Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma

We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P < 0.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05-0.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC

Acquisition and Persistence of Human Papillomavirus 16 (HPV-16) and HPV-18 Among Men With High-HPV Viral Load Infections in a Circumcision Trial in Kisumu, Kenya

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

Cervical, Anal and Oral HPV in an Adolescent Inner-City Health Clinic Providing Free Vaccinations

Published human papillomavirus (HPV) vaccine trials indicate efficacy is strongest for those naive to the vaccine-types. However, few high-risk young women have been followed and cervical HPV has been the predominant outcome measure.We collected cervical and anal swabs, as well as oral rinse specimens from 645 sexually active inner-city young females attending a large adolescent health-clinic in New York City that offers free care and HPV vaccination. Specimens were tested for HPV-DNA using a MY09/MY11-PCR system. Type-specific prevalence of HPV at each anatomic site was compared for individuals by vaccination dose using generalized estimating equation logistic regression models.The majority of subjects reported being of non-Caucasian (92%) and/or Hispanic ethnicity (61%). Median age was 18 years (range:14-20). All had practiced vaginal sex, a third (33%) practiced anal sex, and most (77%) had also engaged in oral sex. At enrollment, 21% had not received the vaccine and 51% had received three doses. Prevalent HPV infection at enrollment was detected in 54% of cervical, 42% of anal and 20% of oral specimens, with vaccine types present in 7%, 6% and 1% of specimens, respectively. Comparing prevalence for vaccine types, the detection of HPV in the cervix of vaccinated compared to unvaccinated adolescents was significantly reduced: HPV6/11 (odds ratio [OR] = 0.19, 95%CI:0.06-0.75), HPV16 (OR = 0.31, 95%CI:0.11-0.88) and HPV18 (OR = 0.14, 95%CI:0.03-0.75). For anal HPV, the risk of detecting vaccine types HPV6/11 (OR = 0.27, 95%CI:0.10-0.72) and HPV18(OR = 0.12, 95%CI:0.01-1.16) were significantly reduced for vaccinated adolescents however, the risk for HPV16 was not significantly decreased (OR = 0.63, 95%CI:0.18-2.20).HPV Prevalence is extremely high in inner-city female adolescents. Administration of the HPV vaccine reduced the risk for cervical HPV; however continued follow-up is required to assess the protection for HPV at all sites in young women with high exposure

Physiological and psychosocial determinants of health-care service utilisation in chronic obstructive pulmonary disease patients

Introduction. There is evidence that psychosocial factors and social support are determinants of health-related quality of life (HRQoL) and health-care services use in patients with chronic diseases. Objective . To evaluate what physiological, psychosocial or HRQoL factors are predictors of health-care services use in COPD. Methods. A combination retrospective/prospective hospital-based cohort study was designed. 90 patients with stable COPD were selected from an out-patient registry at the Montreal Chest Institute. Patient evaluation included an interview with two disease specific HRQoL questionnaires: St. George's Respiratory Questionnaire and Chronic Respiratory Questionnaire; and five psychosocial questionnaires: Coping Inventory for Stressful Situations, State/Trait Anxiety Inventory, Beck Depression Index, NEO Five Factor Personality Inventory, and Interpersonal Relationships Inventory. Physiological measurements and symptom evaluation included spirometry, six-minute walking tests, and the American Thoracic Society Lung Disease Questionnaire (ATS-DLD-78). Outcome. Emergency room visits, return visits to the ER, and overnight hospitalisations were collected from patients' medical charts. Results. Independent associations were observed for age, gender, lung function, six-minute walking test distance, and use of oral cortico-steroids. HRQoL measures also demonstrated an ability to predict health-care service outcomes. Multivariate model selection identified disease severity and HRQoL as the strongest correlates of presentation for an emergency visit in COPD patients

Human Papillomavirus Vaccination in Pediatric, Adolescent, and Young Adult Cancer Survivors—Opportunity to Address Gaps in Cancer Prevention and Survivorship

The risks of secondary cancers associated with human papillomavirus (HPV) infection are as much as three times higher for survivors of pediatric, adolescent, and young adult cancer (PYAC) compared to the general population. Despite this, HPV vaccination rates among PYAC survivors remain low. Whereas pediatric oncology providers endorse HPV vaccination of PYAC survivors, many lack the resources or opportunities to intervene. The responsibility of HPV vaccination, therefore, falls to primary care providers and practices. This article provides an overview of the challenges with HPV vaccination that are distinct to PYAC survivors and discusses potential strategies to increase HPV vaccine coverage in this population

Feldversuchsinfrastrukturen – Status quo und Perspektiven. Positionspapier der DFG Senatskommission für Agrarökosystemforschung

Groß angelegte und langfristig etablierte Feldversuche sind ein zentrales Element der standortbezogenen Agrarwissenschaften. Die Erarbeitung des Grundlagenwissens zu standortangepassten bzw. regional spezifischen Produktivitätspotentialen von Pflanzenbeständen sowie die Entwicklung von ökologisch vertretbaren, innovativen Produktionssystemen mit hoher Produktivität und Resi­lienz erfordern leistungsfähige Forschungsinfrastrukturen, die relevante Gradienten an Klima- und Bodenfaktoren abdecken und den interdisziplinären Dialog fördern. Das Positionspapier der Senatskommission für Agrar­öko­systemforschung der Deutschen Forschungsgemeinschaft stellt den Status quo und die zukünftigen Anforderungen an Feldversuchseinrichtungen dar. Zur Optimierung des agrarwissenschaftlichen Feldversuchswesens wird angeregt, in einem Netzwerk aus Versuchseinrichtungen Landschaftsfunktionen prototypisch abzubilden, um in einem interdisziplinären Ansatz Flächenproduktivität, Resilienz und Ressourceneffizienz landschaftsspezifisch untersuchen zu können. Des Weiteren ist es erforderlich, der wissenschaftlichen Community standardisierte Daten in Datenrepositorienzur Verfügung zu stellen

Human papillomavirus genotypes and risk of head and neck cancers: Results from the HeNCe Life case-control study

International audienceOBJECTIVE:Human papillomaviruses (HPV) are changing dramatically the epidemiologic landscape of head and neck cancers (HNCs). Their role in the aetiology of these cancers varies widely among HNCs subsites, sex and geographical regions worldwide. We describe HPV prevalence and its association with HNCs risk overall and by anatomical subsite in a sample of Canadians.MATERIALS AND METHODS:The HeNCe Life study recruited 460 incident HNCs cases and 458 controls frequency-matched by age and sex from four Montreal hospitals in 2005-2013. We tested oral rinse and oral brush specimens for mucosal HPV genotypes. HPV positivity was categorized hierarchically as either negative, exclusively non-α-9 species types, α-9 types other than HPV16, and HPV16. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the associations between HPV and HNCs using unconditional logistic regression, controlling for confounders.RESULTS:The prevalence of HPV infection among controls and cases was 14.5% and 41.2% in oral rinse and 3.1% and 24.4% in oral brush samples, respectively. HPV16 was the predominant genotype with an oral rinse and oral brush prevalence of 26.3% and 16.2% among cases and 2.4% and 0.2% among controls, respectively. HPV infection was associated with an increased risk of HNCs overall (OR=4.18; 95% CI, 2.94-5.95) and oropharyngeal cancer only (OR=10.3; 95% CI, 6.8-15.7). HNCs and oropharyngeal cancer were strongly associated with HPV16 (OR=18.1; 95% CI, 9.1-35.8, and OR=47.2; 95% CI, 23.1-96.6, respectively).CONCLUSION:HPV infection, particularly HPV16, was associated with an increased HNCs risk, most strongly for oropharyngeal cancers