Nicolas F Schlecht

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

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Publications (76)275.51 Total impact

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    ABSTRACT: Oral cancer is a major public health issue in India with approximately 77,000 new cases and 52,000 deaths yearly. Paan chewing, tobacco and alcohol use are strong risk factors for this cancer in India. Human papillomaviruses (HPV) are also related to a subset of head and neck cancers. We examined the association between oral HPV and oral cancer in a sample of Indian subjects participating in a hospital-based case-control study. We recruited incident oral cancer cases (N=350) and controls frequency-matched by age and sex (N=371) from two main referral hospitals in Kerala, South India. Socio-demographic and behavioral data were collected by interviews. Epithelial cells were sampled using Oral CDx® brushes from the oral cancer site and the normal mucosa. Detection and genotyping of 36 HPV genotypes were done using a polymerase chain reaction protocol. Data collection procedures were performed by qualified dentists via a detailed protocol with strict quality control, including independent HPV testing in India and Canada. HPV DNA was detected in none of the cases or controls. Associations between oral cancer and risk factors usually associated with HPV infection, such as oral sex and number of lifetime sexual partners, were examined by logistic regression and were not associated with oral cancer. Lack of a role for HPV infection in this study may reflect cultural or religious characteristics specific to this region in India that are not conducive to oral HPV transmission. A nationwide representative prevalence study is needed to investigate HPV prevalence variability among Indian regions. This article is protected by copyright. All rights reserved. © 2014 Wiley Periodicals, Inc. © 2015 UICC.
    International Journal of Cancer 08/2015; DOI:10.1002/ijc.29827 · 5.01 Impact Factor
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    ABSTRACT: Context .- Oropharyngeal squamous cell carcinoma is associated both with tobacco use and with human papillomavirus (HPV) infection. It is argued that carcinogen-driven tumorigenesis is a distinct disease from its virally driven counterpart. We hypothesized that tumorigenesis is the result of a loss of genotypic robustness resulting in an increase in phenotypic variation in tumors compared with adjacent histologically normal tissues, and that carcinogen-driven tumorigenesis results in greater variation than its virally driven counterpart. Objectives .- To examine the loss of robustness in carcinogen-driven and virally driven oropharyngeal squamous cell carcinoma samples, and to identify potential pathways involved. Design .- We used coefficients of variation for messenger RNA and microRNA expression to measure the loss of robustness in oropharyngeal squamous cell carcinoma samples. Tumors were compared with matched normal tissues, and were further categorized by HPV and patient smoking status. Weighted gene coexpression networks were constructed for genes with highly variable expression among the HPV(-) tumors from smokers. Results .- We observed more genes with variable messenger RNA expression in tumors compared with normal tissues, regardless of HPV and smoking status, and more microRNAs with variable expression in HPV(-) and HPV(+) tumors from smoking patients than from nonsmokers. For both the messenger RNA and microRNA data, we observed more variance among HPV(-) tumors from smokers compared with HPV(+) tumors from nonsmokers. The gene coexpression network construction highlighted pathways that have lost robustness in carcinogen-induced tumors but appear stable in virally induced tumors. Conclusion .- Using coefficients of variation and coexpression networks, we identified multiple altered pathways that may play a role in carcinogen-driven tumorigenesis.
    Archives of pathology & laboratory medicine 07/2015; DOI:10.5858/arpa.2014-0624-OA · 2.88 Impact Factor
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    ABSTRACT: The increasing prevalence of adolescent obesity has led to consideration of the potential effect of obesity on risky sexual behaviors. The current study 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.
    Journal of Pediatric and Adolescent Gynecology 06/2015; DOI:10.1016/j.jpag.2015.06.003 · 1.81 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; DOI:10.1097/DBP.0000000000000178 · 2.12 Impact Factor
  • Nicole V J Anayannis · Nicolas F Schlecht · Thomas J Belbin
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    ABSTRACT: Context .- Growing evidence suggests that as many as half of all oropharyngeal squamous cell carcinomas (OPSCCs) harbor human papillomavirus (HPV) infections. Despite being more advanced at diagnosis, HPV-positive OPSCCs are associated with a better response to therapy and longer patient survival than HPV-negative OPSCCs. Human papillomavirus-positive OPSCC has also been shown to have distinct host gene expression profiles compared with HPV-negative OPSCC. Recently, this distinction has been shown to include the epigenome. It is well supported that cancers are epigenetically deregulated. This review highlights epigenetic differences between HPV-positive and HPV-negative OPSCCs. The epigenetic mechanisms highlighted include methylation changes to host and viral DNA, and host chromatin modification. We also review the current evidence regarding host DNA methylation changes associated with smoking, and deregulation of microRNA expression in HPV-positive OPSCC. Objective .- To provide an overview of epigenetic mechanisms reported in HPV-positive OPSCC, with analogies to cervical cancer, and discussion of the challenges involved in studying epigenetic changes in HPV-associated OPSCC in combination with changes associated with smoking. Data Sources .- Sources were a literature review of peer-reviewed articles in PubMed on HPV and either OPSCC or head and neck squamous cell carcinoma, and related epigenetic mechanisms. Conclusions .- Epigenetic changes are reported to be a contributing factor to maintaining a malignant phenotype in HPV-positive OPSCC. The epigenetic mechanisms highlighted in this review can be studied for potential as biomarkers or as drug targets. Furthermore, continued research on the deregulation of epigenetic mechanisms in HPV-positive OPSCC (compared with HPV-negative OPSCC) may contribute to our understanding of the clinical and biologic differences between HPV-positive and HPV-negative OPSCC.
    Archives of pathology & laboratory medicine 05/2015; DOI:10.5858/arpa.2014-0554-RA · 2.88 Impact Factor
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    ABSTRACT: We evaluated the risk factors associated with oral human papillomavirus (HPV) infection and oral lesions in 161 HIV-positive and 128 HIV-negative patients presenting for oral examination at two urban health-care centers. Patients were interviewed on risk factors and provided oral-rinse samples for HPV-DNA typing by PCR. Statistical associations were assessed by logistic regression. Oral HPV was prevalent in 32% and 16% of HIV-positive and negative patients, including high-risk type 16 (8% and 2%, respectively, p=0.049) and uncommon types 32/42 (6% and 5%, p=0.715). Among HIV-negative patients, significant risk factors for oral HPV included multiple sexual partners (≥21 vs. ≤5; odds ratio [OR]=9.1, 95% confidence interval [CI]:1.7-49.3), heavy tobacco smoking (>20 pack-years vs. none; OR=9.2, 95%CI:1.4-59.4), and marijuana use (OR=4.0, 95%CI:1.3-12.4). Among HIV-positive patients, lower CD4 count only was associated with oral HPV detection (≤200 vs. ≥500 T-cells/mm(3); OR=4.5, 95%CI:1.3-15.5). Detection of high-risk HPV was also associated with concurrent detection of potentially cancerous oral lesions in HIV-negative patients but not among HIV-positive patients. The observed risk factor associations with oral HPV in HIV-negative patients are consistent with sexual transmission and local immunity, whereas in HIV-positive patients, oral HPV detection is strongly associated with low CD4 count. © 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 02/2015; DOI:10.1093/infdis/jiv080 · 5.78 Impact Factor
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    ABSTRACT: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is recognized as a distinct disease entity associated with improved survival. DNA hypermethylation profiles differ significantly by HPV status suggesting that a specific subset of methylated CpG loci could give mechanistic insight into HPV-driven OPSCC. We analyzed genome-wide DNA methylation of primary tumor samples and adjacent normal mucosa from 46 OPSCC patients undergoing treatment at Montefiore Medical Center, Bronx, NY using the Illumina HumanMethylation27 beadchip. For each matched tissue set, we measured differentially methylated CpG loci using a change in methylation level (M value). From these analyses, we identified a 22 CpG loci panel for HPV+ OPSCC that included four CDKN2A loci downstream of the p16(INK4A) and p14(ARF) transcription start sites. This panel was significantly associated with overall HPV detection (P < 0.05; ROC area under the curve = 0.96, 95% CI: 0.91–1.0) similar to the subset of four CDKN2A-specific CpG loci (0.90, 95% CI: 0.82–0.99) with equivalence to the full 22 CpG panel. DNA hypermethylation correlated with a significant increase in alternative open reading frame (ARF) expression in HPV+ OPSCC primary tumors, but not to the other transcript variant encoded by the CDKN2A locus. Overall, this study provides evidence of epigenetic changes to the downstream region of the CDKN2A locus in HPV+ oropharyngeal cancer that are associated with changes in expression of the coded protein products.
    Cancer Medicine 12/2014; 4(3). DOI:10.1002/cam4.374
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    ABSTRACT: While its prognostic significance remains unclear, p16INK4a protein expression is increasingly being used as a surrogate marker for oncogenic human papillomavirus (HPV) infection in head and neck squamous cell carcinomas (HNSCC). To evaluate the prognostic utility of p16 expression in HNSCC, we prospectively collected 163 primary tumor specimens from histologically confirmed HNSCC patients who were followed for up to 9.4 years. Formalin fixed tumor specimens were tested for p16 protein expression by immunohistochemistry. HPV type-16 DNA and RNA was detected by MY09/11-PCR and E6/E7 RT-PCR on matched frozen tissue, respectively. P16 protein expression was detected more often in oropharyngeal tumors (53%) as compared with laryngeal (24%), hypopharyngeal (8%), or oral cavity tumors (4%; P<0.0001). With respect to prognosis, p16-positive oropharyngeal tumors exhibited significantly better overall survival than p16-negative tumors (log-rank test p=0.04), whereas no survival benefit was observed for non-oropharyngeal tumors. However, when both p16 and HPV DNA test results were considered, concordantly positive non-oropharyngeal tumors had significantly better disease-specific survival than concordantly negative non-oropharyngeal tumors after controlling for sex, nodal stage, tumor size, tumor subsite, primary tumor site number, smoking, and drinking (adjusted hazard ratio [HR]=0.04, 0.01–0.54). Compared with concordantly negative non-oropharyngeal HNSCC, p16(+)/HPV16(-) non-oropharyngeal HNSCC (n=13, 7%) demonstrated no significant improvement in disease-specific survival when HPV16 was detected by RNA (adjusted HR=0.83, 0.22–3.17). Our findings show that p16 immunohistochemistry alone has potential as a prognostic test for oropharyngeal cancer survival, but combined p16/HPV testing is necessary to identify HPV-associated non-oropharyngeal HNSCC with better prognosis. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 11/2014; 135(10). DOI:10.1002/ijc.28876 · 5.01 Impact Factor
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    ABSTRACT: Human papillomavirus (HPV) positive head and neck squamous cell carcinoma (HNSCC) accounts for 25% of HNSCCs and frequently presents with neck lymph node metastases. We investigated utilizing cytology needle rinse material for HPV DNA testing by Hybrid Capture 2 molecular testing (HC2) as an alternative to p16 immunohistochemistry. Twenty-two cases of HNSCC presenting with neck lymph node metastasis were prospectively identified by assessment of Diff Quik stained cytology smears. An aliquot of the needle rinse material from the lymph node was analyzed for HPV status using standard HC2 protocol. P16 status was determined with immunohistochemistry on the cell block and/or surgically obtained tumor. The mean age of patients with p16 negative HNSCC was 7 years older than p16 positive disease (Table ). Primary tumor subsites were as follows: 17 oropharynx, 1 hypophayrnx, 3 larynx, and 1 oral cavity (Table ). All ten p16 negative patients had a history of smoking compared with 33% of p16 positive. Only 3 (25%) of p16 positive tumors demonstrated keratinization, whereas 90% of the p16 negative tumors keratinized (Fig. 1). Twelve of 22 HNSCC cases (55%) were p16 positive, of which 7 (58%) tested positive for HPV by HC2. Ten cases (45%) were negative for p16, all of which were negative for HPV by HC2 (Table ). Molecular testing for HPV using HC2 on needle rinse material of FNA of HNSCC is a useful method of determining HPV status in HNSCC. Diagn. Cytopathol. 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Diagnostic Cytopathology 10/2014; 3(5). DOI:10.1016/j.jasc.2014.09.107 · 1.52 Impact Factor
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    ABSTRACT: Context .- Global proteomic analysis of oral cavity squamous cell carcinoma was performed to identify changes that reflect patient outcomes. Objectives .- To identify differentially expressed proteins associated with patient outcomes and to explore the use of imaging mass spectrometry as a clinical tool to identify clinically relevant proteins. Design .- Two-dimensional separation of digested peptides generated from 43 specimens with high-resolution mass spectrometry identified proteins associated with disease-specific death, distant metastasis, and loco-regional recurrence. RNA expressions had been correlated to protein levels to test transcriptional regulation of clinically relevant proteins. Imaging mass spectrometry explored an alternative platform for assessing clinically relevant proteins that would complement surgical pathologic diagnosis. Results .- Seventy-two peptide features were found to be associated with 3 patient outcomes: disease-specific death (9), distant metastasis (16), and loco-regional recurrence (39); 8 of them were associated with multiple outcomes. Functional ontology revealed major changes in cell adhesion and calcium binding. Thirteen RNAs showed strong correlation with their encoded proteins, implying transcriptional control. Reduction of DSP, PKP1, and TRIM29 was associated with significantly shorter time to onset of distant metastasis. Reduction of PKP1 and TRIM29 correlated with poorer disease-specific survival. Additionally, S100A8 and S100A9 reductions were verified for their association with poor prognosis using imaging mass spectrometry, a platform more adaptable for use with surgical pathology. Conclusions .- Using global proteomic analysis, we have identified proteins associated with clinical outcomes. The list of clinically relevant proteins observed will provide a means to develop clinical assays for prognosis and optimizing treatment selection.
    Archives of pathology & laboratory medicine 10/2014; 139(4). DOI:10.5858/arpa.2014-0131-OA · 2.88 Impact Factor
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    ABSTRACT: Background. Circumcision and lower human papillomavirus (HPV) viral loads in men are possibly associated with a reduced risk of HPV transmission to women. However, the association between male circumcision and HPV viral load remains unclear. Methods. Swab specimens from the glans and shaft of the penis were collected from men enrolled in a circumcision trial in Kisumu, Kenya. GP5+/6+ polymerase chain reaction (PCR) was used to identify HPV DNA types. HPV-16 and HPV-18 loads were measured with a LightCycler real-time PCR and classified as high (>250 copies/scrape) or low (≤250 copies/scrape). Results. A total of 1159 men were randomly assigned to undergo immediate circumcision, and 1140 men were randomly assigned to the control arm (these individuals were asked to remain uncircumcised until the study ended). The hazard of acquisition of high-viral load infections in the glans was lower in the circumcision arm, compared with the control arm, for HPV-16 (hazard ratio [HR], 0.32 [95% confidence interval {CI}, .20–.49]) and HPV-18 (HR, 0.34 [95% CI, .21–.54]). The 6-month risk of HPV persistence among men with high-viral load infections in the glans at baseline was lower in the circumcision arm, compared with the control arm, for HPV-16 (risk ratio [RR], 0.36 [95% CI, .18–.72]) and HPV-18 (RR 0.34 [95% CI, .13–.86]). Weaker and less precise results were obtained for shaft samples. Conclusions. Male circumcision could potentially reduce the risk of HPV transmission to women by reducing the hazard of acquisition, and the risk of persistence of high-HPV viral load infections in the glans in men.
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    ABSTRACT: Objective: To validate an algorithm for oral health status and compare to overall health. Decayed-Missing-Filled-Teeth (DMFT) scores, oral hygiene and medical co-morbidities provide measures to assess caries risk. Hypotheses: 1. DMFT score should be lower with children and higher with decreased health status. Method: Cohort 1: Children age 1 through 12 years of age; Cohort 2: people with multiple chronic illnesses and living with Human Immunodeficiency Virus (HIV)/Autoimmune deficiency syndrome (AIDS) and other medical comorbidities; Cohort 3: People requiring complex prosthodontic rehabilitation. DMFT scores were measured. The number of medical co-morbidities was measured using the Charlson Comorbidity Index (CCI) and an electronic health record data mining program, Clinical Looking Glass®. Result: The DMFT scores were compared between the three cohorts, with a mean value of 0.695833±0.32 standard deviations (SD). Mean [A] = 0.023±0.018 SD, and 0.012±0.015 SD. DMFT scores varied considerably with age mean T ratio = 0.73±0.96 SD with a median of 0.5 and range of 0.14-7.0. Age and number of comorbidities was positively associated with DMFT although this was not significant (p=0.094). Whereas DMFT score increased with age (p=0.571) and decreased with comorbidities (p=0.772), the small sample size (N=55) and variability in measurements precluded associations from being significant. CCI scores ranged to include 58 co-morbidities in Cohort 2. Conclusion: Further study with increased sample size is required to demonstrate associations and identify predisposition to caries for targeting interventions. Diet, personal oral hygiene, microbiome, fluoride supplementations and/or access to dental care are overwhelming and confounding factors that need to be considered.
    IADR General Session and Exhibition 2014; 06/2014
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    ABSTRACT: Background. Sexually transmitted infections (STIs) are common among adolescents, and multiple STIs over one's lifetime can increase health risks. Few studies have assessed lifetime STI prevalence. This study evaluates minority, underserved adolescents' self-reported lifetime STI history and objective STI rates. Methods. Lifetime STI rates of female patients at an urban adolescent health center were obtained from self-administered questionnaires. Additionally, STI test results were retrieved from electronic medical records. Results. Patients reported a high lifetime prevalence of STIs. By comparing self-report and objective data, underreporting was identified for chlamydia, gonorrhea, and herpes. Conclusions. STI rates in at-risk adolescent females are higher than in the general population and remain elevated over time. Lifetime STI reports could expand our understanding of sexual health and should be further studied. Underreporting, which may increase health risks and hinder health care delivery, requires further investigation. Improvements in STI screening and prevention targeting at-risk populations are warranted.
    Clinical Pediatrics 05/2014; 53(9). DOI:10.1177/0009922814533816 · 1.26 Impact Factor
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    ABSTRACT: Dental services are increasingly recognized as complimentary to medical care and acknowledged as part of the Chronic Care Model (CCM). The Patient Assessment of Chronic Illness Care (PACIC), a validated, primary care assessment instrument is used to measure patient centered outcomes in medical settings. These outcomes include satisfaction with care and whether it aligns with the CCM. We report on the use of the PACIC instrument for assessing dental patient centered outcomes. Objectives: 1) Provide a baseline evaluation of whether patients receive patient-centered, proactive, planned care that includes collaborative goal setting; problem-solving and follow-up support in the dental setting; 2) Assess the validity of using the PACIC survey in dental settings by comparing baseline dental outcomes to baseline medical outcomes, and 3) Use PACIC data to improve dental patient satisfaction with care and outcomes. Methods: During a 3-month period (2012), 563 adults reporting one or more chronic illnesses were randomly selected from approximately 14,500 unique dental patients who received dental care at an urban, inner city academic health center. These adults completed the 20-item PACIC survey, which measures patient activation (items 1-3), delivery system design/decision support (items 4-6), goal setting (items 7-11), problem solving/contextual counseling (items 12-15), and follow-up/coordination of care (items 16-20). PACIC rating consists of a 5-point Likert scale and an overall summary score. Results: We compared the overall summary PACIC scores from the dental patients to those reported in the medical literature. In our survey, baseline mean dental PACIC values ranged from 2.79–3.12 (Standard Deviation (SD) = 0.14) compared to baseline medical range 3.25–3.46 (SD =1.21). Conclusion: The PACIC appears to be a practical, reliable instrument for assessing dental patient satisfaction with care and outcomes. PACIC may be a valuable tool for bringing CCM concepts into the dental setting.
    AADR Annual Meeting & Exhibition 2014; 03/2014
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    ABSTRACT: Clinical research with adolescents can be challenging due to issues of informed consent, parental involvement, institutional review board requirements, and adolescent psychosocial development. These requirements present a dilemma, particularly in the area of sexual health research, as adolescents are disproportionately affected by sexually transmitted infections such as human papillomavirus (HPV). To successfully conduct adolescent research in the clinical setting, one requires an awareness of state statutes regarding adolescent confidentiality and consent for medical care, and a close partnership with the IRB. In 2007, the Mount Sinai Adolescent Health Center in collaboration with the Albert Einstein College of Medicine developed a longitudinal research study to examine the natural history of oral, cervical, and anal HPV in an adolescent female population engaged in high-risk sexual behaviors. We use this research project as a case study to explore the ethical, methodological, and clinical issues related to conducting adolescent health research. Several strategies were identified to promote adolescent study participation, including: (1) building a research team that is motivated to work with adolescents; (2) combining research and patient care visits to avoid duplication of services; and (3) establishing a personalized communication network with participants. Using these methods, adolescent sexual health research can successfully be integrated into the clinical setting. While retaining a prospective cohort of adolescents has its challenges, a persistent and multi-disciplinary approach can help improve recruitment, sustain participation, and acquire critical data that will lead to improved healthcare knowledge applicable to understudied populations of adolescents.
    Journal of pediatric and adolescent gynecology 12/2013; 27(5). DOI:10.1016/j.jpag.2013.08.004 · 1.81 Impact Factor
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    ABSTRACT: Objectives: To develop an algorithm to identify individuals that need targeted fluoride (F) supplementation. Decayed-Missing-Filled-Teeth (DMFT) scores, enamel thickness and fluoride (F) content of teeth, oral hygiene and medical co-morbidities may provide measures to assess caries susceptibility. Hypotheses: 1. DMFT score should be lower with thicker enamel. Rationale: Demineralization requires longer time for caries progression. 2. DMFT score should be lower with higher F content in enamel or dentin. Rationale: F decreases enamel/dentin (E/D) solubility in an acidic cariogenic environment. Methods: Cohort 1: Enamel thickness measurements: Digital radiographs were measured from enamel surface to the DEJ at the Mesial (M) height of contour and calibrated against a standard 5mm ball. F content was determined in powdered enamel and dentin using F-ion selective electrode. DMFT scores were measured. Cohort 2: The number of medical co-morbidities was measured using the Charlson Comorbidity Index (CCI) and an electronic health record data mining program. Results: The enamel thickness ranged from 1.2 to 2.65 mm, with a mean value of 1.63±0.32 standard deviations (SD). Mean [F] = 0.023±0.018 SD for enamel, and 0.012±0.015 SD for dentin. DMFT scores varied considerably with mean T ratio = 0.73±0.96 SD with a median of 0.5 and range of 0.14-7.0. Enamel thickness was positively associated with DMFT although this was not significant (p=0.094). Whereas DMFT score increased with F content in enamel (p=0.571) and decreased with F content in dentin (p=0.772), the small sample size (N=55) and variability in measurements precluded associations from being significant. CCI scores ranged to include 58 co-morbidities in Cohort 2. Conclusion: Further study with increased sample size is required to demonstrate associations and identify predisposition to caries for targeting interventions. Diet, personal oral hygiene, microbiome, fluoride supplementations and/or access to dental care are overwhelming and confounding factors that need to be considered.
    6th AADR Fall Focused Symposium: Personalized Oral Health Care: Concept Design to Clinical Practice 2013; 10/2013
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    ABSTRACT: Recent evidence suggests that human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) patients have better survival than HPV-negative patients. However, it is unclear if similar patterns for survival exist across different tumor sites, and whether HPV-associated prognosis is modified by type of treatment. We prospectively tested 222 histologically confirmed HNSCC primary tumors for HPV DNA by PCR and HPV E6/E7 RNA by RT-PCR prior to treatment at a large urban health center. Cox proportional hazard ratio models were constructed to assess HPV-associated differences in overall and disease-specific survival adjusting for clinical and demographic covariates. HPV detection varied significantly by primary HNSCC tumor site, from 35 % for oropharynx, to 25 % for hypopharynx, 5 % for larynx, and 3 % for oral cavity (p < 0.0001), with HPV16 accounting for the majority (95 %) of HPV-positive tumors. The hazard-risk of overall and disease-specific death comparing HPV16-positive versus negative oropharyngeal HNSCC was reduced by 74 and 89 %, respectively (p values < 0.05), and was independent of other prognostic indicators; no statistically significant changes in outcomes were observed for non-oropharyngeal HNSCC sites. Prediction of overall survival was better with combined DNA and RNA HPV16 positive PCR detection. There was no difference in HPV16-associated survival whether patients received either surgery or (chemo)radiotherapy as their initial treatment modality. Improved HPV-associated HNSCC survival is limited to patients with oropharyngeal primaries. No selective treatment advantage is observed for HPV-positive tumors, although clinical trials are needed to evaluate which treatment modalities provide the most benefit for HPV-positive HNSCC.
    Head and Neck Pathology 09/2013; 8(1). DOI:10.1007/s12105-013-0486-4
  • Cancer Research 08/2013; 73(8 Supplement):4939-4939. DOI:10.1158/1538-7445.AM2013-4939 · 9.28 Impact Factor
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    ABSTRACT: We have utilized a genome-wide approach to identify novel differentially methylated CpG dinucleotides that are seen in different anatomic sites of head and neck squamous cell carcinoma (HNSCC), as well as those that might be related to HPV status in the oropharynx. We performed genome-wide DNA methylation profiling of primary tumor samples and corresponding adjacent mucosa from 118 HNSCC patients undergoing treatment at Montefiore Medical Center, Bronx, NY using the Illumina HumanMethylation27 beadchip. For each matched tissue set, we measured differentially methylated CpG loci using a change in methylation level (M-value). When datasets were individually analyzed by anatomic site of the primary tumor, we identified 293 differentially methylated CpG loci in oral cavity SCC, 219 differentially methylated CpG loci in laryngeal SCC, and 460 differentially methylated in oropharyngeal SCC. A subset of these differentially methylated CpG loci was common across all anatomic sites of HNSCC. Stratification by HPV status revealed a significantly higher number of differentially methylated CpG loci in HPV-positive patients. Novel epigenetic biomarkers derived from clinical HNSCC specimens can be used molecular classifiers of this disease, revealing many new avenues of investigation for this disease.
    Clinical Cancer Research 07/2013; 19(19). DOI:10.1158/1078-0432.CCR-12-3280 · 8.19 Impact Factor

Publication Stats

2k Citations
275.51 Total Impact Points


  • 2005–2015
    • Albert Einstein College of Medicine
      • • Department of Epidemiology & Population Health
      • • Department of Pathology
      • • Oncology
      New York, New York, United States
    • University of California, San Francisco
      San Francisco, California, United States
  • 1998–2013
    • McGill University
      • Department of Oncology
      Montréal, Quebec, Canada
  • 2012
    • Albert Einstein Medical Center
      Philadelphia, Pennsylvania, United States
  • 2011–2012
    • Montefiore Medical Center
      • Albert Einstein College of Medicine
      New York City, New York, United States
  • 2000
    • Ludwig Institute for Cancer Research Brazil
      San Paulo, São Paulo, Brazil