Howard D Strickler

Albert Einstein College of Medicine, New York, New York, United States

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Publications (196)976.66 Total impact

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    ABSTRACT: Background: HIV seropositive women face high risk for infection with oncogenic types of human papillomaviruses (oncHPV), abnormal Pap tests and precancer, but cervical cancer risk is only modestly increased. HPV16 is highly oncogenic but only weakly associated with HIV-status and immunosuppression, suggesting HPV16 may have a greater innate ability to evade host immune surveillance than other oncHPV types which in turn should result in a greater relative increase in the prevalence of other oncHPV types among women with cervical precancer. Objective: To assess whether the under-representation of HPV16 among HIV-seropositive relative to HIV-seronegative women remains among those with cervical precancers. Study design: HIV seropositive and seronegative women in the Women's Interagency HIV Study were screened for cervical intraepithelial neoplasia grade 3 or worse (CIN3+). DNA from >40 HPV types was detected by PCR in cervicovaginal lavage specimens obtained at the visit at which CIN3+ was diagnosed. Results: HPV16 was detected in 13 (62%) of 21 HIV-seronegative women with CIN3+ but only 44 (29%) of 154 HIV-seropositive CIN3+ (P=0.01). The lower prevalence of HPV16 in CIN3+ among HIV seropositive women persisted after controlling for covariates (O.R. 0.25, 95% C.I. 0.08, 0.78). The prevalence of other members of the HPV16-related alpha-9 oncHPV clade as a group was similar in HIV-infected and uninfected women with CIN3+ (OR=1.02, 95% C.I. 0.53, 1.94). The prevalence of non-alpha-9 oncHPV types was increased in HIV seropositive vs seronegative women with CIN3+ (OR=3.9, 95% C.I. 1.3, 11.8). Conclusions: The previously demonstrated increase in CIN3+ incidence among HIV seropositive women is associated with lower HPV16 and higher non-alpha-9 oncHPV prevalence. This is consistent with prior reports that HIV has a weak effect on infection by HPV16 relative to other oncHPV and supports use of nonavalent HPV vaccine in HIV seropositive women.
    American journal of obstetrics and gynecology 10/2015; DOI:10.1016/j.ajog.2015.09.086 · 4.70 Impact Factor
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    ABSTRACT: IFNL4-ΔG/TT (rs368234815) genotype is associated with hepatitis C virus clearance and may play a role in other infections. IFN-λ4 protein is generated only in individuals who carry the IFNL4-ΔG allele. The IFNL4 rs12979860-T allele, which is in strong linkage disequilib-rium with IFNL4-ΔG, was recently reported to be associated with more frequent and severe oral herpes episodes. We investigated the association of IFNL4-ΔG/TT with herpes simplex virus (HSV)-related outcomes among 2,192 African American and European American participants in the Women's Interagency HIV Study (WIHS). WIHS is a prospective cohort study of human immunodeficiency virus (HIV)–infected and at-risk women that began in 1994. This report includes follow-up through 2013. Available data included: HSV–1 and HSV–2 antibodies at study entry; biannually ascertained episodes of (self-reported) oral herpes, (self-reported) genital sores and (clinician-observed) genital ulcers; HSV–2 DNA in cervicovaginal lavage (CVL) specimens. IFNL4-ΔG/TT genotyping was determined by Taq-Man. We compared women with IFNL4-ΔG/ΔG or IFNL4-TT/ΔG genotypes (i.e., IFNL4-ΔG carriers) to those with the IFNL4-TT/TT genotype, adjusting for age, race and HIV status.
    PLoS ONE 10/2015; 10(10). DOI:10.1371/journal.pone.0138827 · 3.23 Impact Factor
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    ABSTRACT: Postmenopausal hormone therapy use has been associated with lower colorectal cancer risk in observational studies. However, the role of endogenous sex hormones in colorectal cancer development in postmenopausal women is uncertain. The relation of colorectal cancer risk with circulating levels of estradiol, estrone, free (bioactive) estradiol, progesterone and sex hormone-binding globulin (SHBG) was determined in a nested case-control study of 1203 postmenopausal women (401 case patients and 802 age and race/ethnicity-matched control patients) enrolled in the Women's Health Initiative Clinical Trial (WHI-CT) who were not assigned to the estrogen-alone or combined estrogen plus progestin intervention groups. We used multivariable-adjusted conditional logistic regression models that included established colorectal cancer risk factors. All statistical tests were two-sided. Comparing extreme quartiles, estrone (odds ratio [OR]q4-q1 = 0.44, 95% confidence interval [CI] = 0.28 to 0.68, P trend = .001), free estradiol (ORq4-q1 = 0.43, 95% CI = 0.27 to 0.69, P trend ≤ .0001), and total estradiol (ORq4-q1 = 0.58, 95% CI = 0.38 to 0.90, P trend = .08) were inversely associated with colorectal cancer risk. SHBG levels were positively associated with colorectal cancer development (OR[q4-q1] = 2.30, 95% CI = 1.51 to 3.51, P trend ≤ .0001); this association strengthened after further adjustment for estradiol and estrone (ORq4-q1 = 2.50, 95% CI = 1.59 to 3.92, P trend < .0001). Progesterone was not associated with colorectal cancer risk. Endogenous estrogen levels were inversely, and SHBG levels positively, associated with colorectal cancer risk, even after control for several colorectal cancer risk factors. These results suggest that endogenous estrogens may confer protection against colorectal tumorigenesis among postmenopausal women. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    Journal of the National Cancer Institute 10/2015; 107(10). DOI:10.1093/jnci/djv210 · 12.58 Impact Factor
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    ABSTRACT: Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer, yet epidemiologic data on their associations with breast cancer risk are limited. In a case-cohort analysis nested within the Women's Health Initiative Observational Study, a prospective cohort of postmenopausal women, baseline plasma samples from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines, namely leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α, hepatocyte growth factor, and plasminogen activator inhibitor-1, and for C-reactive protein (CRP), an inflammatory marker. Data were analyzed by multivariable Cox modeling that included established breast cancer risk factors and previously measured estradiol and insulin levels. All statistical tests were two-sided. The association between plasma CRP levels and breast cancer risk was dependent on hormone therapy (HT) use at baseline (P interaction = .003). In a model that controlled for multiple breast cancer risk factors including body mass index (BMI), estradiol, and insulin, CRP level was positively associated with breast cancer risk among HT nonusers (hazard ratio for high vs low CRP levels = 1.67, 95% confidence interval = 1.04 to 2.68, P trend = .029). None of the other adipokines were statistically significantly associated with breast cancer risk. Following inclusion of CRP, insulin, and estradiol in a multivariable model, the association of BMI with breast cancer was attenuated by 115%. These data indicate that CRP is a risk factor for postmenopausal breast cancer among HT nonusers. Inflammatory mediators, together with insulin and estrogen, may play a role in the obesity-breast cancer relation. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    Journal of the National Cancer Institute 09/2015; 107(9). DOI:10.1093/jnci/djv169 · 12.58 Impact Factor
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    ABSTRACT: Plasma HIV RNA is the most significant determinant of cervical HIV shedding. However, shedding is also associated with sexually transmitted infections (STIs) and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, replication and HIV disease progression. We hypothesized that systemic immune activation would be associated with an increase in HIV genital shedding. Clinical assessments, HIV RNA in plasma and genital secretions, and markers of immune activation (CD38+DR+ and CD38-DR-) on CD4+ and CD8+ T cells in blood were evaluated in 226 HIV+ women enrolled in the Women's Interagency HIV Study. There were 569 genital evaluations of which 159 (28%) exhibited HIV RNA shedding, defined as HIV viral load > 80 copies/ml. We tested associations between immune activation and shedding using generalized estimating equations with logit link function. In the univariate model, higher levels of CD4+ and CD8+ T cell activation in blood were significantly associated with genital tract shedding. However, in the multivariate model adjusting for plasma HIV RNA, STIs and genital tract infections, only higher levels of resting CD8+ T cells (CD38-DR- ) were significantly inversely associated with HIV shedding in the genital tract (OR=0.44, 95% CI= 0.21-0.9, P= 0.02). The association of systemic immune activation with genital HIV shedding is multifactorial. Systemic T cell activation is associated with genital tract shedding in univariate analysis but not when adjusting for plasma HIV RNA, STIs and genital tract infections. In addition, women with high percentage of resting T cells are less likely to have HIV shedding compared to those with lower percentages. These findings suggest that a higher percentage of resting cells, as a result of maximal viral suppression with treatment, may decrease local genital activation, HIV shedding, and transmission.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2015; DOI:10.1097/QAI.0000000000000823 · 4.56 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):937-937. DOI:10.1158/1538-7445.AM2015-937 · 9.33 Impact Factor

  • JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2015; DOI:10.1097/QAI.0000000000000832 · 4.56 Impact Factor
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    ABSTRACT: Background: Determining cervical precancer risk among human immunodeficiency virus (HIV)-infected women who despite a normal Pap test are positive for oncogenic human papillomavirus (oncHPV) types is important for setting screening practices. Methods: A total of 2791 HIV-infected and 975 HIV-uninfected women in the Women's Interagency HIV Study were followed semiannually with Pap tests and colposcopy. Cumulative risks of cervical intraepithelial neoplasia grade 2 or greater (CIN-2+; threshold used for CIN treatment) and grade 3 or greater (CIN-3+; threshold to set screening practices) were measured in HIV-infected and HIV-uninfected women with normal Pap tests, stratified by baseline HPV results, and also in HIV-infected women with a low-grade squamous intraepithelial lesion (LSIL; benchmark indication for colposcopy). Results: At baseline, 1021 HIV-infected and 518 HIV-uninfected women had normal Pap tests, of whom 154 (15%) and 27 (5%), respectively, tested oncHPV positive. The 5-year CIN-2+ cumulative risk in the HIV-infected oncHPV-positive women was 22% (95% confidence interval [CI], 9%-34%), 12% (95% CI, 0%-22%), and 14% (95% CI, 2%-25%) among those with CD4 counts <350, 350-499, and ≥500 cells/µL, respectively, whereas it was 10% (95% CI, 0%-21%) in those without HIV. For CIN-3+, the cumulative risk averaged 4% (95% CI, 1%-8%) in HIV-infected oncHPV-positive women, and 10% (95% CI, 0%-23%) among those positive for HPV type 16. In HIV-infected women with LSIL, CIN-3+ risk was 7% (95% CI, 3%-11%). In multivariate analysis, HIV-infected HPV16-positive women had 13-fold (P = .001) greater CIN-3+ risk than oncHPV-negative women (referent), and HIV-infected women with LSIL had 9-fold (P < .0001) greater risk. Conclusions: HIV-infected women with a normal Pap result who test HPV16 positive have high precancer risk (similar to those with LSIL), possibly warranting immediate colposcopy. Repeat screening in 1 year may be appropriate if non-16 oncHPV is detected.
    Clinical Infectious Diseases 07/2015; DOI:10.1093/cid/civ569 · 8.89 Impact Factor
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    ABSTRACT: Genetic polymorphisms within the interferon lambda (IFN-) region are strongly associated with hepatitis C virus (HCV) clearance; the IFNL4-ΔG/TT (rs368234815) polymorphism, which controls generation of the IFN-4 protein, is more strongly associated with HCV clearance than rs12979860 (the 'IL28B variant'). An IFNL3 3' untranslated region polymorphism (rs4803217) has been proposed as a causal variant that may affect HCV clearance by altering IFNL3 mRNA stability. We compared IFNL4-ΔG/TT and rs4803217 for association with response to pegylated-IFN-α/ribavirin in the VIRAHEP-C and HALT-C trials, and spontaneous HCV clearance in the ALIVE, UHS and WIHS studies. Genotyping was performed with TaqMan assays. We compared differences in mean reduction in HCV RNA levels by genotype and haplotype. For HCV clearance, we calculated p-values comparing c-statistics for IFNL4-ΔG/TT and rs4803217 genotypes by a bootstrap approach. Among European Americans, linkage disequilibrium between IFNL4-ΔG/TT and rs4803217 was strong (r(2)=0.89-0.99) and there were no significant differences between the variants. In African American (AA) individuals enrolled in VIRAHEP-C, HCV RNA at treatment day 28 was more strongly associated with IFNL4-ΔG/TT than rs4803217 (p=0.003); the IFNL4-ΔG:rs4803217-G haplotype, which includes the putatively favorable IFNL3 allele, was actually associated with the poorest day 28 response (p=0.03, comparison to IFNL4-ΔG:rs4803217-T haplotype). Among AA participants, associations were stronger for IFNL4-ΔG/TT than rs4803217 for undetectable HCV RNA at week 24 in Virahep C (p=0.03) and week 20 in HALT-C (p=0.03), as well as for spontaneous HCV clearance (p=0.048). IFNL4-ΔG/TT is the primary IFN- region polymorphism for impaired HCV clearance. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 07/2015; 63(5). DOI:10.1016/j.jhep.2015.06.035 · 11.34 Impact Factor

  • JAIDS Journal of Acquired Immune Deficiency Syndromes 07/2015; 70(2). DOI:10.1097/QAI.0000000000000752 · 4.56 Impact Factor
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    ABSTRACT: African Americans coinfected with HIV and hepatitis C virus (HCV) have lower liver-related mortality than Caucasians and Hispanics. While genetic polymorphisms near the IFNL3 and IFNL4 genes explain a significant fraction of racial differences in several HCV-related outcomes, the impact of these variants on liver-related mortality has not been investigated. We conducted a cohort study of HIV/HCV-coinfected women followed in the multicentre, NIH-funded Women's Interagency HIV Study (WIHS) to investigate whether 10 polymorphisms spanning the IFN-λ region were associated with liver-related mortality by dominant, recessive or additive genetic models. We also considered whether these polymorphisms contributed to previously reported differences in liver-related death by race/ethnicity (ascertained by self-report and ancestry informative markers). Among 794 coinfected women, there were 471 deaths including 55 liver-related deaths during up to 18 years of follow-up. On adjusted analysis, rs12980275 GG genotype compared to AG+AA hazards ratios [(HR) 0.36, 95% CI 0.14-0.90, P = 0.029] and rs8109886 AA genotype compared to CC+AC (HR 0.67, 95% CI 0.45-0.99, P = 0.047) were most strongly associated with liver-related death although these associations were no longer significant after adjusting for race/ethnicity (HR 0.41, 95% CI 0.16-1.04, P = 0.060 and HR 0.78, 95% CI 0.51-1.19, P = 0.25, respectively). African American women had persistently lower liver-related death independent of IFN-λ variants (HRs ≤ 0.44, P values ≤ 0.04). The lower risk of death among African American HIV/HCV-coinfected women is not explained by genetic variation in the IFN-λ region suggesting, that other genetic, behavioural and/or environmental factors may contribute to racial/ethnic differences in liver-related mortality. © 2015 John Wiley & Sons Ltd.
    Journal of Viral Hepatitis 06/2015; 22(12). DOI:10.1111/jvh.12431 · 3.91 Impact Factor
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    ABSTRACT: Atypical hyperplasia of the breast (AH) is associated with increased risk of subsequent invasive breast cancer, yet little is known about the etiology of AH. Insulin-like growth factor binding protein 2 (IGFBP-2) may contribute to the development of AH due to its proliferative effects on mammary tissue. We conducted a nested case-control study of postmenopausal women enrolled in Women’s Health Initiative-Clinical Trial. Cases were 275 women who developed incident AH during follow-up, individually (1 : 1) matched to controls. Levels of IGFBP-2 were determined from fasting serum collected at baseline. Multivariable conditional logistic regression models were used to estimate odds ratios for the association of IGFBP-2 with risk of AH. Serum IGFBP-2 was associated with a nonsignificant decrease in risk for AH, when comparing the highest quartile to lowest quartile (OR = 0.65; 95% CI = 0.32–1.31). This decrease in risk was most evident when analyses were restricted to nondiabetic, nonusers of hormone therapy (OR = 0.33, 95% CI = 0.13–0.86, p trend = 0.06) and nondiabetic women who were overweight or obese (OR = 0.43, 95% CI = 0.18–1.03, p trend = 0.05). Results from this study provide some support for an inverse association between serum IGFBP2 levels and risk of AH, particularly in nondiabetic women who are overweight or obese. Further studies are required to confirm these results.
    Journal of Cancer Epidemiology 06/2015; 2015(24):1-7. DOI:10.1155/2015/203284
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    ABSTRACT: Study objective: The increasing prevalence of adolescent obesity has led to consideration of the potential effect of obesity on risky sexual behaviors. In the current study we examined whether body mass index (BMI) was related to age at sexual debut, type of sexual behavior, partner number, and condom use in a population of adolescent women at high risk for obesity and risky sexual behaviors. Design, setting, and participants: Cross-sectional examination of 860 sexually active, predominantly minority, adolescent women who received medical care at an urban health center from 2007 through 2013. Intervention and main outcome measures: Self-reported age at sexual debut, types of sexual intercourse, number of partners and condom use was compared with clinically assessed BMI. Results: BMI was positively associated with number of sexual partners (P = .001) and history of attempted anal intercourse (P = .002). An inverse association was observed with age at first anal intercourse (P = .040). Conclusion: In this sample of adolescent women, increased BMI was associated with riskier sexual practices at a younger age. Results of this study suggest that overweight and obese adolescents are a vulnerable population who might need targeted sexual health counseling.
    Journal of Pediatric and Adolescent Gynecology 06/2015; DOI:10.1016/j.jpag.2015.06.003 · 1.68 Impact Factor
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    ABSTRACT: This study investigated the association of cervical human papillomavirus (HPV) infection with cumulative psychosocial risk reflecting family disadvantage, psychological distress, and unhealthy lifestyle. The sample (N = 745) comprised sexually active female adolescent patients (12-19 yr), primarily ethnic minorities, enrolled in a free HPV vaccination program. Subjects completed questionnaires and provided cervical swabs for HPV DNA testing. Unweighted and weighted principal component analyses for categorical data were used to derive multisystemic psychosocial risk indices using 9 indicators: low socioeconomic status, lack of adult involvement, not attending high school/college, history of treatment for depression/anxiety, antisocial/delinquent behavior, number of recent sexual partners, use of alcohol, use of drugs, and dependency risk for alcohol/drugs. The association between cervical HPV (any type, high-risk types, vaccine types) assayed by polymerase chain reaction and self-reported number of psychosocial risk indicators was estimated using multivariable logistic regression. Subjects had a median of 3 psychosocial risk indicators. Multiple logistic regression analyses showed associations with unweighted and weighted number of psychosocial indicators for HPV any type (adjusted odds ratio [aOR] = 1.1; 95% confidence interval [CI], 1.0-1.2), with the strongest associations between weighted drug/alcohol use, drug/alcohol dependency risk, and antisocial/delinquent behavior and detection of HPV vaccine types (aOR = 1.5; 95% CI, 1.1-2.0) independent of number of recent sexual partners and vaccine dose (0-3). Increased HPV infections including HPV vaccine types were associated with greater number of psychosocial risk indicators even after controlling for demographics, sexual behavior, history of chlamydia, and vaccine dose.
    Journal of developmental and behavioral pediatrics: JDBP 05/2015; 36(8). DOI:10.1097/DBP.0000000000000178 · 2.13 Impact Factor
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    ABSTRACT: The association between oral HPV16 DNA viral load and infection clearance was evaluated among 88 individuals with oral HPV16 infection identified within a prospective cohort of 1,470 HIV-infected and uninfected individuals. Oral rinses were collected semi-annually for up to five years. Oral HPV16 viral load at the first positive test was significantly associated with time to clearance of infection (continuous p-trends<0.01). Notably, clearance rates by 24-month were 41% and 94% in the highest and lowest HPV16 viral load tertiles (p=0.03), respectively. High oral HPV16 viral load warrants consideration as a biomarker for infection persistence, the presumed precursor of HPV16-associated oropharyngeal cancer. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:
    The Journal of Infectious Diseases 05/2015; DOI:10.1093/infdis/jiv273 · 6.00 Impact Factor
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    ABSTRACT: Objectives To determine whether changes in insulin-like growth factor (IGF) protein levels are greater in participants with type 2 diabetes mellitus or worsening glycemia than in normoglycemic individuals over a 9-year follow-up period.DesignRetrospective analysis of a cohort study.SettingParticipants were recruited from North Carolina, California, Maryland, and Pennsylvania.ParticipantsCardiovascular Health Study All Stars participants, a cohort study of community-dwelling adults aged 65 and older (N = 897).MeasurementsPlasma IGF-I, IGF binding protein (IGFBP)-1, and IGFBP-3 levels were assessed and American Diabetes Association cut-points for impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and diabetes mellitus were used to classify participants at baseline (1996–97) and follow-up (2005–06).ResultsAt baseline, mean age was 76.3 ± 3.6, and 18.5% had diabetes mellitus. Participants with IFG alone and IGT plus IFG had higher IGF-I levels and lower IGFBP-1 levels than those with normoglycemia or diabetes mellitus. The greatest percentage change in IGF levels occurred in those who had diabetes mellitus at baseline (9-year changes: −9.3% for IGF-I, 59.7% for IGFBP-1, −13.4% for IGFBP-3), the smallest in individuals who remained normoglycemic at follow-up (9-year changes: −3.7% for IGF-I, 25.6% for IGFBP-1, −6.4% for IGFBP-3), and intermediate in those who were normoglycemic but developed IFG at follow-up.Conclusion Degrees of glycemic impairment are associated with varying degrees of change in IGF protein levels. The changes observed in the diabetes mellitus group have been previously shown to be associated with heart failure, cancer, and noncancer mortality.
    Journal of the American Geriatrics Society 05/2015; 63(5). DOI:10.1111/jgs.13390 · 4.57 Impact Factor
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    ABSTRACT: To describe changes in knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination among women at high risk for cervical cancer in the first five years after introduction of HPV vaccination. In 2007, 2008-9, and 2011, women in a multicenter U.S. cohort study completed 44-item self-report questionnaires assessing knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results across time were assessed for individuals, and three study enrollment cohorts were compared. Knowledge scores were correlated with demographic variables, measures of education and attention, and medical factors. Associations were assessed in multivariable models. In all, 974 women completed three serial questionnaires; most were minority, low income, and current or former smokers. The group included 652 (67%) HIV infected and 322 (33%) uninfected. Summary knowledge scores (possible range 0-24) increased from 2007 (12.8, S.D. 5.8) to 2008-9 (13.9, S.D. 5.3, P < 0.001) and to 2011 (14.3, S.D 5.2, P < 0.0001 vs 2007 and <0.04 vs 2008-9). Higher knowledge scores at first and follow-up administration of questionnaires, higher income, and higher education level were associated with improved knowledge score at third administration. Women not previously surveyed had scores similar to those of the longitudinal group at baseline. Substantial gaps in understanding of HPV and cervical cancer prevention exist despite years of health education. While more effective educational interventions may help, optimal cancer prevention may require opt-out vaccination programs that do not require nuanced understanding.
    04/2015; 12. DOI:10.1016/j.gore.2015.02.007
  • Xiaonan Xue · Mimi Y Kim · Tao Wang · Mark H Kuniholm · Howard D Strickler ·
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    ABSTRACT: Longitudinal studies of rare events such as cervical high-grade lesions or colorectal polyps that can recur often involve correlated binary data. Risk factor for these events cannot be reliably examined using conventional statistical methods. For example, logistic regression models that incorporate generalized estimating equations often fail to converge or provide inaccurate results when analyzing data of this type. Although exact methods have been reported, they are complex and computationally difficult. The current paper proposes a mathematically straightforward and easy-to-use two-step approach involving (i) an additive model to measure associations between a rare or uncommon correlated binary event and potential risk factors and (ii) a permutation test to estimate the statistical significance of these associations. Simulation studies showed that the proposed method reliably tests and accurately estimates the associations of exposure with correlated binary rare events. This method was then applied to a longitudinal study of human leukocyte antigen (HLA) genotype and risk of cervical high grade squamous intraepithelial lesions (HSIL) among HIV-infected and HIV-uninfected women. Results showed statistically significant associations of two HLA alleles among HIV-negative but not HIV-positive women, suggesting that immune status may modify the HLA and cervical HSIL association. Overall, the proposed method avoids model nonconvergence problems and provides a computationally simple, accurate, and powerful approach for the analysis of risk factor associations with rare/uncommon correlated binary events. © The Author(s) 2015 Reprints and permissions:
    Statistical Methods in Medical Research 04/2015; DOI:10.1177/0962280215581112 · 4.47 Impact Factor
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    ABSTRACT: To evaluate the association of 3 hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) use and concordant polypharmacy with disease-specific survival from endometrial cancer. A retrospective cohort study was conducted of 985 endometrial cancer cases treated from January 1999 through December 2009 at a single institution. Disease-specific survival was estimated by Kaplan-Meier analyses. A Cox proportional hazards model was used to study factors associated with survival. All statistical tests were two-sided and performed using Stata. At the time of analysis, 230 patients (22% of evaluable patients) died of disease and median follow-up was 3.28 years. Disease-specific survival was greater (179/220 [81%]) for women with endometrial cancer taking statin therapy at the time of diagnosis and staging compared with women not using statins (423/570 [74%]) (log rank test, P=.03). This association persisted for the subgroup of patients with nonendometrioid endometrial tumors who were statin users (59/87 [68%]) compared with nonusers (93/193 [43%]) (log rank test, P=.02). The relationship remained significant (hazard ratio 0.63, 95% confidence interval [CI] 0.40-0.99) after adjusting for age, clinical stage, radiation, and other factors. Further evaluation of polypharmacy showed an association between concurrent statin and aspirin use with an especially low disease-specific mortality (hazard ratio 0.25, 95% CI 0.09-0.70) relative to those who used neither. Statin and aspirin use was associated with improved survival from nonendometrioid endometrial cancer.
    Gynecologic Oncology 04/2015; 137(1). DOI:10.1016/j.ygyno.2015.01.074 · 3.77 Impact Factor
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    ABSTRACT: Although overall there is a positive association between obesity and risk of prostate cancer (PrCa) recurrence, results of individual studies are somewhat inconsistent. We investigated whether the failure to exclude diabetics in prior studies could have increased the likelihood of conflicting results. A total of 610 PrCa patients who underwent radical prostatectomy between 2005 and 2012 were followed for recurrence, defined as a rise in serum PSA ≥ 0.2 ng/ml following surgery. Body mass index (BMI) and history of type 2 diabetes were documented prior to PrCa surgery. The analysis was conducted using Cox proportional hazard models. Obesity (25.6 %) and diabetes (18.7 %) were common in this cohort. There were 87 (14.3 %) recurrence events during a median follow-up of 30.8 months after surgery among the 610 patients. When analyzed among all PrCa patients, no association was observed between BMI/obesity and PrCa recurrence. However, when analysis was limited to non-diabetics, obese men had a 2.27-fold increased risk (95 % CI 1.17-4.41) of PrCa recurrence relative to normal weight men, after adjusting for age and clinical/pathological tumor characteristics. This study found a greater than twofold association between obesity/BMI and PrCa recurrence in non-diabetics. We anticipated these results because the relationship between BMI/obesity and the biologic factors that may underlie the PrCa recurrence-BMI/obesity association, such as insulin, may be altered by the use of anti-diabetes medication or diminished beta-cell insulin production in advanced diabetes. Studies to further assess the molecular factors that explain the BMI/obesity-PrCa recurrence relationship are warranted.
    Cancer Causes and Control 03/2015; 26(6). DOI:10.1007/s10552-015-0554-z · 2.74 Impact Factor

Publication Stats

5k Citations
976.66 Total Impact Points


  • 1999-2015
    • Albert Einstein College of Medicine
      • Department of Epidemiology & Population Health
      New York, New York, United States
  • 2014
    • Regional Alliance for Sustainable Development (RASD Rwanda)
      Kigale, Kigali, Rwanda
  • 2013
    • Cook County Health and Hospitals System
      Chicago, Illinois, United States
  • 2011
    • Montefiore Medical Center
      New York, New York, United States
  • 2005-2011
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, California, United States
  • 2009
    • University of Illinois Springfield
      Спрингфилд, Florida, United States
  • 2008-2009
    • Yeshiva University
      • Department of Epidemiology & Population Health
      New York, New York, United States
  • 2007
    • Southern Illinois University School of Medicine
      • Department of Obstetrics and Gynecology
      Springfield, IL, United States
    • University of Pittsburgh
      • Department of Medicine
      Pittsburgh, Pennsylvania, United States
    • University of Texas Southwestern Medical Center
      • Division of Epidemiology
      Dallas, TX, United States
  • 2004-2007
    • University of Southern California
      • • Department of Pediatrics
      • • Keck School of Medicine
      Los Angeles, CA, United States
    • Lincoln Hospital
      New York, United States
    • Cook County Hospital
      Chicago, Illinois, United States
  • 1995-2001
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      베서스다, Maryland, United States
  • 1998
    • Johns Hopkins Bloomberg School of Public Health
      • Department of Epidemiology
      Baltimore, Maryland, United States
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 1997-1998
    • National Institutes of Health
      베서스다, Maryland, United States
  • 1995-1997
    • Northern Inyo Hospital
      BIH, California, United States