Impact of the COVID-19 Pandemic on Brazilian Head and Neck Surgery Centers

Abstract Objective The outbreak of the COVID-19 pandemic had a considerable impact on the healthcare access, treatment, and follow-up of oncologic patients. The aim of this study was to evaluate how the COVID-19 pandemic has affected consultation and follow-up demand as well as treatment volume at Brazilian Head and Neck Surgery centers. Methods An anonymous online questionnaire was used for collection of data across all Brazilian Head and Neck Surgery Centers across a 3-month period (April‒June 2021). This information included the characteristics of each center, and the perceived self-reported impact of the COVID-19 pandemic on academic activities, residency training, and the diagnosis, treatment, and follow-up of patients with Head and Neck diseases between 2019 and 2020. Results The response rate across the 40 registered Brazilian Head and Neck Surgery Centers was 47.5% (n = 19). The data showed a significant reduction in the total number of consultations (24.8%) and number of attending patients (20.2%) between 2019 and 2020. The total number of diagnostic exams (31.6%) and surgical procedures (13.0%) conducted over this period also decreased significantly. Conclusions The COVID-19 pandemic had a significant national impact on Brazilian Head and Neck Surgery Centers. Future studies should examine the long-term effects of the pandemic on cancer treatment. Level of evidence Evidence from a single descriptive study.

Loss of Caveolin-1 Expression in Tumor Cells is Associated with Increased Aggressiveness and Cell Invasion in Oral Squamous Cell Carcinoma.

BACKGROUND: Changes in Caveolin-1 (CAV-1) expression are related to tumorigenesis. The aim of this study was to evaluate the role of CAV-1 in tumor progression in oral squamous cell carcinoma (SCC) tissue samples and the effect of CAV-1 silencing on two oral tongue SCC (OTSCC) cell lines (SCC-25, from a primary tumor, and HSC-3 from lymph node metastases). METHODS: Mycroarray hybridization, mRNA expression, and immunohistochemistry were performed on OSCC tissue samples and corresponding non-tumoral margin tissues. The effects of CAV-1 silencing (siCAV-1) on cell viability, membrane fluidity, on the expression of epithelial to mesenchymal transition (EMT) markers and on cell migration and invasion capacity of OTSCC cell lines were evaluated. RESULTS: Microarray showed a greater CAV-1 expression (1.77-fold) in OSCC tumors than in non-tumoral tissues and 2.0-fold more in less aggressive OSCCs. However, significant differences in CAV-1 gene expression were not seen between tumors and non-tumoral margins nor CAV-1 with any clinicopathological parameters. CAV-1 protein was localized both in carcinoma and in spindle cells of the tumor microenvironment (TME), and CAV-1 positive TME cells were associated with smaller/more aggressive tumors, independent of the carcinoma cells' expression. Silencing of CAV-1 increased cell viability only in SCC-25 cells. It also stimulated the invasion of HSC-3 cells and increased ECAD and BCAT mRNA in these cells; however, the protein levels of the EMT markers were not affected. CONCLUSION: Decreased expression of CAV-1 by tumor cells in OSCC and an increase in the TME were associated with increased cell invasiveness and tumor aggressiveness.

Impact of the COVID-19 Pandemic on Brazilian Head and Neck Surgery Centers.

OBJECTIVE: The outbreak of the COVID-19 pandemic had a considerable impact on the healthcare access, treatment, and follow-up of oncologic patients. The aim of this study was to evaluate how the COVID-19 pandemic has affected consultation and follow-up demand as well as treatment volume at Brazilian Head and Neck Surgery centers. METHODS: An anonymous online questionnaire was used for collection of data across all Brazilian Head and Neck Surgery Centers across a 3-month period (April‒June 2021). This information included the characteristics of each center, and the perceived self-reported impact of the COVID-19 pandemic on academic activities, residency training, and the diagnosis, treatment, and follow-up of patients with Head and Neck diseases between 2019 and 2020. RESULTS: The response rate across the 40 registered Brazilian Head and Neck Surgery Centers was 47.5% (n=19). The data showed a significant reduction in the total number of consultations (24.8%) and number of attending patients (20.2%) between 2019 and 2020. The total number of diagnostic exams (31.6%) and surgical procedures (13.0%) conducted over this period also decreased significantly. CONCLUSIONS: The COVID-19 pandemic had a significant national impact on Brazilian Head and Neck Surgery Centers. Future studies should examine the long-term effects of the pandemic on cancer treatment. LEVEL OF EVIDENCE: Evidence from a single descriptive study.

Radiofrequency ablation of thyroid nodules: prospective cost-effectiveness analysis in comparison to conventional thyroidectomy.

OBJECTIVE: The objective of this study is to compare the total costs of surgery and radiofrequency (RF) ablation for the treatment of benign thyroid nodules. METHODS: This is a prospective randomized study comparing cases treated with US-guided RF ablation (cases) and surgery (control). They were selected and allocated to groups (thyroidectomy or radioablation) by permuted block randomization in blocks of five cases each. RESULTS: Five cases of RF Ablation were compared with five cases of thyroidectomies conducted in the same period. Similar complication rates were observed in both groups. Shorter operating time and hospital stay were observed for the RF group. In the evaluation of the total cost between procedures, radioblation represented 76% of the cost of partial thyroidectomy. CONCLUSION: This study demonstrated that radioablation has a competitive cost, making it an effective alternative in the treatment of benign thyroid nodules.

Chlorine, chromium, proteins of oxidative stress and DNA repair pathways are related to prognosis in oral cancer.

The comparison of chemical and histopathological data obtained from the analysis of excised tumor fragments oral squamous cell carcinoma (OSCC) with the demographic and clinical evolution data is an effective strategy scarcely explored in OSCC studies. The aim was to analyze OSCC tissues for protein expression of enzymes related to oxidative stress and DNA repair and trace elements as candidates as markers of tumor aggressiveness and prognosis. Tumor fragments from 78 OSCC patients that had undergone ablative surgery were qualitatively analyzed by synchrotron micro-X-ray fluorescence for trace elements. Protein expression of SOD-1, Trx, Ref-1 and OGG1/2 was performed by immunohistochemistry. Sociodemographic, clinical, and histopathological data were obtained from 4-year follow-up records. Disease relapse was highest in patients with the presence of chlorine and chromium and lowest in those with tumors with high OGG1/2 expression. High expression of SOD-1, Trx, and Ref-1 was determinant of the larger tumor. Presence of trace elements can be markers of disease prognosis. High expression of enzymes related to oxidative stress or to DNA repair can be either harmful by stimulating tumor growth or beneficial by diminishing relapse rates. Interference on these players may bring novel strategies for the therapeutic management of OSCC patients.

Transoral endoscopic thyroidectomy vestibular approach: Experience from a multicenter national group with 412 patients.

BACKGROUND: Well-established conventional thyroidectomy has satisfactory outcomes; however, robotic and endoscopic thyroid surgery can avoid visible anterior neck scars. Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is the most recent of these techniques. METHODS: This was a retrospective review of 412 patients who underwent TOETVA from 2017 to 2020 in 13 Brazilian centers. RESULTS: The study included 359 (87.1%) females and 53 (12.9%) males, with a mean age of 40 years. There were 231 (56.1%) total thyroidectomies. The conversion rate was 0.7%. The transient vocal cord palsy rate was 7.6% (30 patients). Temporary and persistent hypocalcemia rates were 4.0% and 0.8%, respectively. There were two cases of infection (0.5%). DISCUSSION: This is a large multi-institute TOETVA study, with one of the largest cohorts published to date that; despite its retrospective nature and selection bias, reached outcomes comparable to previously reported series, this study reinforced safeness, feasibility, and nationwide reproducibility for this technique.

Homeobox gene amplification and methylation in oral squamous cell carcinoma.

OBJECTIVES: Investigate the DNA copy number and the methylation profile of the homeobox genes HOXA5, HOXA7, HOXA9, HOXB5, HOXB13, HOXC12, HOXC13, HOXD10, HOXD11, IRX4 and ZHX1, and correlate them with clinicopathological parameters and overall survival. MATERIAL AND METHODS: DNA from OSCC samples and surgical margins were submitted to DNA amplification by qPCR and to DNA methylation analysis using a DNA Methylation PCR Array System. RESULTS: HOXA5, HOXB5 and HOXD10 were amplified in surgical margins while HOXA9, HOXB13 and IRX4 were amplified in OSCC. HOXD10 demonstrated hypermethylation in half of the tumor while ZHX1 did not show hypermethylation. No correlation of DNA copy number or methylation with clinicopathological parameters or survival was observed. CONCLUSION: HOXA9, HOXB13 and IRX4 genes appears to be regulated by amplification and HOXD10 by methylation in OSCC. Further studies are needed to determine the role of these events in OSCC development.

Transoral endoscopic thyroidectomy vestibular approach: initial experience and comparison with conventional thyroid surgery

Introduction: Recent interest of physicians and patients to prevent scars in the neck in thyroid surgery has fostered the development of several remote access techniques in recent decades. Among the various techniques developed, transoral endoscopic thyroidectomy vestibular approach (TOETVA) has shown to be a safe alternative, in selected cases, to conventional thyroidectomy. Objective: This study aimed to evaluate the results of TOETVA in patients with thyroid nodules and compare them with those in patients undergoing conventional thyroidectomy. Methods: Retrospective cohort study comparing 31 patients submitted to endoscopic versus 30 conventional thyroidectomies, regarding operative time, complications and pain scale. Results: Thirty-one cases of TOETVA were compared with 30 conventional thyroidectomies conducted in the same period in a tertiary care center. Similar complication rates were observed in both groups, with shorter operative time for endoscopic surgery compared with that of traditional access. Conclusion: TOETVA can be safely performed in selected cases, with similar complication rates, and shorter operative time compared with conventional thyroidectomy.

Impact of human papillomavirus status on survival and recurrence in a geographic region with a low prevalence of HPV-related cancer: A retrospective cohort study.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is associated with better tumor-response rates and survival outcomes. However, in some geographic regions, the impact of HPV infection on prognosis remains unclear. The aim of this study was to describe the patterns of recurrence and survival among patients treated for OPSCC in a geographic region with a reported low prevalence of HPV-related OPSCC. METHODS: We retrospectively evaluated 215 patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to IV OPSCC who were treated with upfront surgery or radiation therapy with or without chemotherapy in a tertiary Cancer Center in Brazil. The collected data included demographic information, HPV status, tobacco and alcohol consumption, and pathologic and treatment variables. The patterns of recurrence were recorded according to HPV status. Disease-specific survival and recurrence-free survival were calculated. RESULTS: One hundred twenty-seven (59.1%) patients were diagnosed with HPV-positive OPSCC. According to the AJCC eighth edition, 34 (15.8%), 71 (33%), 47 (21.9%), and 60 (27.9%) patients had stage I, II, III, and IV disease, respectively. Surgery was performed in 109 (50.7%) cases, and upfront chemoradiation regimens were provided in 104 (48.4%, P = .69) patients. Overall, the 5-year cancer-specific survival was 73.5% and 68.1% for patients positive and negative to HPV, respectively. Tobacco status was considered the only independent prognostic factor for survival. Furthermore, HPV status was not associated with differences in recurrence rates (P = .68). While all distant relapses were found to be lung metastases in the HPV-negative group, we observed unusual sites of distant metastases in the HPV-positive group. CONCLUSIONS: HPV status was not associated with higher rates of survival among the investigated population. Moreover, smoking status was considered the only independent prognostic factor for survival. Furthermore, patients with HPV-positive tumors were more likely than patients with HPV-negative OPSCC to have unusual distant metastases.

Análise do padrão de recorrência do carcinoma de células escamosas de orofaringe relacionado ao Papiloma Vírus Humano / Papilloma Virus: related Oropharyngeal squamous cell carcinoma patterns of recurrence analysis

Introdução: O carcinoma de células escamosas (CEC) de orofaringe associado ao Papiloma vírus humano (HPV) está associado a melhores taxas de resposta ao tratamento, além de melhor prognóstico. Entretanto, observamos que em algumas regiões geográficas, onde a prevalência de CEC de orofaringe relacionado ao HPV é menor, o impacto da infecção pelo HPV é pouco estudado pela literatura. Objetivos analisar os padrões de recorrência de carcinomas de células escamosas de orofaringe de acordo com variáveis clinico-patológicas, associação ou não com HPV e tratamento inicial instituído. Método: Foram avaliados retrospectivamente 215 pacientes com diagnóstico de CEC classificados como estádio I a IV (sem metástases à distância) através da classificação da American Joint Committee on Cancer (AJCC), tratados no AC Camargo Cancer Center com intenção curativa por meio de cirurgia inicial ou radioterapia, com ou sem quimioterapia associada. Os dados coletados incluíram informações demográficas, status do HPV, consumo de tabaco e álcool, além de variáveis anatomopatológicas e de tratamento. Os padrões de recorrência foram analisados conforme o status do HPV. A sobrevida livre de doença e a sobrevida livre de recorrência foram calculadas usando curvas de Kaplan-Meier seguindo-se da análise multivariada de Cox. Resultados: Cento e vinte e sete (59,1%) pacientes foram diagnosticados com carcinoma de células escamosas relacionadas ao HPV; a idade média dos pacientes foi de 56 anos. A tonsila foi o sítio mais acometido (n=131) tanto nos pacientes com tumores HPV positivos (n = 78, 59,5%) como HPV negativos (n = 53, 40,5%). De acordo com a oitava edição da AJCC, 34 (15,8%), 71 (33%), 47 (21,9%) e 60 (27,9%) pacientes apresentavam doença em estádio I, II, III e IV, respectivamente. A cirurgia foi inicialmente realizada em 109 (50,7%) casos, e os esquemas de radioterapia concomitante a quimioterapia foram oferecidos como as opções de tratamento inicial para 104 pacientes (48,4%, p = 0,686). No geral, a sobrevida livre de doença em cinco anos foi de 73,5% para pacientes com tumores HPV-positivos e 68,1% para pacientes com tumores HPV-negativos; essa diferença não foi estatisticamente significativa (p = 0,227). O status do tabaco foi considerado o único fator prognóstico independente para a sobrevivência. Além disso, o status do HPV não foi associado a diferenças nas taxas de recorrência (p = 0,680). Observamos também que, enquanto todos os casos de metástases a distância nos pacientes HPV-negativos ocorriam nos pulmões, nos HPV-positivos observamos locais incomuns de doença à distância, como fígado, ossos, pele e sistema nervoso central. Conclusões: O status do HPV esteve associado a maiores taxas de sobrevida na população investigada. No entanto, o tabagismo foi considerado o único fator prognóstico independente para sobrevida livre de doença. Além disso, pacientes com carcinoma de células escamosas de orofaringe relacionados ao HPV apresentaram doença a distância em locais não comumente observados nos pacientes com tumores HPV-negativos

Background: Human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is associated with better tumor-response rates and survival outcomes. However, in some geographic regions with a lower prevalence of HPV-positive OPSCC, the impact of HPV infection on prognosis remains unclear. The aim of this study was to describe the patterns of recurrence and survival among patients treated for OPSCC in a geographic region with a reported low prevalence of HPV-related OPSCC. Methods: We retrospectively evaluated 215 patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to IV (with no distant metastases) OPSCC who were treated with upfront surgery or radiation therapy with or without chemotherapy at AC Camargo Cancer Center, São Paulo, Brazil. The collected data included demographic information, HPV status, tobacco and alcohol consumption, and pathologic and treatment variables. The patterns of recurrence were recorded according to HPV status. Disease-specific survival and recurrence-free survival were calculated using Kaplan-Meier curves and multivariate Cox regression analysis. Results: One hundred twenty-seven (59.1%) patients were diagnosed with HPV-positive OPSCC; the median patient age was 56 years. The tonsils were the most frequent site (131 cases) in both the HPV-positive (n=78, 59.5%) and HPV-negative (n=53, 40.5%) groups. According to the AJCC eighth edition, 34 (15.8%), 71 (33%), 47 (21.9%), and 60 (27.9%) patients had stage I, II, III, and IV disease, respectively. Surgery was initially performed in 109 (50.7%) cases, and upfront chemoradiation regimens were provided as the initial treatment options in 104 (48.4%, p=0.686) patients. Overall, the 5-year cancer- specific survival was 73.5% and 68.1% for HPV-positive and HPV-negative patients, respectively; this difference was not significant (p=0.227). Tobacco status was considered the only independent prognostic factor for survival. Furthermore, HPV status was not associated with differences in recurrence rates (p=0.680). While all distant relapses were found to be lung metastases in the HPV-negative group, we observed unusual sites of distant metastases in the HPV-positive group; five patients presented with liver metastasis, four with bone metastasis, one with skin implants, and one with central nervous system (CNS) disease. Conclusions: HPV status was associated with higher rates of survival among the investigated population. Moreover, smoking status was considered the only independent prognostic factor for survival. Furthermore, patients with HPV-positive tumors were more likely than patients with HPV-negative OPSCC to have unusual sites of distant metastases

Quality of life impairment in patients with head and neck cancer and their caregivers: a comparative study / Comprometimento na qualidade de vida de pacientes com câncer de cabeça e pescoço e de seus cuidadores: estudo comparativo

Abstract Introduction: Head and neck cancer represents 3% of all the types of malignant neoplasms and squamous cell carcinoma (SCC) is responsible for 90% of these cases. There have been some studies evaluating the quality of life of these patients, but little is known about the physical and emotional effects on their caregivers. Objective: To evaluate the quality of life of patients with head and neck cancer and their caregivers by applying validated questionnaires. Methods: Thirty patients with advanced tumors (SCC stage III or IV) and their 30 caregivers were included. Specific questionnaires (Coop/Wonca, EORTC QLQ-C30, EORTC H&N35, Coop/Wonca, and Caregiver Strain Index - CSI) were applied during routine medical consultations. Results: Of the 30 patients, 28 were males and 25 had stage IV tumors, with mean age of 56.6 years. 36.7% had the primary tumor in the oropharynx and 70% reported pain. The functional cognitive, physical, and emotional scales were the most affected. Pain, fatigue, and sleep disorders were the most prevalent symptoms. Of the 30 caregivers, 23 were females and 70% were the primary caregivers. 36.7% of the caregivers had high levels of stress, mainly related to the feeling of incapacity. The comparison between patients and caregivers demonstrated that the two groups had similar quality of life impairment: physical fitness (p = 0.487), mental health (p = 0.615), daily activities (p = 0.793), social activities (p = 0.301), changes in health (p = 0.649), and overall health (p = 0.168). Conclusion: Quality of life impairment is similar between patients and their caregivers. This result demonstrates that not only the patients show quality of life impairment, but their caregivers also have it and at similar proportions.

Resumo Introdução: O câncer de cabeça e pescoço representa 3% de todos os tipos de neoplasias malignas e o carcinoma espinocelular corresponde a 90% dos casos. Há estudos sobre a qualidade de vida desses pacientes, mas pouco se conhece sobre os prejuízos físico e emocional dos seus cuidadores. Objetivo: Avaliar a qualidade de vida de pacientes com câncer de cabeça e pescoço e comparativamente de seus cuidadores a partir da aplicação de questionários validados. Método: A casuística foi constituída de 30 pacientes com tumores avançados (carcinomas espinocelulares de estádio III ou IV) de cabeça e pescoço e 30 cuidadores. Foram aplicados questionários específicos (Coop/Wonca, EORTC QLQ-C30, EORTC H&N35, Coop/Wonca e Caregiver Strain Index - CSI) a partir de visitas de rotina ao ambulatório. Resultados: Dos 30 pacientes, 28 eram do sexo masculino e 25 apresentavam estádio IV, com idade média de 56,6 anos. 36,7% tinham o tumor primário na orofaringe e 70% sentiam dor. As escalas funcionais cognitivas, física e emocional foram as mais afetadas. Dor, fadiga e distúrbio do sono foram os sintomas mais prevalentes. Dos 30 cuidadores, 23 eram do sexo feminino e 70% eram cuidadores primários. 36,7% dos cuidadores apresentaram alto nível de estresse, principalmente relacionado à sensação de incapacidade. A comparação entre pacientes e cuidadores demonstram que os dois grupos apresentam semelhante comprometimento da qualidade de vida: aptidão física (p = 0,487), saúde mental (p = 0,615), atividades diárias (p = 0,793), atividades sociais (p = 0,301), mudança na saúde (p = 0,649), saúde geral (p = 0,168). Conclusão: O comprometimento na qualidade de vida é semelhante entre pacientes e seus cuidadores, ou seja, não só os indivíduos de fato doentes apresentam prejuízo na sua qualidade de vida, mas os seus cuidadores também e na mesma proporção.

Quality of life impairment in patients with head and neck cancer and their caregivers: a comparative study.

INTRODUCTION: Head and neck cancer represents 3% of all the types of malignant neoplasms and squamous cell carcinoma (SCC) is responsible for 90% of these cases. There have been some studies evaluating the quality of life of these patients, but little is known about the physical and emotional effects on their caregivers. OBJECTIVE: To evaluate the quality of life of patients with head and neck cancer and their caregivers by applying validated questionnaires. METHODS: Thirty patients with advanced tumors (SCC stage III or IV) and their 30 caregivers were included. Specific questionnaires (Coop/Wonca, EORTC QLQ-C30, EORTC H&N35, Coop/Wonca, and Caregiver Strain Index - CSI) were applied during routine medical consultations. RESULTS: Of the 30 patients, 28 were males and 25 had stage IV tumors, with mean age of 56.6 years. 36.7% had the primary tumor in the oropharynx and 70% reported pain. The functional cognitive, physical, and emotional scales were the most affected. Pain, fatigue, and sleep disorders were the most prevalent symptoms. Of the 30 caregivers, 23 were females and 70% were the primary caregivers. 36.7% of the caregivers had high levels of stress, mainly related to the feeling of incapacity. The comparison between patients and caregivers demonstrated that the two groups had similar quality of life impairment: physical fitness (p=0.487), mental health (p=0.615), daily activities (p=0.793), social activities (p=0.301), changes in health (p=0.649), and overall health (p=0.168). CONCLUSION: Quality of life impairment is similar between patients and their caregivers. This result demonstrates that not only the patients show quality of life impairment, but their caregivers also have it and at similar proportions.

Produção de voz gástrica em paciente submetido a faringolaringoesofagectomia: Relato de caso / Case Report: total laryngectomy and esophagectomy rehabilitated with gastric speech

Introdução: O câncer de esôfago cervical em estádio avançadopode incluir como conduta terapêutica a remoção cirúrgica dafaringe, laringe e esôfago. A reabilitação vocal teoricamentemais indicada para estes casos seria a Laringe Eletrônica. Noentanto, pode haver outra forma de reabilitação vocal para essespacientes, devido à neuroplasticidade funcional que possibilitaao organismo uma nova adaptação para as funções vocais e/ou fala. Objetivo: Apresentar o caso de um paciente submetidoà faringolaringoesofagectomia total com reconstrução gástricaque desenvolveu voz estomacal como forma de comunicaçãooral. Relato de caso: Participou deste estudo um indivíduodo sexo masculino, raça negra, 43 anos, que foi submetido àpelveglossectomia parcial devido carcinoma espinocelular depelve lingual (T3 N0 M0) em 2007 e faringolaringoesofagectomiapor carcinoma epidermóide no esôfago cervical (T2 N0 M0) comreconstrução com tubo gástrico em 2009. Foi encaminhadopara o serviço de fonoaudiologia sendo reabilitado quanto àcomunicação oral por meio de exercícios para o desenvolvimentoda voz gástrica, adquirida após 2 meses de treinamento.Atualmente o paciente apresenta inteligibilidade e fluência de falaadequadas. Conclusões: Este estudo mostrou que é possívela reabilitação vocal por meio da voz gástrica como alternativade comunicação oral em um paciente submetido às ressecçõesassociadas de esôfago, faringe e laringe.

FGFR4 profile as a prognostic marker in squamous cell carcinoma of the mouth and oropharynx.

BACKGROUND: Fibroblast growth factor receptor 4 (FGFR4) is a member of a receptor tyrosine kinase family of enzymes involved in cell cycle control and proliferation. A common single nucleotide polymorphism (SNP) Gly388Arg variant has been associated with increased tumor cell motility and progression of breast cancer, head and neck cancer and soft tissue sarcomas. The present study evaluated the prognostic significance of FGFR4 in oral and oropharynx carcinomas, finding an association of FGFR4 expression and Gly388Arg genotype with tumor onset and prognosis. PATIENTS AND METHODS: DNA from peripheral blood of 122 patients with oral and oropharyngeal squamous cell carcinomas was used to determine FGFR4 genotype by PCR-RFLP. Protein expression was assessed by immunohistochemistry (IHC) on paraffin-embedded tissue microarrays. RESULTS: Presence of allele Arg388 was associated with lymphatic embolization and with disease related premature death. In addition, FGFR4 low expression was related with lymph node positivity and premature relapse of disease, as well as disease related death. CONCLUSION: Our results propose FGFR4 profile, measured by the Gly388Arg genotype and expression, as a novel marker of prognosis in squamous cell carcinoma of the mouth and oropharynx.