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Amalie Hartvig Pall,1 Anne Fog Lomholt,1 Christian von Buchwald,1 Anette Bygum,2– 4 Eva Rye Rasmussen1,2 1Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark; 2OPEN – Open Patient Data Explorative Network, Odense University Hospital, Odense, Denmark; 3Department of Dermatology and Allergy Centre, Odense University Hospital, Odense 5000, Denmark; 4Department of Clinical Research, University of Southern Denmark, Odense 5000, DenmarkCorrespondence: Amalie Hartvig PallDepartment of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9B, Copenhagen 2100, DenmarkEmail amalie.hartvig.pall.03@regionh.dkPurpose: To give a better understanding of primary AE, the clinical characteristics and the possible therapeutic approaches.Background: Angioedema (AE) is a non-pitting, non-itching swelling of skin or mucosa. The symptom can become life-threatening if located in the airways. Primary (monosymptomatic) AE is a manifestation of several different diseases and the diagnosis is not always straight-forward. The aetiological and pathophysiological factors of primary AE are not completely clarified. There is a need for further investigation.Patients and Methods: This was a retrospective cohort study of patients referred to an outpatient dermatology clinic in a tertiary care hospital for clinical assessment due to primary AE in the period from 1996 to 2014.Results: A total of 315 patients were identified with primary AE. The most frequent subtype was idiopathic AE (42.5%) and the second most common was angiotensin-converting enzymeinhibitor (ACEi)-induced AE (31.1%). Three patients were diagnosed with hereditary AE and one patient was diagnosed with acquired C1-inhibitor deficiency. At least 107 (34.0%) patients had established histaminergic AE. More than 1/3 of the patients were treated in an emergency room or hospitalized due to AE. A 98.1% of patients had experienced AE in the head and neck area. Seven patients were in the need of acute airway intervention. Six of these had ACEi-induced AE. Female sex and smoking were found to be risk factors for developing AE.Conclusion: The most frequent diagnoses were histaminergic-, non-histaminergic idiopathic AE and ACEi-induced AE, whereas complement C1-inhibitor deficiency was rare. Histaminergic AE made up a substantial group of patients with primary AE. Even though there are different pathophysiological causes of AE, many cases have overlapping clinical manifestations, which make diagnosis and treatment difficult.Keywords: primary angioedema, urticaria, hereditary angioedema, angiotensin-converting enzyme inhibitors, bradykinin

Jakob Schmidt Jensen,1 Kathrine Kronberg Jakobsen,1 Christian Mirian,1 Julie Thor Christensen,1 Katrine Schneider,1 Arvin Nahavandipour,1 Vibe Lindeblad Wingstrand,1 Irene Wessel,1 Jesper Filtenborg Tvedskov,1 Thomas Frisch,1 Anders Christensen,1 Lena Specht,2 Elo Andersen,3 Giedrius Lelkaitis,4 Christian Grønhøj,1 Christian von Buchwald11Department of Otorhinolaryngology, Head and Neck Surgery, and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark; 2Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark; 3Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev 2730, Denmark; 4Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, DenmarkCorrespondence: Christian von BuchwaldDepartment of Otorhinolaryngology, Head and Neck Surgery, and Audiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen 2100, DenmarkTel +45 3 545 2370Email Christian.von.buchwald@regionh.dkObjective: The aim was to establish a large comprehensive database of patients with oral cavity squamous cell carcinoma (OSCC) to enable surveillance and research of the disease.Methods: All patients diagnosed and/or treated for OSCC at Rigshospitalet, University of Copenhagen, Denmark in the period 2000–2014 were included. Rigshospitalet is a tertiary treatment center and covers the Eastern Denmark region, comprising nearly half of the approximately 5.8 million inhabitants of Denmark. Data on numerous variables regarding general information of the patients at diagnosis, their primary cancer, recurrence, treatment, prior cancers, and secondary cancers were collected from the Danish Pathology Register and by evaluation of medical charts.Results: One thousand three hundred and ninety-nine OSCC patients were included in the database (62% males). The median age at diagnosis was 63 years (range: 23–99 years). The most common anatomical location was the floor of mouth (38%). Among patients with known stage, 70.0% were diagnosed in T-stage 1 or 2 and 64.9% were diagnosed in N-stage 0. Most patients were treated with primary surgery (81.7% among patients with known treatment), of these 44% received adjuvant radiotherapy after surgery. The overall age-standardized incidence of OSCC per 100,000 increased from 2.15 in 2000 to 3.04 in 2014, with a significant annual percent change of 3.2%.Conclusion: We have established a consecutive, population-based database of 1,399 OSCC patients. This creates a basis for multiple studies that will elaborate our understanding of OSCC, and hopefully improve diagnosis, treatment, and rehabilitation of OSCC patients.Keywords: head and neck cancer, oral cavity cancer, squamous cell carcinoma, OSCC, database, epidemiology

Subsurface nutrients on the Scotian Shelf, an ocean region at the convergence of the subpolar and subtropical western boundary currents (i.e., Labrador Current (LC) and Gulf Stream (GS)), are chiefly modulated by upstream shelf and slope waters. Yet little is known about long‐term fluctuations in the advective transport of nutrients to the shelf. Here, we synthesized nutrient and hydrographic data from 1975 to 2020 to characterize decadal changes in upper (60–150 m) and lower (150–200 m) subsurface nutrient availability across the shelf. Hydrographic and nutrient anomalies highlight a transition from a warm, saline, high‐nutrient GS‐dominated system in the 1980 to colder, fresher, lower‐nutrient LC‐dominated conditions in the late 1980 and early 1990. In the mid‐1990, an increase in excess silicate and phosphate (relative to nitrate) marks a shift in the LC contribution toward a strengthening of the inner shelf component relative to the outer shelf‐edge branch. Since 2010, rapid increases in subsurface temperature and salinity indicate the transition back to a GS‐dominated system, albeit with a distinct decline in dissolved nutrients relative to the previous warm period, which diverges from the nutrient increase generally associated with GS water. Declines in lower subsurface nutrient concentrations since 2010 are likely driven by a density‐related shift in the GS source water toward a less dense, lower‐nutrient GS contribution. This shift is evidenced by a decrease in excess phosphate amidst minor declines in excess silicate, reflecting the characteristic density‐related patterns of excess nutrients in GS waters. Plain Language Summary: The Northwest Atlantic continental shelf is a highly productive region, sustaining large ecologically and commercially important fisheries from the Grand Banks across the Scotian Shelf into the Gulf of Maine. This high productivity depends on the supply of bioavailable nutrients, which are essential components feeding phytoplankton growth and ecosystem productivity. On the Scotian Shelf, surface productivity is thought to be fueled by the vertical supply of nutrient‐rich subsurface water, deriving from upstream coastal waters, and the onshore transport of deeper slope waters. In this study, we used hydrographic and nutrient data from 1975 to 2020 to investigate long‐term trends in nutrient availability on the shelf. We show that over the past 45 years, subsurface properties have shifted from warm, salty, nutrient‐rich waters at the beginning of the time series to colder, fresher, lower‐nutrient conditions in the 1990/early 2000, and back to warm, salty, yet nutrient‐poor conditions after 2010 due to changes in the dominant source water advected onto the shelf. The significant decline in nutrients since 2010 suggests a shift to a less dense, lower‐nutrient source from the Gulf Stream compared to the previous warm period. Key Points: Subsurface nutrients on the shelf are modulated by advection of upstream coastal water, and offshore Gulf Stream and Labrador Slope WaterNutrient properties indicate a shift in Labrador Current contributions, with a strengthening of the inner versus outer branch in 1995–2010Enhanced contributions from lower‐density Gulf Stream water drive a warming and decrease in subsurface nutrient concentrations since 2010 [ABSTRACT FROM AUTHOR]

Objective: Chronic suppurative otitis media is a major cause of disabling childhood hearing loss, especially in low-income countries. Estimates on its prevalence in sub-Saharan Africa range from the lowest to the highest in the world (less than one per cent to more than five per cent). However, the prevalence of chronic suppurative otitis media in Zimbabwe is largely unknown. This study aimed to determine the prevalence of paediatric chronic suppurative otitis media and other middle-ear pathology in rural Zimbabwe. Method: A cross-sectional study was performed in primary school children aged 4–13 years from the rural province of Mashonaland East. Participants underwent video otoscopy and tympanometry. Results: Out of 451 examined children, two (0.4 per cent) had chronic suppurative otitis media. Acute otitis media was present in one (0.2 per cent), otitis media with effusion was present in five (1.1 per cent) and scarring was present in 69 (15.3 per cent). Conclusion: Chronic suppurative otitis media and otitis media sequelae were surprisingly uncommon in this sample of rural primary school children in Zimbabwe. More studies, preferably population-based, are needed to enable more precise estimates of chronic suppurative otitis media prevalence in Zimbabwe. [ABSTRACT FROM AUTHOR]

Purpose: Patients who have received irradiation therapy on the head and neck area are known to suffer from reduced saliva flow and may therefore use acidic candies to relieve symptoms of dry mouth. However, such acidic candies have erosive potential even among healthy individuals. Therefore, the aim of the present study was to determine if calcium-modified acidic candies have reduced erosive potential in irradiated cancer patients.Materials and Methods: Nineteen cancer patients (26 to 70 years) ipsilaterally irradiated on the head and neck area sucked control and calcium-modified acidic candies, while their whole saliva was collected into a closed system. The erosive potential of both candies was evaluated from saliva degree of saturation with respect to hydroxyapatite and by dissolution of hydroxyapatite (HAp) directly in candy-stimulated saliva. The results were compared to normative data that were previously obtained on 20 healthy test persons (21 to 29 years).Results: No significant difference was obtained in the saliva flow rates between control and calcium-modified candy. However, the saliva became significantly less undersaturated with respect to HAp when sucking calcium-modified compared to control candy (P < 0.001) and more undersaturated for both candies in ipsilaterally irradiated cancer patients compared to normative data (P < 0.001). HAp dissolution was found to be significantly lower in patients sucking the modified candy compared to the control candy (P < 0.01) and, surprisingly, slightly lower in patients compared to normative data.Conclusions: Modified acidic candy with calcium has reduced erosive potential in patients irradiated on the head and neck area and could therefore be used as a favourable stimulant for relief of dry mouth. [ABSTRACT FROM AUTHOR]

Little is known about the nature of microbial community activity contributing to the cycling of nitrogen in organic‐poor sediments underlying the expansive oligotrophic ocean gyres. Here we use pore water concentrations and stable N and O isotope measurements of nitrate and nitrite to constrain rates of nitrogen cycling processes over a 34‐m profile from the deep North Atlantic spanning fully oxic to anoxic conditions. Using a 1‐D reaction‐diffusion model to predict the distribution of nitrogen cycling rates, results converge on two distinct scenarios: (1) an exceptionally high degree of coupling between nitrite oxidation and nitrate reduction near the top of the anoxic zone or (2) an unusually large N isotope effect (~60‰) for nitrate reduction that is decoupled from the corresponding O isotope effect, which is possibly explained by enzyme‐level interconversion between nitrite and nitrate. Key Points: N and O stable isotope profiles reflect a combination of nitrogen cycling processes in deep‐sea sedimentsReaction‐diffusion modeling suggests an unusual dynamic between N isotopes of NO3‐ and NO2‐, with a number of possible mechanisms discussed [ABSTRACT FROM AUTHOR]

Background: The incidence of human papillomavirus‐induced (HPV+) head and neck squamous cell carcinoma (HNSCC), that is, especially oropharyngeal cancers (OPSCC), is increasing, and a significant proportion of patients encounter disease progression. A simple and sensitive test to identify patients with progression is an unmet need. Objective of Review: To systematically review the literature and carry out a meta‐analysis of studies, investigating circulating HPV‐DNA as a biomarker for disease progression in patients with HNSCC. Type of Review: A systematic review and meta‐analysis. Search Strategy: PubMed, EMBASE and the Cochrane Library were systematically searched for articles published in English from January 1980 to November 2017. Search terms used were related to HPV, cancer sites, blood‐based biomarkers and terms for specific use settings. Evaluation Method: Articles reviewed and selected by authors and data on study design, demographic variables, location, HPV status, number of pre‐treatment blood tests, number of post‐treatment blood tests, blood HPV status and number of recurrences and length of follow‐up were extracted. A meta‐analysis of HPV‐DNA as a diagnostic test for recurrence by means of a hierarchical summary receiver operating curve (HSROC) model was performed. Results: We identified 5 studies (n = 600 subjects) examining circulating HPV‐DNA in patients with HNSCC. In these 5 studies (n = 411), patients had both pre‐ and post‐treatment blood samples. The pooled sensitivity, in detecting a recurrence, was estimated to be 54% (95% CI: 32%‐74%), while the pooled specificity was 98% (95% CI: 93%‐99.4%). The pooled false‐positive rate is 2% (95% CI: 0.6%‐7%). The area under the curve (AUC) of the summary HSROC was 0.93. Positive predictive value was estimated to 93% and the negative predictive value to 94%. Conclusions: Plasma HPV‐DNA is a promising tool for surveillance in patients with HPV‐related HNSCC, that is, OPSCC, and has a high specificity. By recent technical advances and by increasing follow‐up blood samples, the sensitivity could likely be improved. [ABSTRACT FROM AUTHOR]

Background:In developing countries with limited access to ENT services, performing emergency cricothyroidotomy in patients with upper airway obstruction may be a life-saving last resort. An established Danish–Zimbabwean collaboration of otorhinolaryngologists enrolled Zimbabwean doctors into a video-guided simulation training programme on emergency cricothyroidotomy. This paper presents the positive effect of this training, illustrated by two case reports.Case reports:A 56-year-old female presented with upper airway obstruction due to a rapidly progressing infectious swelling of the head and neck progressing to cardiac arrest. Cardiopulmonary resuscitation was initiated and a secure surgical airway was established via an emergency cricothyroidotomy, saving the patient. A 70-year-old male presented with upper airway obstruction secondary to intubation for an elective procedure. When extubated, the patient exhibited severe stridor followed by respiratory arrest. Re-intubation attempts were unsuccessful and emergency cricothyroidotomy was performed to secure the airway, preserving the life of the patient.Conclusion:Emergency cricothyroidotomy training should be considered for all surgeons, anaesthetists and, eventually, emergency and recovery room personnel in developing countries. A video-guided simulation training programme on emergency cricothyroidotomy in Zimbabwe proved its value in this regard. [ABSTRACT FROM PUBLISHER]

Nitrogen (N) is a key component of fundamental biomolecules. Hence, its cycling and availability are central factors governing the extent of ecosystems across the Earth. In the organic-lean sediment porewaters underlying the oligotrophic ocean, where low levels of microbial activity persist despite limited organic matter delivery from overlying water, the extent and modes of nitrogen transformations have not been widely investigated. Here we use the N and oxygen (O) isotopic composition of porewater nitrate (NO3-/from a site in the oligotrophic North Atlantic (Integrated Ocean Drilling Program - IODP) to determine the extent and magnitude of microbial nitrate production (via nitrification) and consumption (via denitrification). We find that NO3- accumulates far above bottom seawater concentrations (~21 μM) throughout the sediment column (up to ~50 μM) down to the oceanic basement as deep as 90mb.s.f. (below sea floor), reflecting the predominance of aerobic nitrification/ remineralization within the deep marine sediments. Large changes in the δ15N and δ18O of nitrate, however, reveal variable influence of nitrate respiration across the three sites. We use an inverse porewater diffusion-reaction model, constrained by the N and O isotope systematics of nitrification and denitrification and the porewater NO3- isotopic composition, to estimate rates of nitrification and denitrification throughout the sediment column. Results indicate variability of reaction rates across and within the three boreholes that are generally consistent with the differential distribution of dissolved oxygen at this site, though not necessarily with the canonical view of how redox thresholds separate nitrate regeneration from dissimilative consumption spatially. That is, we provide stable isotopic evidence for expanded zones of co-occurring nitrification and denitrification. The isotope biogeochemical modeling also yielded estimates for the δ15N and δ18O of newly produced nitrate (δ15NNTR (NTR, referring to nitrification) and δ18ONTR/, as well as the isotope effect for denitrification (15εDNF/ (DNF, referring to denitrification), parameters with high relevance to global ocean models of N cycling. Estimated values of δ15NNTR were generally lower than previously reported δ15N values for sinking particulate organic nitrogen in this region. We suggest that these values may be, in part, related to sedimentary N2 fixation and remineralization of the newly fixed organic N. Values of δ18ONTR generally ranged between -2.8 and 0.0‰, consistent with recent estimates based on lab cultures of nitrifying bacteria. Notably, some δ18ONTR values were elevated, suggesting incorporation of 18O-enriched dissolved oxygen during nitrification, and possibly indicating a tight coupling of NH4+ and NO2- oxidation in this metabolically sluggish environment. Our findings indicate that the production of organic matter by in situ autotrophy (e.g., nitrification, nitrogen fixation) supplies a large fraction of the biomass and organic substrate for heterotrophy in these sediments, supplementing the small organic-matter pool derived from the overlying euphotic zone. This work sheds new light on an active nitrogen cycle operating, despite exceedingly low carbon inputs, in the deep sedimentary biosphere. [ABSTRACT FROM AUTHOR]

Background:Juvenile nasopharyngeal angiofibroma is a benign, vascular tumour that primarily occurs in adolescent males. Despite its benign nature, aggressive growth patterns can cause potential life-threatening complications. Juvenile nasopharyngeal angiofibroma is normally unilateral, originating from the sphenopalatine artery, but bilateral symptoms can occur if a large tumour extends to the contralateral side of the nasopharynx. This paper presents the first reported case of true bilateral extensive juvenile nasopharyngeal angiofibroma involving clinically challenging pre-surgical planning and surgical strategy.Case report:A 21-year-old male presented with increasing bilateral nasal obstruction and discharge. Examination revealed tumours bilaterally and imaging demonstrated non-contiguous tumours. Pre-operative angiography showed strictly ipsilateral vascular supplies requiring bilateral embolisation. Radical removal performed as one-step, computer-assisted functional endoscopic sinus surgery was performed. The follow-up period was uncomplicated.Conclusion:This case illustrates the importance of suspecting bilateral juvenile nasopharyngeal angiofibroma in patients presenting with bilateral symptoms. Our management, including successful pre-operative planning, enabled one-step total removal of both tumours and rapid patient recovery. [ABSTRACT FROM PUBLISHER]

Nitrogen (N) is a key component of fundamental biomolecules. Hence, the cycling and availability of N is a central factor governing the extent of ecosystems across the Earth. In the organic-lean sediment porewaters underlying the oligotrophic ocean, where low levels of microbial activity persist despite limited organic matter delivery from overlying water, the extent and modes of nitrogen transformations have not been widely investigated. Here we use the N and oxygen (O) isotopic composition of porewater nitrate (NO3-) from a site in the oligotrophic North Atlantic (IODP) to determine the extent and magnitude of microbial nitrate production (via nitrification) and consumption (via denitrification). We find that NO3- accumulates far above bottom seawater concentrations (~ 21 µM) throughout the sediment column (up to ~ 50 µM) down to the oceanic basement as deep as 90 mbsf, reflecting the predominance of aerobic nitrification/ remineralization within the deep marine sediments. Large changes in the δ15N and δ18O of nitrate, however, reveal variable influence of nitrate respiration across the three sites. We use an inverse porewater diffusion-reaction model, constrained by the N and O isotope systematics of nitrification and denitrification and the porewater NO3- isotopic composition, to estimate rates of nitrification and denitrification throughout the sediment column. Results indicate variability of reaction rates across and within the three boreholes that are generally consistent with the differential distribution of dissolved oxygen at this site, though not necessarily with the canonical view of how redox thresholds separate nitrate regeneration from dissimilative consumption spatially. That is, we provide isotope evidence for expanded zones of co-ocurring nitrification and denitrification. The isotope biogeochemical modeling also yielded estimates for the δ15N and δ18O of newly produced nitrate (δ15NNTR and δ18ONTR), as well as the isotope effect for denitrification (15"DNF), parameters with high relevance to global ocean models of N cycling. Estimated values of δ15NNTR were generally lower than previously reported δ15N values for sinking PON in this region. We suggest that these values can be related to sedimentary N-fixation and remineralization of the newly fixed organic N. Values of δ18ONTR generally ranged between -2.8 and 0.0 ‰, consistent with recent estimates based on lab cultures of nitrifying bacteria. Notably, some δ18ONTR values were elevated, suggesting incorporation of 18O-enriched dissolved oxygen during nitrification, and possibly indicating a tight coupling of NH4+ and NO2- oxidation in this metabolically sluggish environment. Our findings indicate that the production of organic matter by in situ autotrophy (e.g., nitrification, nitrogen fixation) supply a large fraction of the biomass and organic substrate for heterotrophy in these sediments, supplementing the small organic matter pool derived from the overlying euphotic zone. This work sheds new light on an active nitrogen cycle operating, despite exceedingly low carbon inputs, in the deep sedimentary biosphere. [ABSTRACT FROM AUTHOR]

Background:We assessed the development in the number of new base of tongue squamous-cell carcinoma (BSCC) cases per year in eastern Denmark from 2000 to 2010 and whether HPV may explain any observable increased incidence.Methods:We performed HPV DNA PCR and p16 immunohistochemistry analysis for all (n=210) BSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and the Danish Pathology Data Bank, and genotyped all HPV-positive specimens with amplicon-based next-generation sequencing.Results:The overall crude incidence of BSCCs increased significantly (5.4% per year) during the study period. This was explained by a significant increase in the number of HPV-positive BSCCs (8.1% per year), whereas the number of HPV-negative BSCCs did not increase significantly. The overall HPV prevalence was 51%, with HPV16 as the predominant HPV type.Conclusions:The increased number of HPV-positive BSCCs may explain the increasing incidence of BSCCs in eastern Denmark, 2000-2010. [ABSTRACT FROM AUTHOR]

Objective: Real-time phase-contrast flow MRI at high spatiotemporal resolution was applied to simultaneously evaluate haemodynamic functions in the ascending aorta (AA) and superior vena cava (SVC) during elevated intrathoracic pressure (Valsalva manoeuvre). Methods: Real-time phase-contrast flow MRI at 3T was based on highly undersampled radial gradient-echo acquisitions and phase-sensitive image reconstructions by regularized non-linear inversion. Dynamic alterations of flow parameters were obtained for 19 subjects at 40-ms temporal resolution, 1.33-mm in-plane resolution and 6-mm section thickness. Real-time measurements were performed during normal breathing (10 s), increased intrathoracic pressure (10 s) and recovery (20 s). Results: Real-time measurements were technically successful in all volunteers. During the Valsalva manoeuvre (late strain) and relative to values during normal breathing, the mean peak flow velocity and flow volume decreased significantly in both vessels (p< 0.001) followed by a return to normal parameters within the first 10 s of recovery in the AA. By contrast, flow in the SVC presented with a brief (1-2 heartbeats) but strong overshoot of both the peak velocity and blood volume immediately after pressure release followed by rapid normalization. Conclusion: Real-time phase-contrast flow MRI may assess cardiac haemodynamics non-invasively, in multiple vessels, across the entire luminal area and at high temporal and spatial resolution. Advances in knowledge: Future clinical applications of this technique promise new insights into haemodynamic alterations associated with pre-clinical congestive heart failure or diastolic dysfunction, especially in cases where echocardiography is technically compromised. [ABSTRACT FROM AUTHOR]

Background:A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based on diagnostic measures and definition of p16 overexpression. We evaluated means of p16 and HPV diagnostics, and quantified overexpression of p16 in HPV-positive and -negative OP-SCCs by mode of immunohistochemical staining of carcinoma cells.Methods:PubMed, Embase, and the Cochrane Library were searched from 1980 until October 2012. We applied the following inclusion criteria: a minimum of 20 cases of site-specific OP-SCCs, and HPV and p16 results present. Studies were categorised into three groups based on their definition of p16 overexpression: verbal definition, nuclear and cytoplasmatic staining between 5 and 69%, and 70% staining.Results:We identified 39 studies with available outcome data (n=3926): 22 studies (n=1980) used PCR, 6 studies (n=688) used ISH, and 11 studies (n=1258) used both PCR and ISH for HPV diagnostics. The methods showed similar HPV-positive results. Overall, 52.5% of the cases (n=2062) were HPV positive. As to p16 overexpression, 17 studies (n=1684) used a minimum of 5-69% staining, and 7 studies (n=764) used 70% staining. Fifteen studies (n=1478) referred to a verbal definition. Studies showed high heterogeneity in diagnostics of HPV and definition of p16. The correlation between HPV positivity and p16 overexpression proved best numerically in the group applying 70% staining for p16 overexpression. The group with verbal definitions had a significantly lower false-positive rate, but along with the group applying 5-69% staining showed a worse sensitivity compared with 70% staining.Conclusions:There are substantial differences in how studies diagnose HPV and define p16 overexpression. Numerically, p16 staining is better to predict the presence of HPV (i.e. larger sensitivity), when the cutoff is set at 70% of cytoplasmatic and nuclear staining. [ABSTRACT FROM AUTHOR]

Background:Although the role of human papilloma virus (HPV) in cervical squamous cell carcinoma (CSCC) is well established, the role in head and neck SCC (HNSCC) is less clear. MicroRNAs (miRNAs) have a role in the cancer development, and HPV status may affect the miRNA expression pattern in HNSCC. To explore the influence of HPV in HNSCC, we made a comparative miRNA profile of HPV-positive (HPV+) and HPV-negative (HPV−) HNSCC against CSCC.Methods:Fresh frozen and laser microdissected-paraffin-embedded samples obtained from patients with HPV+/HPV− HNSCC, CSCC and controls were used for microarray analysis. Differentially expressed miRNAs in the HPV+ and HPV− HNSCC samples were compared with the differentially expressed miRNAs in the CSCC samples.Results:Human papilloma virus positive (+) HNSCC had a distinct miRNA profile compared with HPV− HNSCC. Significantly more similarity was seen between HPV+ HNSCC and CSCC than HPV− and CSCC. A set of HPV core miRNAs were identified. Of these especially the miR-15a/miR-16/miR195/miR-497 family, miR-143/miR-145 and the miR-106-363 cluster appear to be important within the known HPV pathogenesis.Conclusion:This study adds new knowledge to the known pathogenic pathways of HPV and substantiates the oncogenic role of HPV in subsets of HNSCCs. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are small non-coding RNAs, which regulate mRNA translation/decay, and may serve as biomarkers. We characterised the expression of miRNAs in clinically sampled oral and pharyngeal squamous cell carcinoma (OSCC and PSCC) and described the influence of human papilloma virus (HPV).Methods: Biopsies obtained from 51 patients with OSCC/PSCC and 40 control patients were used for microarray analysis. The results were correlated to clinical data and HPV status. Supervised learning by support vector machines was employed to generate a diagnostic miRNA signature.Results: One hundred and fourteen miRNAs were differentially expressed between OSCC and normal oral epithelium, with the downregulation of miR-375 and upregulation of miR-31 as the most significant aberrations. Pharyngeal squamous cell carcinoma exhibited 38 differentially expressed miRNAs compared with normal pharyngeal epithelium. Differences in the miRNA expression pattern of both normal epithelium and SCC were observed between the oral cavity compared with the pharynx. Human papilloma virus infection revealed perturbations of 21 miRNAs, most significantly in miR-127-3p and miR363. A molecular classifier including 61 miRNAs was generated for OSCC with an accuracy of 93%.Conclusion: MicroRNAs may serve as useful biomarkers in OSCC and PSCC. The influence of HPV on miRNA may provide a mechanism for the distinct clinical behaviour of HPV-infected tumours. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the treatment outcome for sino-nasal carcinomas in Denmark from 1995-2004 and compare the results to the previous Danish survey covering 1982-1991. Design. Retrospective follow-up. Materials and methods. In the five Danish head and neck oncology centres, charts of all consecutive patients with sino-nasal carcinomas were reviewed and data extracted to a common database. Altogether 242 patients from the period 1995-2004 were identified. Of these 162 (67%) were male and 80 (33%) female. Histologies included squamous cell carcinoma (55%), adenocarcinoma (28.5%), adenoid-cystic carcinoma (5.0%), undifferentiated carcinoma (4.5%), transitiocellular carcinoma (1.7%), mucoepidermoid carcinoma (0.8%), neuroendocrine carcinoma (2.5%), small cell carcinomas (1.2%) and carcinomas not otherwise specified (0.8%). Treatments included radiotherapy alone 79 (33%), surgery alone 29 (12%), combined surgery and radiotherapy 96 (40%), palliative/no treatment 38 (16%). A total of 204 (86%) patients were treated with curative intent. Results. Of the 204 patients treated with curative intent, 94 (46%) relapsed. Most failures were in T-site (63, 30%). N-site failures were 10 (5%) and M-site failures six (3%). Failure occurring in T+N-site, T+M-site, N+M-site and T+N+M-site were seven (3%), two (1%), one (0.5%) and five (3%) respectively. The 5-year actuarial local, nodal and loco-regional control rates were 55±4%, 86±3%, 49±4%, respectively. The overall 5-year actuarial survival rate for the entire cohort was 47±3%, and the corresponding cancer-specific 5-year actuarial survival rate was 57±3%. Female gender, nasal cavity tumour, adenocarcinoma and low clinical stage were significant positive prognostic factors in univariate analysis. A Cox multivariate analysis showed that only tumour site and clinical stage were independent significant prognostic factors. Conclusion. The current series has confirmed stage and tumour site as independent prognostic factors. Compared to the previous Danish survey covering the period 1982-1991, the overall survival and cancer-specific survival rates have improved significantly. [ABSTRACT FROM AUTHOR]

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