Combined analysis of HPV DNA, p16, p21 and p53 to predict prognosis in patients with stage IV hypopharyngeal carcinoma

We examined p16, p21 and p53 expression in combination with the presence of human papillomavirus (HPV) DNA as molecular markers to predict survival in patients with stage IV hypopharyngeal squamous cell carcinoma (HSCC).Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

HPV-Related Nonkeratinizing Squamous Cell Carcinoma of the Oropharynx: Utility of Microscopic Features in Predicting Patient Outcome

Human papilloma virus (HPV) is an etiologic agent in a subset of oropharyngeal squamous cell carcinomas (SCCs). The aim of this study was to sub-classify SCC of the oropharynx based upon histologic features into nonkeratinizing (NK) SCC, keratinizing (K) SCC, and hybrid SCC, and determine the frequency of HPV and patient survival in each group. Patients with oropharyngeal SCC with a minimum of 2 years of clinical follow-up were identified from radiation oncology databases from 1997 to 2004. All patients received either up front surgery with postoperative radiation or definitive radiation based therapy. In situ hybridization (ISH) for high-risk HPV subtypes and immunohistochemistry for p16, a protein frequently up-regulated in HPV-associated carcinomas, were performed. Overall and disease-specific survival were assessed. Of 118 cases, 46.6% were NK SCC, 24.6% K SCC and 28.8% hybrid SCC. NK SCC occurred in slightly younger patients that were more often male. It more frequently presented with lymph node metastases and was surgically resected compared to K SCC. NK SCC was significantly more likely to be HPV and p16 positive than KSCC (P < 0.001) and to have better overall and disease-specific survival (P = 0.0002; P = 0.0142, respectively). Hybrid SCC was also more likely than K SCC to be HPV and p16 positive (P = 0.003; P = 0.002, respectively) and to have better overall survival (P = 0.0105). Sub-classification of oropharyngeal SCC by histologic type provides useful clinical information. NK SCC histology strongly predicts HPV-association and better patient survival compared to K SCC. Hybrid SCC appears to have an intermediate frequency of HPV-association and patient survival

Mammalian cell entry genes in Streptomyces may provide clues to the evolution of bacterial virulence

Understanding the evolution of virulence is key to appreciating the role specific loci play in pathogenicity. Streptomyces species are generally non-pathogenic soil saprophytes, yet within their genome we can find homologues of virulence loci. One example of this is the mammalian cell entry (mce) locus, which has been characterised in Mycobacterium tuberculosis. To investigate the role in Streptomyces we deleted the mce locus and studied its impact on cell survival, morphology and interaction with other soil organisms. Disruption of the mce cluster resulted in virulence towards amoebae (Acanthamoeba polyphaga) and reduced colonization of plant (Arabidopsis) models, indicating these genes may play an important role in Streptomyces survival in the environment. Our data suggest that loss of mce in Streptomyces spp. may have profound effects on survival in a competitive soil environment, and provides insight in to the evolution and selection of these genes as virulence factors in related pathogenic organisms

Salivary Markers for Oral Cancer Detection

Oral cancer refers to all malignancies that arise in the oral cavity, lips and pharynx, with 90% of all oral cancers being oral squamous cell carcinoma. Despite the recent treatment advances, oral cancer is reported as having one of the highest mortality ratios amongst other malignancies and this can much be attributed to the late diagnosis of the disease. Saliva has long been tested as a valuable tool for drug monitoring and the diagnosis systemic diseases among which oral cancer. The new emerging technologies in molecular biology have enabled the discovery of new molecular markers (DNA, RNA and protein markers) for oral cancer diagnosis and surveillance which are discussed in the current review

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Hispanic health in the USA: a scoping review of the literature

Hispanics are the largest minority group in the USA. They contribute to the economy, cultural diversity, and health of the nation. Assessing their health status and health needs is key to inform health policy formulation and program implementation. To this end, we conducted a scoping review of the literature and national statistics on Hispanic health in the USA using a modified social-ecological framework that includes social determinants of health, health disparities, risk factors, and health services, as they shape the leading causes of morbidity and mortality. These social, environmental, and biological forces have modified the epidemiologic profile of Hispanics in the USA, with cancer being the leading cause of mortality, followed by cardiovascular diseases and unintentional injuries. Implementation of the Affordable Care Act has resulted in improved access to health services for Hispanics, but challenges remain due to limited cultural sensitivity, health literacy, and a shortage of Hispanic health care providers. Acculturation barriers and underinsured or uninsured status remain as major obstacles to health care access. Advantageous health outcomes from the “Hispanic Mortality Paradox” and the “Latina Birth Outcomes Paradox” persist, but health gains may be offset in the future by increasing rates of obesity and diabetes. Recommendations focus on the adoption of the Health in All Policies framework, expanding access to health care, developing cultural sensitivity in the health care workforce, and generating and disseminating research findings on Hispanic health