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Papers by Antoine Melkane

Research paper thumbnail of Lemierre Syndrome

Pediatric emergency care, May 1, 2010

Lemierre syndrome is a potentially fatal condition after an oropharyngeal infection. It is charac... more Lemierre syndrome is a potentially fatal condition after an oropharyngeal infection. It is characterized by thrombophlebitis of head and neck veins with systemic dissemination of septic emboli. The most frequently isolated pathogen is Fusobacterium necrophorum. We report an unusual case of Lemierre syndrome in a 4-year-old child caused by Staphylococcus aureus, with multivisceral emboli to the brain, orbits, lungs, and heart valves. We also discuss its atypical clinical presentation, the crucial role of imaging in the early diagnosis, and the different treatment modalities of this life-threatening syndrome.

Research paper thumbnail of Sentinel node biopsy in early oral squamous cell carcinomas: Long-term follow-up and nodal failure analysis

Oral Oncology, Jul 1, 2018

Objectives: Evaluate the reliability of sentinel node biopsy (SNB) in T1/T2 cN0 oral squamous cel... more Objectives: Evaluate the reliability of sentinel node biopsy (SNB) in T1/T2 cN0 oral squamous cell carcinoma (OSCC), and compare recurrence-free time (RFT) and overall survival (OS) between patients undergoing SNB and neck dissection (ND). Patients and methods: Patients with T1/T2 cN0 OSCC underwent SNB followed by systematic ND in the first cohort and SNB followed by selective ND in case of positive sentinel nodes (SN) in the second cohort. Results: A total of 229 patients were followed (first cohort 50, second cohort 179). SNs were successfully detected in 93.9% (215/229) of cases. Median follow-up was 5.6 years. Recurrence occurred in 38/215 patients, with isolated nodal recurrence in 18/215 patients. At 5 years, the rate of recurrence-free patients was 80.0% and the rate of patients without isolated nodal recurrence was 90.4%. Negative predictive value of SNB was 92.7%. No statistically significant difference was observed between the two groups regarding RFT and OS. In 83% (10/ 12) of ipsilateral isolated nodal recurrences, primary tumor was located in anterior part of oral cavity. Only 43% (3/7) of SN+ patients with nodal recurrence were eligible for salvage surgery, compared to 91% (10/11) of SNpatients. SNB resulted in fewer complications than ND (8% vs 28%, p < 0.0001). Conclusion: SNB is a reliable staging tool for T1/T2 cN0 OSCC, without adverse effect on patient survival and fewer complications. No late recurrences occurred in long-term follow-up. Close follow-up is mandatory for SN+ patients, who are at higher risk of nodal recurrence and have worse prognosis.

Research paper thumbnail of Barriers to research among residents in Otolaryngology - Head & Neck Surgery around the world

European Annals of Otorhinolaryngology, Head and Neck Diseases, Jun 1, 2019

Objectives: To document the challenges faced by residents in Otolaryngology-Head & Neck Surgery (... more Objectives: To document the challenges faced by residents in Otolaryngology-Head & Neck Surgery (OTL-HNS) around the world to successfully complete research projects. The second objective is to assess if the challenges are uniform worldwide. Methods: A survey was sent to all OTL-HNS under 45 years old from the 2017 IFOS meeting. This survey was conducted by the YO-IFOS group (Young Otolaryngologists of the International Federation of Otolaryngological Societies). Data was collected for a period of 1 month. Demographic characteristics, information regarding research projects conducted and data concerning perceived barriers to completion of research projects were collected. Results: Among the 2787 attendees, 928 responded to the survey (response rate = 33.3%). Of these 928 answers, 267 responses were from residents/interns in OTL-HNS, while 635 responses were from certified otolaryngologists. The three most frequent obstacles to conducting research projects for trainees were limited dedicated time (64%), insufficient financial resources (55%) and lack of education in research (45%). There was no statistical difference in these barriers among the different countries (P > 0.05). Conclusion: This is the first international study that provides insight on trainee's challenges to conduct research projects during residency. Despite the notion that research is essential for generating new knowledge to guide patient care, many residents fail to successfully incorporate research in their surgical curriculum. These obstacles must be addressed by Otolaryngology-Head & Neck Surgery programs in order to facilitate and support resident's research.

Research paper thumbnail of Multifocal adult rhabdomyoma of the head and neck: case report and systematic review of the literature

International Journal of Oral and Maxillofacial Surgery, Mar 1, 2021

La insufi ciencia cardiaca es un síndrome asociado con alta morbilidad y mortalidad, principalmen... more La insufi ciencia cardiaca es un síndrome asociado con alta morbilidad y mortalidad, principalmente debido a episodios de agudización o descompensación. La cardiopatía hipertensiva es una etiología de la insufi ciencia cardiaca con alta prevalencia en el mundo. El hiperaldosteronismo primario es una causa de hipertensión con incidencia creciente, que, independiente de la hipertensión, puede desencadenar miocardiopatía con todas sus consecuencias. En este artículo se presenta el caso de un paciente de cincuenta años con insufi ciencia cardiaca agudizada con disfunción sistólica, asociada a hipertensión resistente y como patología de base un estado con hipersecreción de aldosterona (hiperaldosteronismo primario).

Research paper thumbnail of Republication de : An unusual metastatic submandibular gland tumor

Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Oct 1, 2021

Research paper thumbnail of Unusual Presentation of Merkel Cell Carcinoma

Ear, nose, & throat journal, Apr 11, 2019

Research paper thumbnail of C-CASE 2022: Competence to Excellence01. The Queen Bee phenomenon in Canadian surgical subspecialties: an evaluation of gender biases in the resident training environment02. Barriers to surgical peer coaching — What have we learned, and where do we go from here?03. Shared decision-making and evid...

Canadian Journal of Surgery

S19 01 The Queen Bee phenomenon in Canadian surgical subspecialties: an evaluation of gender bias... more S19 01 The Queen Bee phenomenon in Canadian surgical subspecialties: an evaluation of gender biases in the resident training environment.

Research paper thumbnail of An unusual metastatic submandibular gland tumor

European Annals of Otorhinolaryngology, Head and Neck Diseases, 2021

Research paper thumbnail of Management of oral feeding following total laryngectomy around the world: YO‐IFOS international study

Head & Neck, 2022

BackgroundTo analyze worldwide practices regarding the initiation of oral feeding after total lar... more BackgroundTo analyze worldwide practices regarding the initiation of oral feeding after total laryngectomy (TL).MethodsOnline survey.ResultsAmong the 332 responses received, 278 from 59 countries were analyzed. Our results showed that 45.6% of respondents started water and 45.1% started liquid diet between postoperative days 7 and 10. Semi‐solid feeds were initiated between days 10 and 14 for 44.9% of respondents and a free diet was allowed after day 15 for 60.8% of respondents. This timing was significantly delayed in cases of laryngo‐pharyngectomy and after prior radiotherapy (p < 0.001). A greater proportion of respondents in Africa and Oceania allowed early oral feeding before day 6 as compared with the rest of the world (p < 0.001).ConclusionDespite increasing number of publications, there is still a lack of evidence to support early oral feeding. The majority of respondents preferred to delay its initiation until at least 7 days after surgery.

Research paper thumbnail of Marginal versus Segmental Mandibulectomy in the Treatment of Oral Cavity Cancer: A Systematic Review and Meta-analysis

International Archives of Otorhinolaryngology, Apr 11, 2023

Research paper thumbnail of Human papillomavirus prevalence and clinicopathological associations in oropharyngeal squamous cell carcinoma in the Lebanese population

The Journal of Laryngology & Otology, 2018

ObjectivesTo evaluate for the first time the prevalence of human papillomavirus in oropharyngeal ... more ObjectivesTo evaluate for the first time the prevalence of human papillomavirus in oropharyngeal squamous cell carcinoma in a Middle-Eastern population, and to determine associations between human papillomavirus profiles and clinicopathological characteristics.MethodsA retrospective chart review was conducted of all patients treated for oropharyngeal squamous cell carcinoma at the Hotel Dieu de France University Hospital (Beirut, Lebanon) between January 2010 and 2016. Existing formalin-fixed paraffin-embedded tumour samples were analysed. Human papillomavirus DNA viral load and p16 expression were evaluated using polymerase chain reaction and immunohistochemistry respectively.ResultsThirty patients (mean age of 60 years) were included. Twenty-seven per cent of patients were p16-positive/human papillomavirus DNA positive, 53 per cent were p16-negative/human papillomavirus DNA negative and 20 per cent were p16-positive/human papillomavirus DNA negative. Human papillomavirus 16 was th...

Research paper thumbnail of Lemierre Syndrome

Pediatric emergency care, 2010

Lemierre syndrome is a potentially fatal condition after an oropharyngeal infection. It is charac... more Lemierre syndrome is a potentially fatal condition after an oropharyngeal infection. It is characterized by thrombophlebitis of head and neck veins with systemic dissemination of septic emboli. The most frequently isolated pathogen is Fusobacterium necrophorum. We report an unusual case of Lemierre syndrome in a 4-year-old child caused by Staphylococcus aureus, with multivisceral emboli to the brain, orbits, lungs, and heart valves. We also discuss its atypical clinical presentation, the crucial role of imaging in the early diagnosis, and the different treatment modalities of this life-threatening syndrome.

Research paper thumbnail of MET Genetic Abnormalities Unreliable for Patient Selection for Therapeutic Intervention in Oropharyngeal Squamous Cell

Background: Identification of MET genetic alteration, mutation, or amplification in oropharyngeal... more Background: Identification of MET genetic alteration, mutation, or amplification in oropharyngeal squamous cell carcinoma (OPSCC) could lead to development of MET selective kinase inhibitors. The aim of this study was to assess the frequency and prognostic value of MET gene mutation, amplification, and protein expression in primary OPSCC. Methods: A retrospective chart review was conducted of patients treated for single primary OPSCC between January 2007 and December 2009. Pre-treatment OPSCC tissue samples were analyzed for MET mutations, gene amplification, and overexpression using Sanger sequencing, FISH analysis, and immunohistochemistry respectively. Univariate and multivariate analyses were used to analyze correlations between molecular abnormalities and patient survival. Results: 143 patients were included in this study. Six cases (4%) were identified that had a genetic variation, but previously described mutations such as p.Tyr1235Asp (Y1235D) or p.Tyr1230Cys (Y1230C) were n...

Research paper thumbnail of MET Genetic Abnormalities Unreliable for Patient Selection for Therapeutic Intervention in Oropharyngeal Squamous Cell Carcinoma

PLoS ONE, 2014

Background: Identification of MET genetic alteration, mutation, or amplification in oropharyngeal... more Background: Identification of MET genetic alteration, mutation, or amplification in oropharyngeal squamous cell carcinoma (OPSCC) could lead to development of MET selective kinase inhibitors. The aim of this study was to assess the frequency and prognostic value of MET gene mutation, amplification, and protein expression in primary OPSCC. Methods: A retrospective chart review was conducted of patients treated for single primary OPSCC between January 2007 and December 2009. Pre-treatment OPSCC tissue samples were analyzed for MET mutations, gene amplification, and overexpression using Sanger sequencing, FISH analysis, and immunohistochemistry respectively. Univariate and multivariate analyses were used to analyze correlations between molecular abnormalities and patient survival. Results: 143 patients were included in this study. Six cases (4%) were identified that had a genetic variation, but previously described mutations such as p.Tyr1235Asp (Y1235D) or p.Tyr1230Cys (Y1230C) were not detected. There were 15 high polysomy cases, and only 3 cases met the criteria for true MET amplification, with $10% amplified cells per case. Immunohistochemistry evaluation showed 43% of cases were c-MET negative and in 57% c-MET was observed at the tumor cell level. Multivariate analysis showed no significant association between MET mutation, amplification, or expression and survival. Conclusions: Our study shows a low frequency of MET mutations and amplification in this cohort of OPSCC. There was no significant correlation between MET mutations, amplification, or expression and patient survival. These results suggest that patient selection based on these MET genetic abnormalities may not be a reliable strategy for therapeutic intervention in OPSCC.

Research paper thumbnail of HPV-related oropharyngeal squamous cell carcinomas: A comparison between three diagnostic approaches

American Journal of Otolaryngology, 2014

Purpose: HPV-related oropharyngeal squamous cell carcinomas clearly represent a growing entity in... more Purpose: HPV-related oropharyngeal squamous cell carcinomas clearly represent a growing entity in the head and neck with distinct carcinogenesis, clinico-pathological presentation and survival profile. We aimed to compare the HPV prevalence rates and clinicopathological correlations obtained with three distinct commonly used HPV detection methods. Materials and Methods: p16-immunohistochemistry (IHC), HPV DNA viral load by real-time PCR (qPCR), and HPV genotyping by a reverse hybridization-based line probe assay (INNO-LiPA) were performed on pretreatment formalin-fixed paraffin-embedded tumor samples from 46 patients treated for single primary oropharyngeal carcinomas. Results: Twenty-eight patients (61%) had a p16 overexpression in IHC. Twenty-nine patients (63%) harbored HPV DNA on qPCR. Thirty-four patients (74%) harbored HPV DNA on INNO-LiPA. The concordance analysis revealed a good agreement between both HPV DNA detection methods (κ = 0.65); when both tests were positive, the depicted HPV subtypes were always concordant (HPV16 in 27 cases, HPV18 in 1 case). Agreement was moderate between IHC and qPCR (κ = 0.59) and fair between IHC and INNO-LiPA (κ = 0.22). Conclusions: Certain highly sensitive methods are able to detect the mere presence of HPV without any carcinogenetic involvement while other more specific tests provide proof of viral transcriptional activity and thus evidence of clinically relevant infections. The use of a stepwise approach allows reducing false positives; p16-immunostaining seems to be an excellent screening test and in situ hybridization may overcome some of the PCR limitations.

Research paper thumbnail of Human papillomavirus prevalence and prognostic implication in oropharyngeal squamous cell carcinomas

Head & Neck, 2013

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) is associated with... more Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) is associated with favorable survival. The purpose of this study was to evaluate the prevalence and prognostic significance of the HPV infection through both the p16 expression status and the oncogenic HPV DNA viral load. A retrospective chart review was conducted on all patients treated for oropharyngeal SCC between January 2007 and June 2009. P16 expression status by immunohistochemistry and HPV DNA viral load by quantitative polymerase chain reaction (qPCR) were evaluated on routine pretreatment tumor samples. One hundred thirty-three patients (94 men and 39 women) were included in the study. Mean age was 59 years. One hundred twenty-two lesions (92%) were localized to lymphoid areas. Sixty-seven patients (50%) were p16+, and 87 patients (65%) harbored HPV DNA. The p16+/HPV DNA+ profile (48%) was associated with the most favorable prognosis. HPV16 was responsible for the majority of the infections (89%). HPV is common among oropharyngeal SCC in France, and acts as an independent prognostic factor.

Research paper thumbnail of Épidémiologie Des Cancers Des Voies Aéro-Digestives Supérieures

Research paper thumbnail of Otolaryngologic manifestations of diffuse idiopathic skeletal hyperostosis (Forestier's disease): A systematic review of the literature

Research paper thumbnail of Manifestations ORL de la Maladie de Forestier : Revue Systématique de la Littérature

Research paper thumbnail of International registry of otolaryngologist–head and neck surgeons with COVID‐19

International Forum of Allergy & Rhinology

Research paper thumbnail of Lemierre Syndrome

Pediatric emergency care, May 1, 2010

Lemierre syndrome is a potentially fatal condition after an oropharyngeal infection. It is charac... more Lemierre syndrome is a potentially fatal condition after an oropharyngeal infection. It is characterized by thrombophlebitis of head and neck veins with systemic dissemination of septic emboli. The most frequently isolated pathogen is Fusobacterium necrophorum. We report an unusual case of Lemierre syndrome in a 4-year-old child caused by Staphylococcus aureus, with multivisceral emboli to the brain, orbits, lungs, and heart valves. We also discuss its atypical clinical presentation, the crucial role of imaging in the early diagnosis, and the different treatment modalities of this life-threatening syndrome.

Research paper thumbnail of Sentinel node biopsy in early oral squamous cell carcinomas: Long-term follow-up and nodal failure analysis

Oral Oncology, Jul 1, 2018

Objectives: Evaluate the reliability of sentinel node biopsy (SNB) in T1/T2 cN0 oral squamous cel... more Objectives: Evaluate the reliability of sentinel node biopsy (SNB) in T1/T2 cN0 oral squamous cell carcinoma (OSCC), and compare recurrence-free time (RFT) and overall survival (OS) between patients undergoing SNB and neck dissection (ND). Patients and methods: Patients with T1/T2 cN0 OSCC underwent SNB followed by systematic ND in the first cohort and SNB followed by selective ND in case of positive sentinel nodes (SN) in the second cohort. Results: A total of 229 patients were followed (first cohort 50, second cohort 179). SNs were successfully detected in 93.9% (215/229) of cases. Median follow-up was 5.6 years. Recurrence occurred in 38/215 patients, with isolated nodal recurrence in 18/215 patients. At 5 years, the rate of recurrence-free patients was 80.0% and the rate of patients without isolated nodal recurrence was 90.4%. Negative predictive value of SNB was 92.7%. No statistically significant difference was observed between the two groups regarding RFT and OS. In 83% (10/ 12) of ipsilateral isolated nodal recurrences, primary tumor was located in anterior part of oral cavity. Only 43% (3/7) of SN+ patients with nodal recurrence were eligible for salvage surgery, compared to 91% (10/11) of SNpatients. SNB resulted in fewer complications than ND (8% vs 28%, p < 0.0001). Conclusion: SNB is a reliable staging tool for T1/T2 cN0 OSCC, without adverse effect on patient survival and fewer complications. No late recurrences occurred in long-term follow-up. Close follow-up is mandatory for SN+ patients, who are at higher risk of nodal recurrence and have worse prognosis.

Research paper thumbnail of Barriers to research among residents in Otolaryngology - Head & Neck Surgery around the world

European Annals of Otorhinolaryngology, Head and Neck Diseases, Jun 1, 2019

Objectives: To document the challenges faced by residents in Otolaryngology-Head & Neck Surgery (... more Objectives: To document the challenges faced by residents in Otolaryngology-Head & Neck Surgery (OTL-HNS) around the world to successfully complete research projects. The second objective is to assess if the challenges are uniform worldwide. Methods: A survey was sent to all OTL-HNS under 45 years old from the 2017 IFOS meeting. This survey was conducted by the YO-IFOS group (Young Otolaryngologists of the International Federation of Otolaryngological Societies). Data was collected for a period of 1 month. Demographic characteristics, information regarding research projects conducted and data concerning perceived barriers to completion of research projects were collected. Results: Among the 2787 attendees, 928 responded to the survey (response rate = 33.3%). Of these 928 answers, 267 responses were from residents/interns in OTL-HNS, while 635 responses were from certified otolaryngologists. The three most frequent obstacles to conducting research projects for trainees were limited dedicated time (64%), insufficient financial resources (55%) and lack of education in research (45%). There was no statistical difference in these barriers among the different countries (P > 0.05). Conclusion: This is the first international study that provides insight on trainee's challenges to conduct research projects during residency. Despite the notion that research is essential for generating new knowledge to guide patient care, many residents fail to successfully incorporate research in their surgical curriculum. These obstacles must be addressed by Otolaryngology-Head & Neck Surgery programs in order to facilitate and support resident's research.

Research paper thumbnail of Multifocal adult rhabdomyoma of the head and neck: case report and systematic review of the literature

International Journal of Oral and Maxillofacial Surgery, Mar 1, 2021

La insufi ciencia cardiaca es un síndrome asociado con alta morbilidad y mortalidad, principalmen... more La insufi ciencia cardiaca es un síndrome asociado con alta morbilidad y mortalidad, principalmente debido a episodios de agudización o descompensación. La cardiopatía hipertensiva es una etiología de la insufi ciencia cardiaca con alta prevalencia en el mundo. El hiperaldosteronismo primario es una causa de hipertensión con incidencia creciente, que, independiente de la hipertensión, puede desencadenar miocardiopatía con todas sus consecuencias. En este artículo se presenta el caso de un paciente de cincuenta años con insufi ciencia cardiaca agudizada con disfunción sistólica, asociada a hipertensión resistente y como patología de base un estado con hipersecreción de aldosterona (hiperaldosteronismo primario).

Research paper thumbnail of Republication de : An unusual metastatic submandibular gland tumor

Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Oct 1, 2021

Research paper thumbnail of Unusual Presentation of Merkel Cell Carcinoma

Ear, nose, & throat journal, Apr 11, 2019

Research paper thumbnail of C-CASE 2022: Competence to Excellence01. The Queen Bee phenomenon in Canadian surgical subspecialties: an evaluation of gender biases in the resident training environment02. Barriers to surgical peer coaching — What have we learned, and where do we go from here?03. Shared decision-making and evid...

Canadian Journal of Surgery

S19 01 The Queen Bee phenomenon in Canadian surgical subspecialties: an evaluation of gender bias... more S19 01 The Queen Bee phenomenon in Canadian surgical subspecialties: an evaluation of gender biases in the resident training environment.

Research paper thumbnail of An unusual metastatic submandibular gland tumor

European Annals of Otorhinolaryngology, Head and Neck Diseases, 2021

Research paper thumbnail of Management of oral feeding following total laryngectomy around the world: YO‐IFOS international study

Head & Neck, 2022

BackgroundTo analyze worldwide practices regarding the initiation of oral feeding after total lar... more BackgroundTo analyze worldwide practices regarding the initiation of oral feeding after total laryngectomy (TL).MethodsOnline survey.ResultsAmong the 332 responses received, 278 from 59 countries were analyzed. Our results showed that 45.6% of respondents started water and 45.1% started liquid diet between postoperative days 7 and 10. Semi‐solid feeds were initiated between days 10 and 14 for 44.9% of respondents and a free diet was allowed after day 15 for 60.8% of respondents. This timing was significantly delayed in cases of laryngo‐pharyngectomy and after prior radiotherapy (p < 0.001). A greater proportion of respondents in Africa and Oceania allowed early oral feeding before day 6 as compared with the rest of the world (p < 0.001).ConclusionDespite increasing number of publications, there is still a lack of evidence to support early oral feeding. The majority of respondents preferred to delay its initiation until at least 7 days after surgery.

Research paper thumbnail of Marginal versus Segmental Mandibulectomy in the Treatment of Oral Cavity Cancer: A Systematic Review and Meta-analysis

International Archives of Otorhinolaryngology, Apr 11, 2023

Research paper thumbnail of Human papillomavirus prevalence and clinicopathological associations in oropharyngeal squamous cell carcinoma in the Lebanese population

The Journal of Laryngology & Otology, 2018

ObjectivesTo evaluate for the first time the prevalence of human papillomavirus in oropharyngeal ... more ObjectivesTo evaluate for the first time the prevalence of human papillomavirus in oropharyngeal squamous cell carcinoma in a Middle-Eastern population, and to determine associations between human papillomavirus profiles and clinicopathological characteristics.MethodsA retrospective chart review was conducted of all patients treated for oropharyngeal squamous cell carcinoma at the Hotel Dieu de France University Hospital (Beirut, Lebanon) between January 2010 and 2016. Existing formalin-fixed paraffin-embedded tumour samples were analysed. Human papillomavirus DNA viral load and p16 expression were evaluated using polymerase chain reaction and immunohistochemistry respectively.ResultsThirty patients (mean age of 60 years) were included. Twenty-seven per cent of patients were p16-positive/human papillomavirus DNA positive, 53 per cent were p16-negative/human papillomavirus DNA negative and 20 per cent were p16-positive/human papillomavirus DNA negative. Human papillomavirus 16 was th...

Research paper thumbnail of Lemierre Syndrome

Pediatric emergency care, 2010

Lemierre syndrome is a potentially fatal condition after an oropharyngeal infection. It is charac... more Lemierre syndrome is a potentially fatal condition after an oropharyngeal infection. It is characterized by thrombophlebitis of head and neck veins with systemic dissemination of septic emboli. The most frequently isolated pathogen is Fusobacterium necrophorum. We report an unusual case of Lemierre syndrome in a 4-year-old child caused by Staphylococcus aureus, with multivisceral emboli to the brain, orbits, lungs, and heart valves. We also discuss its atypical clinical presentation, the crucial role of imaging in the early diagnosis, and the different treatment modalities of this life-threatening syndrome.

Research paper thumbnail of MET Genetic Abnormalities Unreliable for Patient Selection for Therapeutic Intervention in Oropharyngeal Squamous Cell

Background: Identification of MET genetic alteration, mutation, or amplification in oropharyngeal... more Background: Identification of MET genetic alteration, mutation, or amplification in oropharyngeal squamous cell carcinoma (OPSCC) could lead to development of MET selective kinase inhibitors. The aim of this study was to assess the frequency and prognostic value of MET gene mutation, amplification, and protein expression in primary OPSCC. Methods: A retrospective chart review was conducted of patients treated for single primary OPSCC between January 2007 and December 2009. Pre-treatment OPSCC tissue samples were analyzed for MET mutations, gene amplification, and overexpression using Sanger sequencing, FISH analysis, and immunohistochemistry respectively. Univariate and multivariate analyses were used to analyze correlations between molecular abnormalities and patient survival. Results: 143 patients were included in this study. Six cases (4%) were identified that had a genetic variation, but previously described mutations such as p.Tyr1235Asp (Y1235D) or p.Tyr1230Cys (Y1230C) were n...

Research paper thumbnail of MET Genetic Abnormalities Unreliable for Patient Selection for Therapeutic Intervention in Oropharyngeal Squamous Cell Carcinoma

PLoS ONE, 2014

Background: Identification of MET genetic alteration, mutation, or amplification in oropharyngeal... more Background: Identification of MET genetic alteration, mutation, or amplification in oropharyngeal squamous cell carcinoma (OPSCC) could lead to development of MET selective kinase inhibitors. The aim of this study was to assess the frequency and prognostic value of MET gene mutation, amplification, and protein expression in primary OPSCC. Methods: A retrospective chart review was conducted of patients treated for single primary OPSCC between January 2007 and December 2009. Pre-treatment OPSCC tissue samples were analyzed for MET mutations, gene amplification, and overexpression using Sanger sequencing, FISH analysis, and immunohistochemistry respectively. Univariate and multivariate analyses were used to analyze correlations between molecular abnormalities and patient survival. Results: 143 patients were included in this study. Six cases (4%) were identified that had a genetic variation, but previously described mutations such as p.Tyr1235Asp (Y1235D) or p.Tyr1230Cys (Y1230C) were not detected. There were 15 high polysomy cases, and only 3 cases met the criteria for true MET amplification, with $10% amplified cells per case. Immunohistochemistry evaluation showed 43% of cases were c-MET negative and in 57% c-MET was observed at the tumor cell level. Multivariate analysis showed no significant association between MET mutation, amplification, or expression and survival. Conclusions: Our study shows a low frequency of MET mutations and amplification in this cohort of OPSCC. There was no significant correlation between MET mutations, amplification, or expression and patient survival. These results suggest that patient selection based on these MET genetic abnormalities may not be a reliable strategy for therapeutic intervention in OPSCC.

Research paper thumbnail of HPV-related oropharyngeal squamous cell carcinomas: A comparison between three diagnostic approaches

American Journal of Otolaryngology, 2014

Purpose: HPV-related oropharyngeal squamous cell carcinomas clearly represent a growing entity in... more Purpose: HPV-related oropharyngeal squamous cell carcinomas clearly represent a growing entity in the head and neck with distinct carcinogenesis, clinico-pathological presentation and survival profile. We aimed to compare the HPV prevalence rates and clinicopathological correlations obtained with three distinct commonly used HPV detection methods. Materials and Methods: p16-immunohistochemistry (IHC), HPV DNA viral load by real-time PCR (qPCR), and HPV genotyping by a reverse hybridization-based line probe assay (INNO-LiPA) were performed on pretreatment formalin-fixed paraffin-embedded tumor samples from 46 patients treated for single primary oropharyngeal carcinomas. Results: Twenty-eight patients (61%) had a p16 overexpression in IHC. Twenty-nine patients (63%) harbored HPV DNA on qPCR. Thirty-four patients (74%) harbored HPV DNA on INNO-LiPA. The concordance analysis revealed a good agreement between both HPV DNA detection methods (κ = 0.65); when both tests were positive, the depicted HPV subtypes were always concordant (HPV16 in 27 cases, HPV18 in 1 case). Agreement was moderate between IHC and qPCR (κ = 0.59) and fair between IHC and INNO-LiPA (κ = 0.22). Conclusions: Certain highly sensitive methods are able to detect the mere presence of HPV without any carcinogenetic involvement while other more specific tests provide proof of viral transcriptional activity and thus evidence of clinically relevant infections. The use of a stepwise approach allows reducing false positives; p16-immunostaining seems to be an excellent screening test and in situ hybridization may overcome some of the PCR limitations.

Research paper thumbnail of Human papillomavirus prevalence and prognostic implication in oropharyngeal squamous cell carcinomas

Head & Neck, 2013

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) is associated with... more Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) is associated with favorable survival. The purpose of this study was to evaluate the prevalence and prognostic significance of the HPV infection through both the p16 expression status and the oncogenic HPV DNA viral load. A retrospective chart review was conducted on all patients treated for oropharyngeal SCC between January 2007 and June 2009. P16 expression status by immunohistochemistry and HPV DNA viral load by quantitative polymerase chain reaction (qPCR) were evaluated on routine pretreatment tumor samples. One hundred thirty-three patients (94 men and 39 women) were included in the study. Mean age was 59 years. One hundred twenty-two lesions (92%) were localized to lymphoid areas. Sixty-seven patients (50%) were p16+, and 87 patients (65%) harbored HPV DNA. The p16+/HPV DNA+ profile (48%) was associated with the most favorable prognosis. HPV16 was responsible for the majority of the infections (89%). HPV is common among oropharyngeal SCC in France, and acts as an independent prognostic factor.

Research paper thumbnail of Épidémiologie Des Cancers Des Voies Aéro-Digestives Supérieures

Research paper thumbnail of Otolaryngologic manifestations of diffuse idiopathic skeletal hyperostosis (Forestier's disease): A systematic review of the literature

Research paper thumbnail of Manifestations ORL de la Maladie de Forestier : Revue Systématique de la Littérature

Research paper thumbnail of International registry of otolaryngologist–head and neck surgeons with COVID‐19

International Forum of Allergy & Rhinology