Allan Hildesheim

National Cancer Institute (USA), Maryland, United States

Are you Allan Hildesheim?

Claim your profile

Publications (281)1710.15 Total impact

  • [Show abstract] [Hide abstract]
    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;
  • [Show abstract] [Hide abstract]
    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;
  • The Journal of infectious diseases. 06/2014;
  • JAMA The Journal of the American Medical Association 06/2014; 311(23):2439. · 29.98 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
  • [Show abstract] [Hide abstract]
    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.
  • Source
    [Show abstract] [Hide abstract]
    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 &amp Prevention 04/2014; · 4.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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. · 3.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
  • Source
    [Show abstract] [Hide abstract]
    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. 01/2014; 4:119.
  • [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.
    Gynecologic Oncology. 01/2014;
  • Source
    [Show abstract] [Hide abstract]
    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. 01/2014;
  • Journal of Clinical Oncology 12/2013; · 18.04 Impact Factor
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Costa Rica HPV16/18 Vaccine Trial (CVT) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one, two, or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle (VLP) vaccine. Live-attenuated viral vaccines, but not simple-subunit vaccines, usually induce durable lifelong antibody responses after a single dose. It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard. To explore the likelihood that efficacy will persist longer term, we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment, vaccination, and annual visits through four years in four vaccinated groups; one-dose (n = 78), two-doses separated by one month (n = 140), two doses separated by six months (n = 52), and three scheduled doses (n = 120, randomly selected). We also tested enrollment sera from n = 113 HPV16- or HPV18 L1-seropositive women prevaccination, presumably from natural infection. At four years, 100% of women in all groups remained HPV16/18 seropositive; both HPV16/18 geometric mean titers (GMT) among the extended two-dose group were non-inferior to the three-dose group, and ELISA titers were highly correlated with neutralization titers in all groups. Compared with the natural infection group, HPV16/18 GMTs were, respectively, at least 24 and 14 times higher among the two-dose and 9 and 5 times higher among one-dose vaccinees. Antibody levels following one-dose remained stable from month 6 through month 48. Results raise the possibility that even a single dose of HPV VLPs will induce long-term protection. Cancer Prev Res; 6(11); 1242-50. ©2013 AACR.
    Cancer Prevention Research 11/2013; 6(11):1242-50. · 4.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Little is known about the epidemiology of oral human papillomavirus (HPV) in Latin America.Methods. Women (N = 5838) aged 22-29 in the control and vaccine arms of an HPV-16/18 vaccine trial in Costa Rica had oral, cervical, and anal specimens collected. Samples were tested for alpha mucosal HPV types (SPF10/LiPA25 version 1); a subset of oral samples (n = 500) was tested for cutaneous HPV types in the genera alpha, beta, gamma, mu, and nu.Results. In the control arm (n = 2926), 1.9% of women had an oral alpha mucosal HPV detected, 1.3% had carcinogenic HPV, and 0.4% had HPV-16; similar patterns for non-16/18 HPV types were observed in the vaccine arm. Independent risk factors for any oral alpha mucosal HPV among women in the control arm included marital status (adjusted odds ratio [AOR], 3.2; 95% confidence interval [CI], 1.8-5.7 for single compared to married/living as married), number of sexual partners (AOR, 2.4; 95% CI, 1.0-6.1 for ≥4 partners compared to 0-1 partners), chronic sinusitis (AOR, 3.1; 95% CI, 1.5-6.7), and cervical HPV infection (AOR, 2.6; 95% CI, 1.4-4.6). Detection of beta HPV was common (18.6%) and not associated with sexual activity.Conclusions. Unlike cutaneous HPV types, alpha mucosal HPV types were uncommon in the oral region and were predominately associated with sexual behavior.Clinical Trials Registration. NCT00128661.
    The Journal of Infectious Diseases 09/2013; · 5.85 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The impact of human papillomavirus (HPV) vaccination on cervical screening, colposcopy, and treatment is incompletely understood. In 2004-2005, investigators in the Costa Rica Vaccine Trial randomized 7,466 women aged 18-25 years, 1:1, to receive HPV vaccination or hepatitis A vaccination. The worst-ever cytology diagnosis and the 4-year cumulative proportions of colposcopy referral and treatment by vaccination arm were compared for 2 cohorts. The total vaccinated cohort included 6,844 women who provided cervical samples. The naive cohort included 2,284 women with no evidence of previous HPV exposure. In the total vaccinated cohort, HPV-vaccinated women had a significant (P = 0.01) reduction in cytological abnormalities: 12.4% for high-grade lesions and 5.9% for minor lesions. Colposcopy referral was reduced by 7.9% (P = 0.03) and treatment by 11.3% (P = 0.24). Greater relative reductions in abnormal cytology (P < 0.001) were observed for HPV-vaccinated women in the naive cohort: 49.2% for high-grade lesions and 18.1% for minor lesions. Colposcopy referral and treatment were reduced by 21.3% (P = 0.01) and 45.6% (P = 0.08), respectively, in the naive cohort. The overall impact on health services will be modest in the first years after vaccine introduction among young adult women, even in regions with high coverage.
    American journal of epidemiology 07/2013; · 5.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: High risk human papillomaviruses (HR-HPV) are known to be extremely common, sexually transmitted infections, but more information is needed regarding the absolute risks of type-specific HR-HPV infections in the years following sexual debut. We conducted a survival analysis of 3,737 women aged 18--25 from the control group of the Costa Rican Vaccine trial to determine the absolute risks of HR-HPV infections at 12 months, 24 months, and end of follow-up (average of 50.7 months). To corroborate determinants of infection, we used Cox proportional hazards methods to assess associations between demographics and sexual risk behaviors and incident HR-HPV. Cumulative incidence for HR-HPV infections was 51.3% at the end of the study period. The most common incident types were HPV52 (15.4%), HPV51 (13.6%), and HPV16 (12.4%). Type-specific cumulative incidence corresponded closely with type-specific prevalences, except that HPV16 was more prevalent than predicted by incidence, suggesting greater persistence. The strongest predictors of incident HR-HPV infections as a group in a multivariate analysis were the expected correlates of sexual behavior of the woman and her partner, such as being single (HR 1.6, 95% CI 1.4-1.8) or divorced/widowed (HR: 2.1, 95% CI: 1.7-2.7), having multiple HPV infections at enrollment (HR: 1.5, 95% CI: 1.3-1.7), and current smoking (HR: 1.2, 95% CI: 1.0-1.3). In women who reported being having only one lifetime sexual partner (being in a monogamous relationship), the strongest predictors of HR-HPV included not living with sex partner (HR: 2.1, 95% CI 1.7-2.5) and age of sex partner (HR: 1.4, 95% CI: 1.0-1.8). We confirm the extremely high incidence of HR-HPV in young women, emphasizing the importance of vaccinating young girls before sexual debut.
    BMC Infectious Diseases 07/2013; 13(1):308. · 3.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: While persistent carcinogenic human papillomvirus (HPV) infection is necessary for cervical carcinogenesis, the co-factors involved in HPV persistence and disease progression are poorly understood. Chronic cervical inflammation may increase risk, but few studies have measured immune markers (cytokines/chemokines/soluble receptors) in cervical secretions. We evaluated the performance of 74 multiplexed, bead-based immune markers in cervical secretions from three groups of women with biopsy evaluation of cervical intraepithelial neoplasia (CIN): 1) <CIN1, HPV-negative (n=24), 2) <CIN1, carcinogenic-HPV-positive (n=24), and 3) CIN2/3, carcinogenic-HPV-positive (n=48), matched on time since last period and smoking status. We considered markers with >25% detectability and >80% interclass correlation coefficients (ICC) acceptable for epidemiologic studies. Within-batch coefficients of variation (CV) of ≥25% indicated room for assay improvement. Secondarily, we explored associations between marker levels and CIN/HPV status adjusted for matching variables, assay batch, age, and number of sexual partners. Sixty-two markers (84%) had >25% detectability and ICCs>80%. Of those, 53 (85%) had CVs<25%. Using these preliminary data, we found that HPV-positivity was associated with increased eotaxin-1 (OR: 15.63, 95% CI: 1.26-200.00) and G-CSF (OR: 12.99, 95% CI: 1.10-142.86) among CIN-negative women. There was suggestive evidence that higher chemoattractant marker levels were associated with CIN2/3 (e.g., MIP-1delta, OR: 4.48, 95% CI: 0.87-23.04 versus <CIN1/HPV-positive). Over 70 percent of markers were reliably measured. This assay may be used to evaluate associations of immune-related markers with CIN and HPV status. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 07/2013; · 6.20 Impact Factor
  • PLoS ONE 07/2013; 8(7):68329-. · 3.73 Impact Factor

Publication Stats

12k Citations
1,710.15 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
  • 1990–2013
    • National Institutes of Health
      • • Division of Cancer Epidemiology and Genetics
      • • Laboratory of Cellular Oncology
      • • Branch of Occupational and Environmental Epidemiology
      Bethesda, MD, United States
  • 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
    • University of Pittsburgh
      • Department of Epidemiology
      Pittsburgh, PA, United States
    • Georgetown University
      • Lombardi Cancer Center
      Washington, Washington, D.C., United States
  • 1999
    • National Taiwan University
      • Graduate Institute of Epidemiology and Preventive Medicine
      Taipei, Taipei, Taiwan
    • Brown University
      Providence, Rhode Island, United States
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
    • Uniformed Services University of the Health Sciences
      • Department of Preventive Medicine & Biometrics
      Bethesda, MD, United States
    • Dartmouth College
      Hanover, New Hampshire, United States
  • 1998
    • Johns Hopkins Medicine
      • Department of Pathology
      Baltimore, MD, United States
    • George Washington University
      • Department of Pathology
      Washington, D. C., DC, United States
  • 1996
    • University of New Mexico Hospitals
      Albuquerque, New Mexico, United States
  • 1989
    • McMaster University
      Hamilton, Ontario, Canada