Análisis de los tiempos críticos en diagnóstico y tratamiento de Cáncer de Cabeza y Cuello en Complejo Asistencial Sótero del Río / Analysis of critical times in diagnosis and treatment of Head and Neck Cancer at Hospital Sótero del Río

Introducción: El cáncer de cabeza y cuello (CaCyC) representa una alta carga de enfermedad. El retraso del inicio de tratamiento es un factor predictor independiente de mortalidad. Objetivo: Describir los tiempos entre hitos claves diagnósticos y terapéuticos de pacientes con CaCyC atendidos en Hospital Sótero del Río (CASR) y comparar la experiencia local con guías internacionales. Material y Método: Estudio descriptivo-retrospectivo de pacientes presentados en Comité Oncológico de cabeza y cuello (COCYC) del CASR desde septiembre 2020 hasta julio 2022. Se analizan los tiempos críticos del proceso diagnóstico y terapéutico. Resultados: 78 pacientes se seleccionan, 75,5% con carcinoma escamoso. La mediana de tiempos entre derivación desde atención primaria (APS) y evaluación CASR es 2 días, entre evaluación y biopsia es 9 días, y entre diagnóstico histológico e inicio de tratamiento en cualquier modalidad de 27 días. Se comparan los tiempos críticos según los plazos definidos por el Cancer Council Australia. Las tasas de cumplimiento entre derivación APS y evaluación CASR es 67%. Según el tratamiento recibido, la tasa de cumplimiento desde el ingreso al inicio de tratamiento es 70% para cirugía exclusiva, 0% para inicio de radioterapia, y 20% para radioquimioterapia. Para cirugía y radioterapia adyuvante, la tasa es 67% entre evaluación y cirugía, y 6% entre cirugía y radioterapia. Conclusión: Se describen los tiempos entre hitos claves diagnósticos y terapéuticos. Los tiempos de derivación desde APS e inicio de terapias quirúrgicas son comparables a la literatura internacional, pero los tiempos en inicio de radioterapia son mejorables.

Introduction: Head and neck cancer (H&NCa) represents a high burden of disease. Delay in starting treatment is an independent predictor of mortality. Objective: To describe the times between the key diagnostic and therapeutic milestones of patients with H&NCa treated at the Hospital Sótero del Río (CASR) and compare the local experience with international guidelines. Material and Method: descriptive-retrospective study of patients presented to the Head and Neck Oncology Committee (H&NOCO) of the CASR from September 2020 to July 2022. The critical times of the diagnostic and therapeutic process are analyzed. Results: 78 patients are selected, 75.5% with squamous cell carcinoma. The median time between referral from primary care (PC) and CASR evaluation is 2 days, between evaluation and biopsy is 9 days, and between histological diagnosis and initiation of treatment in any modality is 27 days. Critical times are compared according to the deadlines defined by Cancer Council Australia. Compliance rates between PC referral and CASR admission is 67%. Depending on the treatment received, the compliance rate from admission to the start of treatment is 70% for exclusive surgery, 0% for the start of radiotherapy, and 20% for radiochemotherapy. For surgery and adjuvant radiotherapy, the rate is 67% between evaluation and surgery, and 6% between surgery and radiotherapy. Conclusion: Waiting times between key diagnostic and therapeutic process are described. The times of referral from PC and start of surgical therapies are comparable to the international literature. However, times regarding the start radiotherapy can be improved.

Diagnóstico e manejo de carcinoma de células escamosas sinonasal não queratinizante: relato de caso / Diagnosis and management of non-keratinizing sinonasal squamous cell carcinoma: case report

Introdução: o carcinoma de células escamosas (CCE) é uma neoplasia maligna que pode afetar as estruturas sinonasais e se estender para a cavidade oral. Objetivo: relatar o processo de diagnóstico de um CCE sinonasal, o qual cursou com envolvimento oral. Relato do caso: um homem de 61 anos procurou atendimento odontológico com um aumento de volume doloroso em palato duro, rebordo alveolar anterior superior e dorso nasal esquerdo, com a evolução de aproximadamente 2 meses. Sua queixa inicial era congestão nasal. A tomografia computadorizada demonstrou uma lesão ampla e extensa com destruição de cortical vestibular e palatina, além de envolvimento sinonasal. Com a hipótese diagnóstica de neoplasia sinonasal, uma biópsia incisional foi realizada. Resultado: microscopicamente, observou-se células epiteliais neoplásicas que se organizavam em ninhos e cordões invadindo o tecido conjuntivo adjacente que apresentavam individualmente pleomorfismo nuclear e celular, nucléolo evidentes e hipercromasia nuclear. Áreas de necrose central também eram notadas. Com base nas características clínicas, imagenológicas e histopatológicas, o diagnóstico final foi de CCE sinonasal não queratinizante. O tumor foi estadiado pela equipe médica como T3N0M0 (T3 = tamanho do tumor > 2cm com invasão de ossos faciais, sem evidência de metástase nodal N=0 ou à distância M=0). O paciente foi tratado com quimioterapia (Cisplatina e Gencitabina) e 70Gy de radioterapia de indução como terapia inicial e posterior ressecção cirúrgica. Conclusão: a avaliação clínica, imagenológica e exame histopatológico permitiram o diagnóstico eficaz do CCE sinonasal não queratinizante.

Introduction: squamous cell carcinoma (SCC) is a malignant neoplasm that can affect the sinonasal structures and extend to the oral cavity. Objective: to report the process of diagnosis and management of a sinonasal SCC, which had oral involvement. Case report: a 61-year-old man sought dental care with a painful swelling in the hard palate, anterior superior alveolar ridge and left nasal dorsum for a period of approximately 2 months. His initial complaint was nasal congestion. Computed tomography showed a wide and extensive lesion with destruction of the buccal and palatal cortex, in addition to sinonasal involvement. With the diagnostic hypothesis of sinonasal neoplasia, an incisional biopsy was performed. Results: microscopically, neoplastic epithelial cells grouped in nests and cords invading the adjacent connective tissue were observed; individually they presented nuclear and cellular pleomorphism, evident nucleolus and nuclear hyperchromasia. Areas of central necrosis were also noted. Based on the clinical, imaging and histopathological characteristics, the final diagnosis was non- keratinizing sinonasal SCC. The tumor was staged by the medical team as T3N0M0 (T3 = tumor size > 2cm with invasion of facial bones, without evidence of nodal metastasis N=0 or distant metastasis M=0), and the patient was treated with chemotherapy (Cisplatin and Gemcitabine) and 70Gy of induction radiotherapy as initial therapy and subsequent surgical resection. Conclusion: clinical, imaging and histopathological evaluation allowed an effective diagnosis of non- keratinizing sinonasal SCC.

Lesión dermatológica en zona de tatuaje / Dermatological lesion in tattoo area

Los tatuajes representan una situación in vivo única en la que una gran cantidad de sales metálicas y tintes orgánicos permanecen en la piel durante toda la vida. Como resultado de un mayor número de tatuajes realizados, la incidencia de complicaciones cutáneas asociadas a los tatuajes ha aumentado también. En los últimos 30 años se ha evidenciado un aumento de reportes de tumores cutáneos en los tatuajes; sin embargo, muchos autores siguen considerándolo un evento fortuito. Los posibles efectos cancerígenos locales de los tatuajes siguen sin estar claros. Se cree que este efecto podría ser multifactorial y que combina traumatismo de la aguja, inflamación local crónica, factores externos como la exposición a los rayos ultravioleta (UV) y un posible efecto pro-cancerígeno de las tintas. Se necesitan estudios epidemiológicos y clínicos a gran escala para demostrar esta asociación. Se presenta un caso de un hombre de 40 años, conocido sano, quien 2 meses después de tatuarse el hombro derecho, desarrolla una lesión con características clínicas de un queratoacantoma y a quien se le realiza el diagnostico histológico de un carcinoma espinocelular bien diferenciado e invasor.

Tattoos represent a unique in vivo situation where many metallic salts and organic dyes remain on the skin for a lifetime. As a result of a greater number of tattoos performed, the incidence of skin complications associated with tattoos has increased. In addition, in the last 30 years, there has been an increment in reports of skin tumors within tattoos; however, many authors continue to consider it is a coincidental event. The possible local carcinogenic effects of tattoos remain unclear. It is believed that this effect could be multifactorial, combining needle trauma, chronic local inflammation, external factors such as an ultraviolet rays (UV) exposure and a possible pro-cancer effect of the inks. Large-scale epidemiological and clinical studies are needed to demonstrate this association. A case of a known healthy 40-year-old male is presented, in whom 2 months after a tattoo was performed on his right shoulder, he developed a lesion with clinical characteristics of a keratoacanthoma in which the histological diagnosis of a well differentiated and invasive squamous cell carcinoma was made.

Oral basaloid squamous cell carcinoma: A case report with emphasis on histopathological diagnosis criteria.

Basaloid squamous-cell carcinoma (BSCC) is an uncommon variant of squamous cell carcinoma (SCC) consisting of atypical squamous and basaloid cells. It is an aggressive lesion that most commonly affects the oropharynx, being rare in intraoral sites. In this paper, we report the case of a male patient, 42 years old, smoker and chronic drinker, presenting a vegetating and ulcerated leukoerythroplastic lesion, asymptomatic, with five months of evolution, located on the floor of the mouth. Bilateral infarction of the submandibular lymph nodes was observed. Having established the presumptive diagnosis of SCC, an incisional biopsy was performed, which revealed a proliferation of nests and trabeculae of atypical basaloid and squamous cells. Immunohistochemical analysis revealed positivity for AE1/AE3, CK 5, CK 14, p63 and Ki67 (>80%), but negativity for CK7, S-100 and α-SMA. The diagnosis was BSCC. The patient was referred to a head and neck surgery and oncology service for definitive treatment, but died five months after diagnosis. BSCC is a clinicopathological entity whose diagnosis can be challenging. Its aggressive clinical behavior reiterates the relevance of the correct diagnosis for instituting the appropriate treatment. Thus, it is intended, in this work, to discuss the histopathological criteria for differential diagnosis of BSCC, aiming to contribute to its better knowledge and, perhaps, understanding.

Lysyl Oxidase Like-4 (LOXL4) as a tumor marker and prognosticator in advanced stage laryngeal cancer.

INTRODUCTION: Lysyl oxidase-like 4 is an amine oxidase from the lysyl oxidase family that was previously shown to be overexpressed in head and neck cancer and upregulated in response to hypoxia. The possible role of lysyl oxidase-like 4 as a tumor marker in advanced stage larynx cancer was investigated. OBJECTIVE: To investigate the expression of lysyl Oxidase-Like 4 protein in advanced stage laryngeal cancer and elucidate its possible role as a tumor marker, predictor of treatment response and prognosticator. METHODS: Diagnostic specimens of 72 patients treated for stage III-IV laryngeal squamous cell carcinoma were evaluated for lysyl oxidase-like 4 expression by immunohistochemistry. RESULTS: Lysyl oxidase-like 4 expression was correlated with advanced tumor stage (p = 0.041) and better differentiation (p = 0.025) but was independent of tumor diameter (p = 0.456). Response to induction chemotherapy or the need for salvage laryngectomy were not affected by lysyl oxidase-like 4 expression (p = 0.999, p = 0.070 respectively). Increased lysyl oxidase-like 4 expression was associated with better 2 year overall survival in both univariate (p = 0.036) and multivariate analyses (p = 0.014). CONCLUSION: Lysyl oxidase-like 4 expression emerges with advancing stages, is lost with worsening differentiation, and may have tumor suppressive properties in larynx cancer.

Avaliação Clínico-epidemiológica de Pacientes com Carcinoma de Células Escamosas Oral / Epidemiological and Clinical Evaluation of Patients with Oral Squamous Cell Carcinoma / Evaluación Epidemiológica y Clínica de Pacientes con Carcinoma Oral de Células Escamosas

Introdução: O câncer bucal corresponde a cerca de 30% de todos os tumores de cabeça e pescoço. Aproximadamente 90% dessas neoplasias malignas são carcinomas espinocelulares (CEC) e cerca de 15 mil casos novos são estimados a cada ano no Brasil. Objetivo: Avaliar os aspectos clínico-epidemiológicos de pacientes com CEC oral. Método: Estudo observacional, com delineamento transversal, quantitativo e retrospectivo, a partir da análise de prontuários de pacientes com diagnóstico histopatológico de CEC bucal atendidos em um centro de referência em Oncologia da Região Nordeste do Brasil. Variáveis clínicas e epidemiológicas foram coletadas e analisadas. A análise estatística foi realizada utilizando-se o teste de qui-quadrado (p≤0,05). Resultados: Entre os 298 prontuários avaliados, predominaram pacientes do sexo masculino (75,2%), com idade média de 60,4 anos, tabagistas e etilistas (62,0%). A queixa mais frequente foi a presença de ferida ou lesão na boca (61,1%), e o local mais comum foi a língua (62,1%). As variáveis clínicas revelaram estadiamento clínico avançado (III ou IV) em 76,4% dos pacientes. Entre os pacientes com idade até 50 anos, houve maior concentração de homens (p=0,015) e maior consumo de álcool do que entre os pacientes acima dos 50 anos (p=0,010). As demais variáveis não exibiram diferença estatística significante entre os grupos. Conclusão: As características clínico-epidemiológicas relacionadas ao CEC bucal devem ser consideradas para o planejamento de políticas públicas, a fim de prevenir novos casos e permitir a realização de diagnóstico precoce

Introduction: Oral cancer corresponds to about 30% of all head and neck tumors. Approximately 90% of these malignancies are squamous cell carcinomas (SCC) and about 15 thousand new cases are estimated each year in Brazil. Objective: Evaluate the clinical and epidemiological aspects of patients with oral SCC. Method: Observational cross-sectional, quantitative and retrospective design study, based on the analysis of medical records of patients with histopathological diagnosis of oral SCC treated at a reference center in oncology in Brazil's Northeast. Clinical and epidemiological variables were collected and analyzed. Statistical analysis was performed using the chi-square test (p≤0.05). Results: Among the 298 medical records evaluated, male patients predominated (75.2%), with an average age of 60.4 years, smokers and alcoholics (62.0%). The most reported complaint was the presence of a wound or injury in the mouth (61.1%) and the most common location was the tongue (62.1%). Clinical variables revealed advanced clinical staging (III or IV) in 76.4% of patients. Among patients aged up to 50 years, there was high concentration of men (p=0.015) and greater use of alcohol than among patients over 50 years (p=0.010). The other variables did not show a statistically significant difference between the groups. Conclusion: The clinical and epidemiological characteristics related to oral SCC should be considered when planning public policies, in order to prevent new cases as well as to allow for early diagnosis

Introducción: El cáncer oral corresponde a aproximadamente 30% de todos los tumores de cabeza y cuello. Aproximadamente 90% de estos tumores malignos son carcinomas de células escamosas (CCE) y se estiman alrededor de 15 mil casos nuevos cada año en Brasil. Objetivo: Evaluar los aspectos clínicos y epidemiológicos de los pacientes con CCE oral. Método: Estudio observacional, con diseño transversal, cuantitativo y retrospectivo, basado en el análisis de historias clínicas de pacientes con diagnóstico histopatológico de CCE oral tratados en un centro de referencia en Oncología del Noreste de Brasil. Se recogieron y analizaron variables clínicas y epidemiológicas. El análisis estadístico se realizó mediante la prueba de chi-cuadrado (p≤0,05). Resultados: Entre las 298 historias clínicas evaluadas, predominaron los pacientes del sexo masculino (75,2%), con una edad promedio de 60,4 años, fumadores y alcohólicos (62,0%). La queja más frecuente fue la presencia de herida o lesión en la boca (61,1%) y la ubicación más común fue la lengua (62,1%). Las variables clínicas revelaron estadificación clínica avanzada (III o IV) en 76,4% de los pacientes. Entre los pacientes de hasta 50 años, hubo una mayor concentración de hombres (p=0,015) y un mayor consumo de alcohol que entre los pacientes mayores de 50 años (p=0,010). Las otras variables no mostraron una diferencia estadísticamente significativa entre los grupos. Conclusión: Las características clínicas y epidemiológicas relacionadas con el CCE oral deben considerarse al planificar las políticas públicas, a fin de prevenir nuevos casos y permitir un diagnóstico precoz

Carcinoma de células escamosas de la lengua / Squamous cell carcinoma of the tongue

Las neoplasias de la lengua son los tumores más comunes de la cavidad bucal y la mayoría pertenecen a carcinomas de células escamosas. Presentamos dos casos de carcinomas de la lengua, correspondientes a un carcinoma escamoso moderadamente diferenciado y un carcinoma verrugoso, en mujeres de mediana edad con factores de riesgo oncogénicos. Estos tumores pueden tener diversos grados de diferenciación, los cuales determinan su pronóstico y tratamiento.

Tongue neoplasms are the most common in the oral cavity, and the majority correspond to squamous cell carcinomas. We present two cases of tongue carcinomas, corresponding to moderately differentiated squamous cell carcinoma and verrucous carcinoma, in middle-aged women with oncogenic risk factors.These tumors can have various degrees of differentiation, which determine their prognosis and treatment.

Usefulness of protein-based salivary markers in the diagnosis of oral potentially malignant disorders: A systematic review and meta-analysis.

By using a meta-analytical approach, this study aimed to analyse the diagnostic capacity of protein-based biomarkers in saliva for the differential diagnosis of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) from healthy individuals as control group (HCG).Articles on protein-based biomarkers in saliva, which provided quantitative expression in individuals with clinical and histopathological diagnosis of OPMD or oral leukoplakia (OL) were considered eligible. Searches were conducted in eight electronic databases. The methodological quality was assessed using the Quality Assessment of Diagnostic Studies tool (QUADAS-2). Functional analysis was also performed. Meta-analyses were performed using the OpenMeta tool (Analyst).Meta-analysis was possible for 4 of the 11 biomarkers studied. Only the carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA21) were significant for the OSCC/OPMD subgroup, both with a very low heterogeneity. CEA had an OE = 25.854 (CI95%: 13.215-38.492, p< 0.001, I2 = 0) and CYFRA21 had an OE = 9.317 (CI95%: 9.014-9.619, p< 0.001, I2 = 0). For the OPMD/HCG subgroup, only CYFRA21 was significant, with an OE = 3.679 (CI95%: 0.663-6.696, p= 0.017) although with high heterogeneity (I2 = 91.24).The CEA and CYFRA21 markers proved very useful when differentiating OSCC from OPMD. The CYFRA21 was the only protein that was capable of distinguishing between OPMD and healthy controls.

Tinción con azul de toluidina en biopsia dirigida de lesiones displásicas de la mucosa bucal: informe de casos clínicos / Toluidine blue guided biopsy of dysplastic lesions of the oral mucosa: clinical cases report

Objetivo: Los desórdenes de mucosa bucal potencialmente malignos pueden presentar áreas displásicas. En estos casos, la biopsia es un procedimiento imprescindible para un correcto diagnóstico. La inspección visual y la palpación, como método de selección del área de biopsia, ofrecen sensibilidad y especificidad adecuadas pero mejorables. El objetivo de este artículo es presentar una serie de casos clínicos en los que se describen el empleo y la interpretación de la tinción vital con azul de toluidina como método complementario para contribuir a una mejor elección del área de biopsia. Casos clínicos: Se trata de siete casos de lesiones con sospecha de displasia epitelial en mucosa bucal. En cada uno se detalla la correlación de las áreas teñidas con las manifestaciones clínicas y con el diagnóstico de displasia. Además, se muestran patrones de tinción considerados falsos positivos. En la interpretación de la tinción positiva, se tuvieron en cuenta el aspecto superficial y el color de la lesión teñida. El empleo combinado de inspección, palpación y tinción vital podría constituir un procedimiento integral de utilidad para obtener mayor precisión en la determinación del sitio de biopsia en comparación con los mismos procedimientos aplicados de manera individual. En la interpretación de la tinción positiva con azul de toluidina deberían considerarse el aspecto superficial y el color de la lesión teñida (AU)

Aim: Potentially Malignant Disorders in the oral cavity can present dysplastic areas. In these cases, the biopsy is an essential procedure for a correct diagnosis. Visual inspection and palpation, are adequate methods to select the area for the biopsy, however there is margin for improvement. The objective of this article is to present a series of clinical cases in which the use and interpretation of vital staining with Toluidine Blue is described as a complementary method to contribute to a better choice of the biopsy area. Clinical cases: Seven clinical cases that presented lesions with suspected epithelial dysplasia in the oral mucosa were presented. The correlation of the stained areas with the clinical manifestations and with the diagnosis of dysplasia is detailed in each case. Staining patterns considered false positives are also shown. In the interpretation of the positive staining, the superficial appearance and color of the stained lesion were considered. The combined use of inspection, palpation and vital staining could constitute a useful comprehensive procedure to obtain greater precision in determining the biopsy site in relation to the same procedures applied individually. In the interpretation of the positive staining with Toluidine Blue, the superficial appearance and color of the stained lesion should be considered (AU)

SEOM clinical guidelines for the treatment of head and neck cancer (2020).

Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2017 publication, the Spanish Society of Medical Oncology (SEOM) presents an update of the squamous cell HNC diagnosis and treatment guideline. Most relevant diagnostic and therapeutic changes from the last guideline have been updated: introduction of sentinel node biopsy in early oral/oropharyngeal cancer treated with surgery, concomitant radiotherapy with weekly cisplatin 40 mg/m2 in the adjuvant setting, new approaches for HPV-related oropharyngeal cancer and new treatments with immune-checkpoint inhibitors in recurrent/metastatic disease.

Glycolytic pathway candidate markers in the prognosis of oral squamous cell carcinoma: a systematic review with meta-analysis.

Molecular changes that affect mitochondrial glycolysis have been associated with the maintenance of tumor cells. Some metabolic factors have already been described as predictors of disease severity and outcomes. This systematic review was conducted to answer the question: Is the glycolytic pathway correlated with the prognosis of oral squamous cell carcinoma (OSCC)? A search strategy was developed to retrieve studies in English from PubMed, Scopus, and ISI Web of Science using keywords related to squamous cell carcinoma, survival, and glycolytic pathway, with no restriction of publication date. The search retrieved 1273 publications. After the titles and abstracts were analyzed, 27 studies met inclusion criteria. Studies were divided into groups according to two subtopics, glycolytic pathways and diagnosis, which describe the glycolytic profile of OSCC tumors. Several components of tumor energy metabolism found in this review are important predictors of survival of patients with OSCC.

Glycolytic pathway candidate markers in the prognosis of oral squamous cell carcinoma: a systematic review with meta-analysis

Molecular changes that affect mitochondrial glycolysis have been associated with the maintenance of tumor cells. Some metabolic factors have already been described as predictors of disease severity and outcomes. This systematic review was conducted to answer the question: Is the glycolytic pathway correlated with the prognosis of oral squamous cell carcinoma (OSCC)? A search strategy was developed to retrieve studies in English from PubMed, Scopus, and ISI Web of Science using keywords related to squamous cell carcinoma, survival, and glycolytic pathway, with no restriction of publication date. The search retrieved 1273 publications. After the titles and abstracts were analyzed, 27 studies met inclusion criteria. Studies were divided into groups according to two subtopics, glycolytic pathways and diagnosis, which describe the glycolytic profile of OSCC tumors. Several components of tumor energy metabolism found in this review are important predictors of survival of patients with OSCC.

Joint effect of tobacco, alcohol, and oral HPV infection on head and neck cancer risk in the French West Indies.

We investigated the role of tobacco and alcohol consumption on the occurrence of head and neck squamous cell carcinomas (HNSCC), and the joint effects of these factors with oral human papillomavirus (HPV) infection in the French West Indies, in the Caribbean. We conducted a population-based case-control study (145 cases and 405 controls). We used logistic regression models to estimate adjusted odds ratios (OR) and their 95% confidence intervals (CI). Two-way interactions were assessed on both multiplicative and additive scales. Current smoking (OR = 11.6, 95% CI = 6.7-20.1), drinking more than five glasses of alcohol per day (OR = 2.7, 95% CI = 1.2-4.7), and oral infection with High-risk HPV (OR = 2.4, 95% CI = 1.1-5.0) were significantly associated with HNSCC. The combined exposure to tobacco and alcohol produced a significant synergistic effect on the incidence of HNSCC. Oral infection with High-risk HPV increased the risk of HNSCC in never smokers and nondrinkers. The effects of tobacco, alcohol, and of the combined exposure of tobacco and alcohol were substantially lower in HPV-positive than in HPV-negative HNSCC. This is the first case-control study to investigate the role of tobacco smoking, alcohol drinking and oral HPV infection in an Afro-Caribbean population. Although each of these risk factors has a significant effect, our findings indicate that tobacco and alcohol play a less important role in Hr-HPV-positive HNSCC. Further investigations are warranted notably on the interaction of these three risk factors by cancer site.

EBV-negative lymphoepithelial-like carcinoma of the lower lip

Lymphoepithelial-like carcinoma (LEC) is a rare malignant neoplasm, which can be associated with Epstein-Barr virus (EBV) infection. Histologically, LEC is an undifferentiated carcinoma with an intermixed reactive lymphoplasmacytic infiltrate. LEC appears to be an uncommon tumor type of lip carcinoma. An 82-year-old white woman presented a lesion on her lower lip that developed over the last year. The lesion was characterized by ulceration with flat edges, hardened base, painful, and absence of regional lymphadenopathy. Microscopical analysis evidenced an intense inflammatory infiltrate, composed of lymphoplasmacytic cells, associated with scarce pleomorphic epithelial cells. Immunohistochemistry highlighted the LEC cells with strong expression of pan-CK AE1/AE3, EMA, p63, and p53. CD138 was also faintly positive. Ki-67 was >85%. In situ hybridization analysis did not show evidence of EBV. A diagnostic of EBV-negative LEC was made. We present an uncommon type of lip carcinoma, which can represent a diagnostic challenge for clinicians and pathologists.

Descoberta de carcinoma de células escamosas em lesão previamente diagnosticada como líquen plano oral: malignização ou erro de diagnóstico inicial? / Discovery of squamous cell carcinoma in a lesion previously diagnosed as oral lichen planus: malignant trasformation or wrong initial diagnosis? / Descubrimiento de carcinoma espinocelular en lesión previamente diagnosticada como líquen plano oral: malignización o error de diagnóstico inicial

O Líquen Plano Oral (LPO) é uma doença crônica imunologicamente mediada com potencial de malignização incerto. O objetivo desse artigo é relatar um caso de Carcinoma de Células Escamosas (CCE) diagnosticado em paciente com diagnóstico prévio de LPO. Paciente do sexo feminino, 69 anos, foi atendida durante uma campanha de diagnóstico precoce de câncer de boca realizada na cidade de Londrina/PR, sendo detectada uma lesão eritroplásica em língua e encaminhada para uma melhor avaliação. Na anamnese a paciente relatou que há 2 anos atrás foi diagnosticada com LPO através de biópsia em língua, não sendo proposto nenhum tratamento. Ao exame físico, observamos uma mancha eritematosa em borda lateral de língua do lado esquerdo, não apresentando nenhuma outra lesão na cavidade oral. Com a hipótese diagnóstica de eritroplasia, foi requisitada a lâmina da biópsia anterior para análise, que revelou características microscópicas incompatíveis com o diagnóstico de LPO. Optamos então por realizar uma nova biópsia e a análise histopatológica revelou ilhas de células epiteliais malignas invadindo o tecido conjuntivo, estabelecendo o diagnóstico de CCE. A paciente foi encaminhada para tratamento, sendo realizada glossectomia parcial. Em acompanhamento de 6 meses a paciente encontra-se bem e sem sinais de recidiva. A transformação maligna do LPO ainda é discutida na literatura e muitos casos relatados podem se tratar de erro no diagnóstico inicial, como no caso apresentado. O erro de diagnóstico pode levar a morbidades importantes e comprometer o prognóstico do caso(AU)

The Oral Lichen Planus (OLP) is a chronic inflammatory disease with uncertain malignant potential. The main purpose of this article is to report a case of a squamous cell carcinoma (SCC) in a patient with previous diagnosis of OLP. A 69-years-old female patient was examined during an oral cancer prevention campaign in Londrina/PR. At that occasion it was detected an erythroplakia in the tongue and the patient was referred for a better evaluation. The patient reported a previous biopsy and diagnosis of OLP in the tongue 2 years ago, without any treatment. At the physical examination, we observed an erythematous spot on the lateral border of the tongue on the left side, showing no other lesion in the oral cavity. With the diagnostic hypothesis of erythroplakia, the lamina of the previous biopsy was requested for analysis, which revealed microscopic characteristics incompatible with the diagnosis of OLP. We then chose to perform a new biopsy and the histopathological analysis revealed islands of malignant epithelial cells invading the connective tissue, establishing the diagnosis of SCC. The patient was referred for treatment and partial glossectomy was performed. At 6 months follow-up the patient is well and without signs of relapse. The malignant transformation of OLP is still discussed in the literature and many reported cases may be errors in the initial diagnosis, as in the case presented. The diagnostic error can lead to important morbidities and compromise the prognosis of the case(AU)

El Líquen Plano Oral (LPO) es una enfermedad crónica inmunológicamente mediada con potencial de malignización incierta. El objetivo de este artículo es relatar un caso de Carcinoma de Células Escamosas (CCE) diagnosticado en paciente con diagnóstico previo de LPO. El paciente de sexo femenino, de 69 años, fue atendida durante una campaña de diagnóstico precoz de cáncer de boca realizada en la ciudad de Londrina / PR, siendo detectada una lesión eritroplásica en lengua y encaminada para una mejor evaluación. En la anamnesis la paciente relató que hace 2 años fue diagnosticada con LPO a través de biopsia me lengua, no siendo propuesto ningún tratamiento. En el examen físico, observamos una mancha eritematosa en borde lateral de lengua del lado izquierdo, no presentando ninguna otra lesión en la cavidad oral. Con la hipótesis diagnóstica de eritroplasia, se requirió la lámina de la biopsia anterior para análisis, que reveló características microscópicas incompatibles con el diagnóstico de LPO. Optamos entonces por realizar una nueva biopsia y el análisis histopatológico reveló islas de células epiteliales malignas invadiendo el tejido conectivo, estableciendo el diagnóstico de CCE. La paciente fue encaminada para tratamiento, siendo realizada glossectomía parcial. En seguimiento de 6 meses la paciente se encuentra bien y sin signos de recidiva. La transformación maligna del LPO todavía se discute en la literatura y muchos casos reportados pueden tratarse de error en el diagnóstico inicial, como en el caso presentado. El error de diagnóstico puede llevar a morbilidades importantes y comprometer el pronóstico del caso(AU)

Oral lesions detected during a population screening for prevention and early diagnosis of oral cancer and potentially malignant disorders / Lesões orais detectadas durante uma triagem populacional para prevenção e diagnóstico precoce de câncer de boca e lesões potencialmente maligniziveis

Objective: In this paper, we describe the results of an oral cancer prevention campaign for early detecting and diagnosing oral cancer and potentially malignant disorder. Subjects and method: The population screening was performed in one day in which population was recruited by local mass media communication means. Patients with suspicious lesions were referred for final diagnosis with a specialist in oral medicine and pathology. Results: Of 1.282 patients screened, 104 were referred for specialized care and 94 attended for final diagnosis. Of those, only one (1.06%) patient was diagnosed with oral squamous cell carcinoma and 25 (26.5%) with oral potentially malignant disorders, while the diagnosis rates for benign conditions and normality variations were, respectively, 78.7% and 32.9%. Conclusion: These results suggest low awareness regarding oral cancer within this population, flaws in the knowledge regarding oral cancer by dentists, and the need for improvements in the access to the at-risk population for oral cancer.(AU)

Objetivo: neste artigo, descrevemos os resultados de uma campanha de prevenção do câncer de boca para detectar e diagnosticar precocemente câncer de boca e lesões bucais potencialmente maligniziveis. Sujeitos e método: uma triagem populacional foi realizada em um dia em que a população foi recrutada por meios de comunicação de mídia local. Pacientes com lesões suspeitas foram encaminhados para diagnóstico final com especialista em Estomatologia e Patologia Bucal. Resultados: dos 1.282 pacientes selecionados, 104 foram encaminhados para atendimento especializado e 94 atendidos para diagnóstico final. Desses, apenas um (1,06%) paciente foi diagnosticado com carcinoma espinocelular de boca e 25 (26,5%) com lesões bucais potencialmente maligniziveis, enquanto as taxas de diagnóstico para condições benignas e variações de normalidade foram, respectivamente, 78,7% e 32,9%. Conclusão: esses resultados sugerem baixa conscientização sobre o câncer bucal nessa população, falta conhecimento sobre o câncer bucal por dentistas e a necessidade de melhorias no acesso à população em risco de câncer bucal.(AU)

Salivary MicroRNAs for Early Detection of Head and Neck Squamous Cell Carcinoma: A Case-Control Study in the High Altitude Mestizo Ecuadorian Population.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with the highest incidence worldwide. HNSCC is often diagnosed at advanced stages, incurring significant high mortality and morbidity. The use of saliva, as a noninvasive tool for the diagnosis of cancer, has recently increased. Salivary microRNAs (miRNAs) have emerged as a promising molecular tool for early diagnosis of HNSCC. The aim was to identify the differential expression of salivary miRNAs associated with HNSCC in the high altitude mestizo Ecuadorian population. Using PCR Arrays, miR-122-5p, miR-92a-3p, miR-124-3p, miR-205-5p, and miR-146a-5p were found as the most representative ones. Subsequently, miRNAs expression was confirmed in saliva samples from 108 cases and 108 controls. miR-122-5p, miR-92a-3p, miR-124-3p, and miR-146a-5p showed significant statistical difference between cases and controls with areas under the curve (AUC) of 0.73 (p < 0.001), 0.70 (p < 0.001), 0.71 (p = 0.002), and 0.66 (p = 0.008), respectively. miRNAs were also deregulated in between HNSCC localizations. A differentiated expression of miR-122-5p between oral cancer and oropharynx cancer (AUC of 0.96 p = 0.01) was found: miR-124-3p between larynx and pharynx (AUC = 0.97, p < 0.01) and miR-146a-5p between larynx, oropharynx, and oral cavity (AUC = 0.96, p = 0.01). Moreover, miR-122-5p, miR-124-3p, miR-205-5p, and miR-146a-5p could differentiate between HPV+ and HPV- (p=0.004). Finally, the expression profiles of the five miRNAs were evaluated to discriminate HNSCC patient's tumor stages (TNM 2-4). miR-122-5p differentiates TNM 2 and 3 (p = 0.002, AUC = 0.92), miR-124-3p TNM 2, 3, and 4 (p < 0.001, AUC = 98), miR-146a-5p TNM 2 and 3 (p < 0.001, AUC = 0.97), and miR-92a-3p TNM 3 (p < 0.001, AUC = 0.99). Taken together, these findings show that altered expression of miRNAs could be used as biomarkers for HNSCC diagnosis in the high altitude mestizo Ecuadorian population.

Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer.

The human papillomavirus (HPV) is present in a significant fraction of head-and-neck squamous cell cancer (HNSCC). The main goal of this study was to identify distinct co-expression patterns between HPV+ and HPV- HNSCC and to provide insights into potential regulatory mechanisms/effects within the analyzed networks. We selected cases deposited in The Cancer Genome Atlas database comprising data of gene expression, methylation profiles and mutational patterns, in addition to clinical information. The intersection among differentially expressed and differentially methylated genes showed the negative correlations between the levels of methylation and expression, suggesting that these genes have their expression levels regulated by methylation alteration patterns in their promoter. Weighted correlation network analysis was used to identify co-expression modules and a systematic approach was applied to refine them and identify key regulatory elements integrating results from the other omics. Three distinct co-expression modules were associated with HPV status and molecular signatures. Validation using independent studies reporting biological experimental data converged for the most significant genes in all modules. This study provides insights into complex genetic and epigenetic particularities in the development and progression of HNSCC according to HPV status, and contribute to unveiling specific genes/pathways as novel therapeutic targets in HNSCC.

Childhood trauma is predictive for clinical staging, alcohol consumption, and emotional symptoms in patients with head and neck cancer.

BACKGROUND: Traumatic events in childhood have been associated with the occurrence of anxiety and depression in adulthood. This relation has been investigated in patients with breast cancer; however, it has been little explored in patients with other types of cancer. The objective of this study was to evaluate the occurrence of childhood trauma in patients with head and neck cancer and its association with clinicopathological variables and anxiety and depression levels. METHODS: The study included 110 patients with head and neck squamous cell carcinoma (HNSCC) before they started cancer treatment. Clinicopathological and biobehavioral data were collected from patients' medical records. Anxiety and depression levels were assessed with the Beck Anxiety Inventory and the Beck Depression Inventory, respectively. The Childhood Trauma Questionnaire was used to evaluate the occurrence of traumatic events in childhood. RESULTS: One hundred five patients (95.5%) experienced at least 1 type of childhood trauma. Emotional neglect was the most reported childhood trauma (43.8%), and multiple regression revealed that it was an independent variable for advanced clinical staging (ß = 2.15, P = .048) and higher alcohol consumption (ß = 2.32, P = .031). Patients with HNSCC who experienced more traumatic events in childhood had an almost 12 times greater chance of increased depression levels during the pretreatment period (ß = 11.89; P = .0002). The occurrence of physical child neglect was a predictive factor for increased anxiety levels (ß = 4.17, P = 0.029). CONCLUSIONS: Traumatic events in childhood are predictive for advanced clinical staging, alcohol consumption, and emotional symptoms in patients with HNSCC, and they should be considered in clinical and psychological intervention strategies during cancer treatment. Cancer 2018;000:000-000. © 2018 American Cancer Society.

Clinicopathological significance of chemokine receptor (CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4) expression in head and neck squamous cell carcinomas.

BACKGROUND: Head and neck squamous cell carcinoma shows high prevalence of lymph node metastasis at diagnosis, and despite the advances in treatment, the overall 5-year survival is still under 50%. Chemokine receptors have a role in the development and progression of cancer, but their effect in head and neck carcinoma remains poorly characterised. This study aimed to assess the prognostic value of CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4 in head and neck squamous cell carcinomas. METHODS: Immunohistochemical expression of chemokine receptors was evaluated in a retrospective cohort of 76 cases of head and neck squamous cell carcinoma. Clinicopathological associations were analysed using the chi-square test, survival curves were analysed according to the Kaplan-Meier method, and the Cox proportional hazard model was applied for multivariate survival analysis. RESULTS: The chemokine receptors were highly expressed in primary carcinomas, except for CCR1 and CCR3. Significant associations were detected, including the associations between CCR5 expression and lymph node metastasis (N stage, P = .03), advanced clinical stage (P = .003), poor differentiation of tumours (P = .05) and recurrence (P = .01). The high expression of CCR5 was also associated with shortened disease-free survival (HR: 2.85, 95% CI: 1.09-8.14, P = .05), but the association did not withstand the Cox multivariate survival analysis. At univariate analysis, high expression of CCR7 was associated with disease-free survival and low levels of CXCR4 were significantly associated with both disease-specific and disease-free survival. CONCLUSIONS: These findings show that chemokine receptors may have an important role in head and neck squamous cell carcinoma progression, regional lymph node metastasis and recurrence.