HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management.

Human papillomavirus (HPV)-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The most recent (8th) edition of the UICC/AJCC staging system separates HPV+ OPSCC from its HPV-negative (HPV-) counterpart to account for the improved prognosis seen in the former. Indeed, owing to its improved prognosis and greater prevalence in younger individuals, numerous ongoing trials are examining the potential for treatment de-intensification as a means to improve quality of life while maintaining acceptable survival outcomes. In addition, owing to the distinct biology of HPV+ OPSCCs, targeted therapies and immunotherapies have become an area of particular interest. Importantly, OPSCC is often detected at an advanced stage owing to a lack of symptoms in the early stages; therefore, a need exists to identify and validate possible diagnostic biomarkers to aid in earlier detection. In this Review, we provide a summary of the epidemiology, molecular biology and clinical management of HPV+ OPSCC in an effort to highlight important advances in the field. Ultimately, a need exists for improved understanding of the molecular basis and clinical course of this disease to guide efforts towards early detection and precision care, and to improve patient outcomes

Evidence for lung epithelial stem cell niches

Recent studies have identified epithelial stem and progenitor cell populations of the lung. We are just beginning to understand the mechanisms that regulate their homeostatic, regenerative and maladaptive behaviors. Here, we discuss evidence of regulatory niches for epithelial stem cells of the lung

Sinonasal Cancer: Improving Classification, Stratification and Therapeutic Options

: The nasal cavities and paranasal sinuses are the site of origin of a wide spectrum of histologically and clinically distinct disease entities [...]

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution

Bulk-tissue DNA methylomes represent an average over many different cell types, hampering our understanding of cell-type-specific contributions to disease development. As single-cell methylomics is not scalable to large cohorts of individuals, cost-effective computational solutions are needed, yet current methods are limited to tissues such as blood. Here we leverage the high-resolution nature of tissue-specific single-cell RNA-sequencing datasets to construct a DNA methylation atlas defined for 13 solid tissue types and 40 cell types. We comprehensively validate this atlas in independent bulk and single-nucleus DNA methylation datasets. We demonstrate that it correctly predicts the cell of origin of diverse cancer types and discovers new prognostic associations in olfactory neuroblastoma and stage 2 melanoma. In brain, the atlas predicts a neuronal origin for schizophrenia, with neuron-specific differential DNA methylation enriched for corresponding genome-wide association study risk loci. In summary, the DNA methylation atlas enables the decomposition of 13 different human tissue types at a high cellular resolution, paving the way for an improved interpretation of epigenetic data

Anosmia as a presenting symptom of SARS-CoV-2 infection in healthcare workers – A systematic review of the literature, case series, and recommendations for clinical assessment and management

Background: Healthcare workers are at the forefront of the ongoing COVID-19 pandemic and are at high risk for both the contraction and subsequent spread of virus. Understanding the role of anosmia as an early symptom of infection may improve monitoring and management of SARS-CoV2 infection. Methodology: We conducted a systematic review of the literature of SARS-CoV2 infection/COVID-19 and anosmia to help inform management of anosmia in healthcare works. We report a case series of healthcare workers, who presented with a loss of sense of smell secondary to COVID-19 infection to demonstrate management principles. RT-PCR was used to confirm COVID-19 positivity and psychophysical testing of olfaction was performed using the British version of the University of Pennsylvania Smell Identification Test, UPSIT. Results: The systematic literature search returned 31 articles eligible for inclusion in the study and informed our recommendations for clinical assessment and management. All three healthcare professionals who presented with loss of sense of smell subsequently tested positive for SARS-CoV-2. Psychophysical testing of olfaction using the UPSIT confirmed mild and moderate microsmia in two, respectively, and normosmia at day 17 in one. Conclusions: Olfactory (± gustatory) dysfunction is indicative of COVID-19 infection and thus has important implications in the context of healthcare workers, or key workers in general, who work in close contact with others if not recognised as suffering from COVID. This leads to a potentially higher likelihood of spreading the virus. In conjunction with our literature review these findings have helped with creating recommendations on the assessment and management of olfactory dysfunction during the ongoing COVID-19 pandemic, both for healthcare workers and patients

Standardized List Evaluating Apnea (SLEAP): A Comprehensive Survey to Define the Quality of Life in OSA

OBJECTIVE: To develop and validate a patient-reported outcome measure (PROM) to evaluate the quality of life (QoL) among patients with obstructive sleep apnea (OSA). STUDY DESIGN: A prospective cohort study. SETTINGS: Tertiary referral center. METHODS: We developed a 15-item English questionnaire that was administered to 176 adults with OSA and 22 adult controls without symptoms of OSA in a tertiary sleep surgery clinic between June 2021 and December 2021. The internal consistency and test-retest reliability were measured using the Cronbach's α and the intraclass correlation coefficient, respectively. The 2-sample Wilcoxon rank-sum (Mann-Whitney) test was applied to compare the 2 groups. Convergent validity of the test scores of the questionnaire was compared to previously validated outcome measures and objective sleep study outcomes using the Spearman correlation coefficient. RESULTS: Of the 198 respondents (176 cases and 22 controls); 71% were men and 29% were women. The internal consistency was excellent with the α of .92 (lower 95% confidence limit of 0.90). All the test-retest correlations were positive, significant, and strong ranging from 0.50 to 0.90. The differences between cases and controls were statistically significant for all the items and for the total score. The total score of the questionnaire with the Epworth Sleepiness Scale and objective OSA measures was moderate to strong. CONCLUSIONS AND RELEVANCE: The new tool provides a validated PROM to evaluate the QoL among OSA patients specifically, with excellent internal consistency, reasonable test-retest reliability, discriminant validity, and construct validity. LEVEL OF EVIDENCE: Level 4