to 2.45), and monokine induced by gamma interferon (CXCL9/MIG) (OR = 2.09, 95% CI = 1.41 to 3.00) were associated with lung cancer risk in the replication study (P trend < .01). In pooled analyses, CRP, SAA, and CXCL9/MIG remained associated with lung cancer more than six years before diagnosis (P trend < .05). The incorporation of an inflammation score combining these four markers did not improve the sensitivity (77.6% vs 75.8%, P = .33) or specificity (56.1% vs 56.1%, P = .98) of risk-based lung cancer models. Circulating levels of CRP, SAA, sTNFRII, and CXCL9/MIG were reproducibly associated with lung cancer risk in two independent studies within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, underscoring an etiologic role for inflammation in lung carcinogenesis, though replication is needed in other populations. Markers did not improve lung cancer risk stratification beyond standard demographic and behavioral characteristics. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
    Journal of the National Cancer Institute 10/2015; 107(10). DOI:10.1093/jnci/djv199 · 12.58 Impact Factor

  • The Lancet Oncology 09/2015; 16(9):e424-5. DOI:10.1016/S1470-2045(15)00196-5 · 24.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To examine the effect of the bivalent human papillomavirus (HPV) vaccine on miscarriage. Design: Observational long term follow-up of a randomized, double blinded trial combined with an independent unvaccinated population based cohort. Setting: Single center study in Costa Rica. Participants: 7466 women in the trial and 2836 women in the unvaccinated cohort enrolled at the end of the randomized trial and in parallel with the observational trial component. Intervention: Women in the trial were assigned to receive three doses of bivalent HPV vaccine (n=3727) or the control hepatitis A vaccine (n=3739). Crossover bivalent HPV vaccination occurred in the hepatitis A vaccine arm at the end of the trial. Women in the unvaccinated cohort received (n=2836) no vaccination. Main outcome measure: Risk of miscarriage, defined by the US Centers for Disease Control and Prevention as fetal loss within 20 weeks of gestation, in pregnancies exposed to bivalent HPV vaccination in less than 90 days and any time from vaccination compared with pregnancies exposed to hepatitis A vaccine and pregnancies in the unvaccinated cohort. Results: Of 3394 pregnancies conceived at any time since bivalent HPV vaccination, 381 pregnancies were conceived less than 90 days from vaccination. Unexposed pregnancies comprised 2507 pregnancies conceived after hepatitis A vaccination and 720 conceived in the unvaccinated cohort. Miscarriages occurred in 451 (13.3%) of all exposed pregnancies, in 50 (13.1%) of the pregnancies conceived less than 90 days from bivalent HPV vaccination, and in 414 (12.8%) of the unexposed pregnancies, of which 316 (12.6%) were in the hepatitis A vaccine group and 98 (13.6%) in the unvaccinated cohort. The relative risk of miscarriage for pregnancies conceived less than 90 days from vaccination compared with all unexposed pregnancies was 1.02 (95% confidence interval 0.78 to 1.34, one sided P=0.436) in unadjusted analyses. Results were similar after adjusting for age at vaccination (relative risk 1.15, one sided P=0.17), age at conception (1.03, P=0.422), and calendar year (1.06, P=0.358), and in stratified analyses. Among pregnancies conceived at any time from bivalent HPV vaccination, exposure was not associated with an increased risk of miscarriage overall or in subgroups, except for miscarriages at weeks 13-20 of gestation (relative risk 1.35, 95% confidence interval 1.02 to 1.77, one sided P=0.017). Conclusions: There is no evidence that bivalent HPV vaccination affects the risk of miscarriage for pregnancies conceived less than 90 days from vaccination. The increased risk estimate for miscarriages in a subgroup of pregnancies conceived any time after vaccination may be an artifact of a thorough set of sensitivity analyses, but since a genuine association cannot totally be ruled out, this signal should nevertheless be explored further in existing and future studies.Trial registration NCT00128661 and NCT01086709.
    BMJ (online) 09/2015; 351:h4358. DOI:10.1136/bmj.h4358 · 17.45 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):4680-4680. DOI:10.1158/1538-7445.AM2015-4680 · 9.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic inflammation is recognized to play a role in the development of several cancers. Past investigations of inflammation and cancer have typically been small, used varied assay platforms, and included a narrow range of analytes. Multiplex technologies have now been developed to measure larger numbers of inflammatory markers using small volumes of specimens. This has created an opportunity for systematic, large-scale epidemiological studies to evaluate the role of inflammation in cancer. However, lack of consensus on the approach to these studies, the technologies/assays to be used, and the most adequate analysis/interpretation of findings have thus far hindered progress. In June of 2014, the National Cancer Institute convened a workshop involving epidemiologists, immunologists, statisticians, and laboratory biologists to share their experiences with new inflammation marker technologies and findings from association studies using such methods and technologies ( Consensus and gaps in our understanding of the role of chronic inflammation in cancer were identified and recommendations made to improve future efforts in this area. These recommendations are summarized herein, along with specific suggestions for how they may be implemented. By facilitating discussions among various groups, and encouraging interdisciplinary collaborations, we anticipate that the pace of research in this field will be accelerated and duplication of efforts can be minimized. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 06/2015; 24(9). DOI:10.1158/1055-9965.EPI-14-1419 · 4.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Coffee drinking has been inversely associated with mortality as well as cancers of the endometrium, colon, skin, prostate, and liver. Improved insulin sensitivity and reduced inflammation are among the hypothesized mechanisms by which coffee drinking may affect cancer risk; however, associations between coffee drinking and systemic levels of immune and inflammatory markers have not been well characterized. We used Luminex bead-based assays to measure serum levels of 77 immune and inflammatory markers in 1,728 older non-Hispanic Whites. Usual coffee intake was self-reported using a food frequency questionnaire. We used weighted multivariable logistic regression models to examine associations between coffee and dichotomized marker levels. We conducted statistical trend tests by modeling the median value of each coffee category and applied a 20% false discovery rate criterion to P-values. Ten of the 77 markers were nominally associated (P-value for trend<0.05) with coffee drinking. Five markers withstood correction for multiple comparisons and included aspects of the host response namely chemotaxis of monocytes/macrophages (IFNγ, CX3CL1/fractalkine, CCL4/MIP-1β), pro-inflammatory cytokines (sTNFRII) and regulators of cell growth (FGF-2). Heavy coffee drinkers had lower circulating levels of IFNγ (OR=0.35; 95% CI 0.16-0.75), CX3CL1/fractalkine (OR=0.25; 95% CI 0.10-0.64), CCL4/MIP-1β (OR=0.48; 95% CI 0.24-0.99), FGF-2 (OR=0.62; 95% CI 0.28-1.38), and sTNFRII (OR=0.34; 95% CI 0.15-0.79) than non-coffee drinkers. Lower circulating levels of inflammatory markers among coffee drinkers may partially mediate previously observed associations of coffee with cancer and other chronic diseases. Validation studies, ideally controlled feeding trials, are needed to confirm these associations. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 05/2015; 24(7). DOI:10.1158/1055-9965.EPI-15-0038-T · 4.13 Impact Factor
  • Dr Douglas R Lowy · Rolando Herrero · Allan Hildesheim ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Although available human papillomavirus (HPV) vaccines have high efficacy against incident infection and disease caused by HPV types that they specifically target, new vaccine trials continue to be needed. The goals of these trials could include change of vaccine dose or route of administration (or both), development of second-generation vaccines, and the regional manufacture of biosimilar vaccines. We summarise present thinking about primary endpoints for HPV vaccine trials as developed at an experts workshop convened by the International Agency for Research on Cancer and the US National Cancer Institute in September, 2013. Efficacy trials that have led to licensure for cervical cancer prevention have used the disease endpoint of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). However, on the basis of experience from the trials and present knowledge of HPV infection, future efficacy trials for new vaccines can be safely streamlined by the use of persistent HPV infection, which occurs more frequently than CIN2+, and can be more reproducibly measured as a primary endpoint. Immunobridging trials can be sufficient to ascertain immunological non-inferiority for licensure for alternate dosing schedules, bridging to age 26 years or younger, and biosimilar vaccines, with post-licensure surveillance confirming effectiveness. These recommendations are intended to help stimulate continued vaccine development while ensuring appropriate assessment of safety and efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 05/2015; 16(5):e226-e233. DOI:10.1016/S1470-2045(15)70075-6 · 24.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Formaldehyde has been proposed to be a human myeloid leukemogen. However, the mechanistic basis for this association is still debated. We aimed to evaluate whether circulating immune/inflammation markers were altered in workers occupationally exposed to formaldehyde. Using a multiplexed bead-based assay, we measured serum levels of 38 immune/inflammation markers in a cross-sectional study of 43 formaldehyde-exposed and 51 unexposed factory workers in Guangdong, China. Linear regression models adjusting for potential confounders were used to compare marker levels in exposed and unexposed workers. We found significantly lower circulating levels of two markers among exposed factory workers compared to unexposed controls that remained significant after adjusting for potential confounders and multiple comparisons using a false discovery rate (FDR) of 10%, including chemokine (C-X-C motif) ligand 11 (CXCL11; 36.2 pg/ml in exposed versus 48.4 pg/ml in controls, P=0.0008) and thymus and activation regulated chemokine (TARC; 52.7 pg/ml in exposed versus 75.0 pg/ml in controls, P=0.0028), suggesting immunosuppression among formaldehyde-exposed workers. Our findings are consistent with recently emerging understanding that immunosuppression might be associated with myeloid diseases. These findings, if replicated in a larger study, may provide insights into the mechanisms by which formaldehyde promotes leukemogenesis. Published by Oxford University Press 2015.
    Carcinogenesis 04/2015; 75(15 Supplement). DOI:10.1093/carcin/bgv055 · 5.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Costa Rica Vaccine Trial (CVT) was a randomized clinical trial conducted between 2004 and 2010, which randomized 7466 women aged 18 to 25 to receive the bivalent HPV-16/18 vaccine or control Hepatitis-A vaccine. Participants were followed for 4 years with cross-over vaccination at the study end. In 2010 the long term follow-up (LTFU) study was initiated to evaluate the 10-year impact of HPV-16/18 vaccination, determinants of the immune response, and HPV natural history in a vaccinated population. Herein, the rationale, design and methods of the LTFU study are described, which actively follows CVT participants in the HPV-arm 6 additional years at biennial intervals (3 additional study visits for 10 years of total follow-up), or more often if clinically indicated. According to the initial commitment, women in the Hepatitis-A arm were offered HPV vaccination at cross-over; they were followed 2 additional years and exited from the study. 92% of eligible CVT women accepted participation in LTFU. To provide underlying rates of HPV acquisition and cervical disease among unvaccinated women to compare with the HPV-arm during LTFU, a new unvaccinated control group (UCG) of women who are beyond the age generally recommended for routine vaccination was enrolled, and will be followed by cervical cancer screening over 6 years. To form the UCG, 5000 women were selected from a local census, of whom 2836 women (61% of eligible women) agreed to participate. Over 90% of participants complied with an interview, blood and cervical specimen collection. Evaluation of comparability between the original (Hepatitis-A arm of CVT) and new (UCG) control groups showed that women's characteristics, as well as their predicted future risk for cervical HPV acquisition, were similar, thus validating use of the UCG. LTFU is poised to comprehensively address many important questions related to long-term effects of prophylactic HPV vaccines. Copyright © 2015. Published by Elsevier Ltd.
    Vaccine 03/2015; 33(18). DOI:10.1016/j.vaccine.2015.03.015 · 3.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Gallbladder disease is highly related to inflammation, but the inflammatory processes are not well understood. Bile provides a direct substrate in assessing the local inflammatory response that develops in the gallbladder. To assess the reproducibility of measuring inflammatory markers in bile, we designed a methods study of 69 multiplexed immune-related markers measured in bile obtained from gallstone patients. To evaluate assay performance, a total of 18 bile samples were tested twice within the same plate for each analyte, and the 18 bile samples were tested on two different days for each analyte. We used the following performance parameters: detectability, coefficient of variation (CV), intraclass correlation coefficient (ICC), and percent agreement (concordance among replicate measures above and below detection limit). Furthermore, we examined the association of analyte levels with gallstone characteristics such as type, numbers, and size. All but 3 analytes (Stem Cell Factor, SCF; Thrombopoietin, TPO; sIL-1RI) were detectable in bile. 52 of 69 (75.4%) analytes had detectable levels for at least 50% of the subjects tested. The within-plate CVs were ⩽25% for 53 of 66 (80.3%) detectable analytes, and across-plate CVs were ⩽25% for 32 of 66 (48.5%) detectable analytes. Moreover, 64 of 66 (97.0%) analytes had ICC values of at least 0.8. Lastly, the percent agreement was high between replicates for all of the analytes (median; within plate, 97.2%; across plate, 97.2%). In exploratory analyses, we assessed analyte levels by gallstone characteristics and found that levels for several analytes decreased with increasing size of the largest gallstone per patient. Our data suggest that multiplex assays can be used to reliably measure cytokines and chemokines in bile. In addition, gallstone size was inversely related to the levels of select analytes, which may aid in identifying critical pathways and mechanisms associated with the pathogenesis of gallbladder diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Cytokine 03/2015; 73(1):84-90. DOI:10.1016/j.cyto.2015.01.033 · 2.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:Regular aspirin use may decrease cancer risk by reducing chronic inflammation. However, associations between aspirin use and circulating markers of inflammation have not been well-studied. Methods: Serum levels of 78 inflammatory markers were measured in 1,819 55-74 year-old men and women in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Data were combined from 3 completed case-control studies and re-weighted to the PLCO screening arm. Self-reported aspirin and ibuprofen use (number of tablets taken per day/week/month) over the previous 12 months was collected at baseline. Associations between i) non-regular (<4 tablets/month), ii) low (1-4 tablets/week), iii) moderate (1 tablet/day) or iv) high (2+ tablets/day) regular aspirin or ibuprofen use and marker levels were assessed with weighted logistic regression. Results: Aspirin use was nominally associated with (ptrend across categories≤0.05) decreased levels of chemokine C-C motif ligand 15 (CCL15) (OR 0.5; 95%CI: 0.3-0.8; moderate versus non-regular use); soluble vascular endothelial growth factor receptor 2 (sVEGFR2) (OR 0.7; 95%CI: 0.4-1.0); soluble tumor necrosis factor receptor 1 (sTNFR1) (OR 0.6; 95%CI: 0.4-0.9) and increased levels of CCL13 (OR 1.3; 95%CI: 0.8-2.1); CCL17 (OR 1.1; 95%CI: 0.7-1.9) and interleukin 4 (IL-4) (OR 1.6; 95%CI: 0.9-2.8). Trends were not statistically significant following correction for multiple comparisons. Likewise, no statistically significant associations were observed between ibuprofen use and marker levels. Conclusions: No significant associations were observed between regular aspirin use and the inflammatory markers assessed. Impact: Additional studies are needed to better understand the relationship between aspirin use, chronic inflammation and cancer risk. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 02/2015; 24(5). DOI:10.1158/1055-9965.EPI-14-1363 · 4.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 02/2015; 33(8). DOI:10.1200/JCO.2014.57.8435 · 18.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted. Methods: 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having i) moderate (mean fluorescent intensity [MFI]≥484 & <1000) or ii) high seroreactivity (MFI≥1000). Associations of moderate and high HPV16 E6 seroreactivity with i) demographic risk factors; and seropositivity for ii) other HPV16 proteins (E1, E2, E4, E7 and L1) and iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45 and 52) were evaluated. Results: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking (odds ratio [OR] 5.5 [95% confidence interval [CI]:1.2-51.8]), and seropositivity against HPV16 L1 (OR 4.8, 95%CI:1.3-15.4); E2 (OR 7.7, 95%CI:1.4-29.1); multiple HPV16 proteins (OR 25.3, 95%CI:2.6-119.6 for 3 HPV16 proteins beside E6) and HPV33 E6 (OR 17.7, 95%CI:1.9-81.8). No associations were observed with moderate HPV16 E6 seroreactivity. Conclusions: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors. Impact: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 01/2015; 24(4). DOI:10.1158/1055-9965.EPI-14-1217 · 4.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.
    Leukemia 01/2015; 29(6). DOI:10.1038/leu.2015.2 · 10.43 Impact Factor
  • [Show abstract] [Hide abstract]
    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:
    JNCI Journal of the National Cancer Institute 01/2015; 107(1). DOI:10.1093/jnci/dju400 · 12.58 Impact Factor
  • [Show abstract] [Hide abstract]
    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; 135(2). DOI:10.1016/j.ygyno.2014.08.025 · 4.13 Impact Factor

Publication Stats

17k Citations
2,102.15 Total Impact Points


  • 2009-2015
    • Northern Inyo Hospital
      BIH, California, United States
  • 1993-2015
    • National Cancer Institute (USA)
      • • Division of Cancer Epidemiology and Genetics
      • • Infections and Immunoepidemiology
      • • Occupational and Environmental Epidemiology
      베서스다, Maryland, United States
    • University of New Mexico
      • Department of Cell Biology and Physiology
      Albuquerque, New Mexico, United States
  • 1990-2015
    • National Institutes of Health
      • • Division of Cancer Epidemiology and Genetics
      • • Branch of Biometric Research
      • • Branch of Occupational and Environmental Epidemiology
      베서스다, Maryland, United States
    • University of Milan
      Milano, Lombardy, Italy
  • 1995-2014
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 2012
    • DDL Diagnostic Laboratory
      Rijswijk, South Holland, Netherlands
  • 2007
    • Radboud University Nijmegen
      • Department of Medical Microbiology
      Nymegen, Gelderland, Netherlands
  • 1996-2006
    • Johns Hopkins University
      • Department of Pathology
      Baltimore, Maryland, United States
    • University of New Mexico Hospitals
      Albuquerque, New Mexico, United States
  • 2002
    • Columbia University
      New York, New York, United States
  • 2001
    • University of Pittsburgh
      • Department of Epidemiology
      Pittsburgh, Pennsylvania, United States
  • 2000
    • Kaiser Permanente
      • Department of Pathology
      Oakland, California, United States
  • 1999
    • Georgetown University
      Washington, Washington, D.C., United States