HPV-relatedness definitions for classifying HPV-related oropharyngeal cancer patient do impact on TNM classification and patients' survival.

BACKGROUND: Given the different nature and better outcomes of oropharyngeal carcinoma (OPC) associated with human papillomavirus (HPV) infection, a novel clinical stage classification for HPV-related OPC has been accepted for the 8th edition AJCC TNM (ICON-S model). However, it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. MATERIAL AND METHODS: The aim of this study was to compare different staging system models proposed for HPV-related OPC patients: 7th edition AJCC TNM, RPA stage with non-anatomic factors (Princess Margaret), RPA with N categories for nasopharyngeal cancer (MD-Anderson) and AHR-new (ICON-S), according to different HPV-relatedness definitions: HPV-DNA detection plus an additional positive marker (p16INK4a or HPV-mRNA), p16INK4a positivity alone or the combination of HPV-DNA/p16INK4a positivity as diagnostic tests. RESULTS: A total of 788 consecutive OPC cases diagnosed from 1991 to 2013 were considered eligible for the analysis. Of these samples, 66 (8.4%) were positive for HPV-DNA and (p16INK4a or HPV-mRNA), 83 (10.5%) were p16INK4a positive and 58 (7.4%) were double positive for HPV-DNA/p16INK4a. ICON-S model was the staging system, which performed better in our series when using at least two biomarkers to define HPV-causality. When the same analysis was performed considering only p16INK4a-positivity, RPA stage with non-anatomic factors (Princess Margaret) has the best classification based on AIC criteria. CONCLUSION: HPV-relatedness definition for classifying HPV-related OPC patient do impact on TNM classification and patients' survival. Further studies assessing HPV-relatedness definitions are warranted to better classify HPV-related OPC patients in the era of de-escalation clinical trials.

Double positivity for HPV-DNA/p16ink4a is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients.

BACKGROUND: The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. METHODS: We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16INK4a/pRb/p53/Cyclin-D1 immunohistochemistry. HPV-DNA positive and a random sample of HPV-DNA negative cases were subjected to HPV-E6*I mRNA detection. Demographic, tobacco/alcohol use, clinical and follow-up data were collected. Multivariate models were used to evaluate factors associated with HPV positivity as defined by four different HPV-relatedness definitions. Proportional-hazards models were used to compare the risk of death and recurrence among HPV-related and non-related OPC. RESULTS: 788 patients yielded a valid HPV-DNA result. The percentage of positive cases was 10.9%, 10.2%, 8.5% and 7.4% for p16INK4a, HPV-DNA, HPV-DNA/HPV-E6*I mRNA, and HPV-DNA/p16INK4a, respectively. Being non-smoker or non-drinker was consistently associated across HPV-relatedness definitions with HPV positivity. A suggestion of survival differences between anatomic sub-sites and treatments was observed. Double positivity for HPV-DNA/p16INK4a showed strongest diagnostic accuracy and prognostic value. CONCLUSIONS: Double positivity for HPV-DNA/p16INK4a, a test that can be easily implemented in the clinical practice, has optimal diagnostic accuracy and prognostic value. Our results have strong clinical implications for patients' classification and handling and also suggest that not all the HPV-related OPC behave similarly.

The Use of HPV16-E5, EGFR, and pEGFR as Prognostic Biomarkers for Oropharyngeal Cancer Patients.

Background: Anti-epidermal-growth-factor-receptor (EGFR) therapies in combination with radiotherapy are being studied on de-escalation clinical trials for HPV-related oropharyngeal cancer (OPC) patients. The HPV16-E5 oncoprotein increases recycling of activated EGFR to the cell surface, enhancing factor signal transduction. Our aim was to evaluate viral HPV16-E5 oncogene expression as well as EGFR and phosphorylated-EGFR (pEGFR), protein levels as biomarkers for clinical outcome in a retrospective cohort of OPC patients. Methods: Formalin-fixed-paraffin-embedded OPCs were collected from 1990 to 2013. OPC samples containing HPV-DNA were subject to viral E6 * I mRNA detection and p16INK4a immunohistochemistry (IHC). HPV16-positive cases were evaluated for HPV16-E5 (RT-PCR) and EGFR/pEGFR (IHC). A stratified and matched random sample of HPV-negative samples was used as control and evaluated for EGFR/pEGFR. Overall survival (OS) and disease free survival (DFS) estimates were assessed for locally advanced OPC patients (stage III, IVa,b 7th edition). Results: Among 788 OPC patient samples, 53 were double positive for HPV16-DNA/p16INK4a. HPV16-E5 expression was found in 41 of 53 samples (77.4%). EGFR expression was observed in 37.7 vs 70.8% of HPV16-positive vs HPV-negative samples, respectively; (adjusted OR = 0.15) 5% CI = 0.04-0.56]). Expression of pEGFR followed an inverse pattern with 39.6 and 24.9% detection in HPV16-positive and HPV-negative samples; (adjusted OR = 1.58 [95% CI = 0.48-5.17]). Within HPV16-positive cases, no association between HPV16-E5/EGFR nor pEGFR was observed. With a median follow-up of 39.36 months (min = 0.03 - max = 272.07), the combination of HPV status and EGFR or pEGFR expression were predictors of better OS (p < 0.001, for both) and DFS (p < 0.001 for EGFR and p = 0.003 for pEGFR). Conclusions: HPV16-E5 is highly expressed on HPV16-positive OPCs. Interestingly, HPV16-positive cases expressed significantly more pEGFR while HPV-negative cases expressed more EGFR. The combinations of HPV status and EGFR or pEGFR may be useful biomarkers for evaluating prognosis outcome in OPC patients.

Amigdalectomía mediante electrodisección y mascarilla laríngea / Electrodissection tonsillectomy with laryngeal mask

Introducción: La electrodisección con bisturí de Colorado® se utiliza desde hace 30 años como alternativa a la disección fría. Alexander fue el primero en publicar resultados de la mascarilla laríngea en otorrinolaringología y cirugía maxilofacial. Posteriormente se ha introducido como alternativa anestésica habitual en nuestra especialidad. Objetivo: El objetivo de este estudio es comprobar los resultados de la aplicación combinada de estas 2 técnicas en amigdalectomías, ya por separado han demostrado sus beneficios. Métodos: Presentamos un estudio observacional prospectivo de 107 amigdalectomías con o sin adenoidectomía pediátricas. Se analizan una serie de variables durante todo el proceso como el dolor (escala de Brodman), la analgesia, el sangrado, el edema de úvula, los días hasta normalizar la dieta, la habituación a la vida normal y los tiempos quirúrgico, anestésico y total de quirófano. Resultados: La técnica de electrodisección con bisturí de Colorado® minimiza el sangrado intraoperatorio y la necesidad de hemostasia. El edema de úvula y el dolor local aumenta comparado con la disección en frío. No hay variaciones clínicas en cuanto a los días que tarda el paciente en recuperar su vida normal. La combinación de la anestesia con mascarilla laríngea y la electrodisección con Colorado® reduce el tiempo quirúrgico, anestésico y total de quirófano. Conclusiones: La combinación de ambas técnicas es un método seguro, rápido y eficaz que se beneficia de las ventajas de ambas sin suponer un aumento de los riesgos quirúrgicos ni anestésicos (AU)

Introduction: The Colorado® microdissection needle has been used for 30 years as an alternative to cold dissection. Alexander was the first to publish the results of laryngeal mask in otorhinolaryngology and maxillofacial surgery. Later on it was introduced as a standard anaesthetic technique in our speciality. Objective: The objective of this study was to compare the results of using laryngeal mask combined with Colorado® microdissection needle in tonsillectomies. The benefits of each of these 2 techniques are already known. Methods: We present a prospective observational study of 107 paediatric tonsillectomies associated or not to adenoidectomy. Variables analysed are pain (Brodman scale), analgesia, bleeding, uvula oedema and days up to the restoration of diet and normal life. Surgical, anaesthetic and total surgery room times are also discussed. Results: The Colorado® electrodissection technique minimised intraoperative bleeding and the need for haemostasis. However, uvula oedema and local pain increased compared with cold dissection. There were no clinical variations in the recovery of normal life. Combining the Colorado® microdissection needle and laryngeal mask reduced intraoperative, anaesthetic and total surgery room times. Conclusions: The combination of these two techniques is a secure, quick and effective method that derives benefits from the advantages of both of them, without increasing surgical or anaesthetic risks (AU)

Electrodissection tonsillectomy with laryngeal mask.

INTRODUCTION: The Colorado® microdissection needle has been used for 30 years as an alternative to cold dissection. Alexander was the first to publish the results of laryngeal mask in otorhinolaryngology and maxillofacial surgery. Later on it was introduced as a standard anaesthetic technique in our speciality. Objective The objective of this study was to compare the results of using laryngeal mask combined with Colorado® microdissection needle in tonsillectomies. The benefits of each of these 2 techniques are already known. Methods We present a prospective observational study of 107 paediatric tonsillectomies associated or not to adenoidectomy. Variables analysed are pain (Brodman scale), analgesia, bleeding, uvula oedema and days up to the restoration of diet and normal life. Surgical, anaesthetic and total surgery room times are also discussed. Results The Colorado® electrodissection technique minimised intraoperative bleeding and the need for haemostasis. However, uvula oedema and local pain increased compared with cold dissection. There were no clinical variations in the recovery of normal life. Combining the Colorado® microdissection needle and laryngeal mask reduced intraoperative, anaesthetic and total surgery room times. Conclusions The combination of these two techniques is a secure, quick and effective method that derives benefits from the advantages of both of them, without increasing surgical or anaesthetic risks.

[Tympanostomy tube placement in children with secretory otitis media: analysis of effects and complications]. / Colocación de tubos de ventilación transtimpánicos en niños con otitis seromucosa: análisis de resultados y complicaciones.

INTRODUCTION AND OBJECTIVES: Tympanostomy tube emplacement is a common surgical procedure in paediatric otolaryngological surgery. This surgery has complications that sometimes depend on the disease and at other times on the treatment. The objective of this study is to know the results obtained with tympanostomy tube emplacement and its complications. MATERIAL AND METHODS: Retrospective study of all the children operated on for tympanostomy tube emplacement over a period of 18 months and with follow-up for at least seven years; this amounted to 143 ears operated on for the first time. The study variables were age, gender, initial appearance of the ear, inner ear contents, type of grommet inserted, duration of grommet and the lack of any hospital monitoring needed after extrusion. RESULTS: One complication or another arose in 46% of the ears. The Donaldson type of grommet with a diameter of 1.27 mm is the one that produced most complications. There were more complications in ears that were worse in the otoscopic examination regardless of the grommet inserted. CONCLUSIONS: The high prevalence of complications and after-effects after grommet emplacement needs long-term follow-up in patients. The results obtained suggest the use of grommets with a smaller internal diameter.

Colocación de tubos de ventilación transtimpánicos en niños con otitis seromucosa: análisis de resultados y complicaciones / Tympanostomy tube emplacement in children with secretory otitis media: analysis of effects and complications

Introducción y objetivos: La colocación de tubos de ventilación transtimpánicos (TVT) es una de las cirugías más habituales de la otorrinolaringología pediátrica. Esta cirugía no está exenta de complicaciones que, a veces, dependen de la propia enfermedad y, otras, de su tratamiento. El objetivo de este estudio es conocer los resultados que hemos obtenido con la colocación de tubos de ventilación transtimpánicos y sus complicaciones. Material y métodos: Estudio retrospectivo de todos los niños intervenidos con colocación de TVT, en un período de 18 meses, y un seguimiento mínimo de 7 años, 143 oídos intervenidos por primera vez. Las variables objeto del estudio son: edad, sexo, aspecto inicial del oído, contenido del oído, tipo de TVT colocado, duración del TVT, complicaciones aparecidas y no necesitar controles hospitalarios tras extrusión del TVT. Resultados: El 46 % de los casos presentaron algún tipo de complicación. El TVT que más complicaciones nos ha producido es el tipo Donaldson de 1,27 mm de diámetro interno. Aparecen más complicaciones en los oídos que estaban peor en la otoscopia independientemente del TVT colocado. Conclusiones: La alta incidencia de complicaciones y/o secuelas tras la colocación de TVT hace necesario el seguimiento de los pacientes durante un largo período. Los resultados obtenidos orientan a utilizar TVT de diámetro interno más pequeño (AU)

Introduction and objectives: Tympanostomy tube emplacement is a common surgical procedure in paediatric otolaryngological surgery. This surgery has complications that sometimes depend on the disease and at other times on the treatment. The objective of this study is to know the results obtained with tympanostomy tube emplacement and its complications. Material and methods: Retrospective study of all the children operated on for tympanostomy tube emplacement over a period of 18 months and with follow-up for at least seven years; this amounted to 143 ears operated on for the first time. The study variables were age, gender, initial appearance of the ear, inner ear contents, type of grommet inserted, duration of grommet and the lack of any hospital monitoring needed after extrusion. Results: One complication or another arose in 46 % of the ears. The Donaldson type of grommet with a diameter of 1.27 mm is the one that produced most complications. There were more complications in ears that were worse in the otoscopic examination regardless of the grommet inserted. Conclusions: The high prevalence of complications and after-effects after grommet emplacement needs long-term follow-up in patients. The results obtained suggest the use of grommets with a smaller internal diameter(AU)