Carcinoma escamocelular bucal. Caso clínico y revisión de la literatura / Oral squamous cell carcinoma. Case report and review of literature

Introducción: el cáncer escamocelular (CEC) representa el 90-95% de todos los tipos de cáncer. En México, la frecuencia de CEC bucal (CECB) se ha incrementado y presenta una incidencia entre el 1 y el 5%. El CECB se asocia con sujetos en la quinta y séptima década de la vida, el sexo masculino, positivos a tabaquismo, alcoholismo, factores genéticos, inmunosupresión, infección por virus del papiloma humano (VPH) y estilos de vida poco saludables, entre otros. El objetivo de este trabajo fue presentar un caso clínico como ejemplo de las características emergentes en un paciente con CECB. Caso clínico: mujer de 38 años, con úlcera indurada, parcialmente adherida a planos profundos y dolorosa, asociada con un aumento de volumen, ubicada en vientre y borde lateral de lengua. Se realizó biopsia y con el diagnóstico histopatológico de carcinoma escamocelular invasor bien diferenciado, se procedió a determinar la presencia delVPH y resultó positivo a VPH 16. Se realizó tratamiento oncológico combinado (quirúrgico-radiación-quimioterapia), con buenos resultados para la paciente respecto a la estética y función. Conclusiones: se analizaron varios estudios que evalúan la presencia del VPH en lesiones de CECB, como un factor de riesgo que involucra con mayor frecuencia casos de pacientes jóvenes, la localización en lengua y antecedentes negativospara tabaquismo y alcoholismo frente a casos de CECB no asociados al VPH. Se requieren datos que contribuyan a dilucidar diversos aspectos aún desconocidos sobre la infección bucal por VPH y su relación con el CECB.

Background: Squamous cell cancer (SCC) represents 90-95% of all types of cancer. In Mexico, the frequency of oral SCC (OSCC) has increased, with an incidence between 1 and 5%. OSCC is associated with subjects in the 5 and 7th decade of life, males, positive for smoking, alcoholism, genetic factors, immunosuppression, human papillomavirus (HPV) infection, and unhealthy lifestyles, among others. Theobjectiveof thisworkwas to presenta clinical case as an example of the emerging characteristics in a patient with OSCC. Clinical case: 38-year-old female patient, with indurated ulcer, partially adhered to deep planes and painful, associated with an increase in volume, located on the belly and lateral edge of the tongue. A biopsy was performed and with the histopathological diagnosis of well differentiated invasive squamous cell carcinoma, the presence of HPV was determined, resulting positive for HPV-16. Combined cancer treatment was performed (surgical radiation-chemotherapy), with good results for the patient regarding aesthetics and function. Conclusions: We analyzed several studies evaluating the presence of HPV in lesions of OSCC, as a risk factor that involves more frequently cases of young patients, with location in tongue, and negative antecedents for smoking and alcoholism compared to cases of OSCC not associated with HPV. Data are required to help elucidate various still unknown aspects of oral HPV infection and its relationship with OSCC.

Supervivencia de cirugía de rescate en carcinoma escamoso de orofaringe / Survival outcomes of salvage surgery in oropharyngeal squamous cell carcinoma

La recurrencia de carcinoma de células escamosas orofaríngeo (CCEOF) se asocia a mal pronóstico, particularmente en recurrencias en etapa avanzada. La cirugía en el contexto de rescate es más complicada por el tratamiento oncológico del tumor primario, por lo tanto, tiene un mayor riesgo de complicaciones y estadía hospitalaria. Sin embargo, la cirugía de rescate es la mejor oportunidad del paciente como tratamiento curativo y para supervivencia a largo plazo. La población de pacientes que reciben tratamiento para CCEOF ha cambiado en la última década, se ha reconocido que la incidencia de virus papiloma humano (VPH) asociado a CCEOF ha generado el gran aumento de CCEOF y el cambio asociado en las características de la población de pacientes, ahora los pacientes son más jóvenes y tienen menos comorbilidades. Con el aumento exponencial en la incidencia de CCEOF, la necesidad de cirugía de rescate en CCEOF podría verse en aumento. En vista del aumento de la incidencia de casos con carcinoma escamoso de orofaringe y su importante relación con el VPH, esta revisión se enfoca en la supervivencia tras cirugía de rescate con intención curativa y evaluar si con los avances en su tratamiento ha mejorado su pronóstico.

Recurrence of oropharyngeal squamous cell carcinoma (OPSCC) is associated with poor prognosis, particularly in advanced stage recurrences. Salvage surgery is complicated by previous oncological treatment of the primary tumor, therefore, it has a higher risk of complications and hospital stay. However, salvage surgery is the patient's best opportunity as a curative treatment and for long-term survival. The population of patients receiving treatment for OPSCC has changed in the last decade, it has been recognized that the incidence of human papilloma virus (HPV) associated OPSCC has generated an increase of OPSCC and changes in the epidemiology of the patient population, with younger patients and with less comorbidities. With the exponential increase in the incidence of OPSCC, the need for salvage surgery in OPSCC could increase in the future. In view of the increase in the incidence of cases with squamous oropharyngeal carcinoma and its relationship with HPV, this review focuses on survival after salvage surgery with curative intent and assessing whether the progress in its treatment has improved its prognosis.

¿Permiten la citología, el genotipado y la anoscopia de alta resolución establecer un protocolo para la detección precoz del carcinoma epidermoide de canal anal en población de riesgo? / Do cytology, genotyping, and high resolution anoscopy allow to establish a protocol for early detection of squamous cell carcinoma of the anal canal in risk population?

Introducción: El cáncer anal ha experimentado un aumento de incidencia en los últimos años. Está mediado por el VPH y precedido de cambios precancerosos planteando la posibilidad de dirigir los esfuerzos preventivos hacia los grupos de alto riesgo. Sigue siendo controvertida la indicación de cribado y los métodos de detección ideales. Objetivo: Validar las pruebas de cribado implementadas en la actualidad comparadas con la biopsia como "gold standard". Material y Métodos: Estudio transversal con recogida de datos prospectiva, en una cohorte de hombres VIH+ que tienen sexo con hombres, pertenecientes al Hospital Gregorio Marañón e Infanta Leonor en un periodo de 2 años. Resultados: Se seleccionaron 179 pacientes con 286 visitas a la consulta de screening en las que se llevaron a cabo 3 pruebas de cribado en paralelo (citología anal, genotipado del VPH y anoscopia de alta resolución (AAR) con toma de biopsia dirigida sobre zona sospechosa o aleatoria). La sensibilidad y especificidad para la detección de displasia de alto grado y cáncer y su grado de concordancia con la biopsia fue la siguiente: citología 3,23%/94,43% (k: 0,03), genotipado de VPH de alto riesgo 90,32%/27,45% (k: 0,05), AAR 32,26%/87,45 (k: 0, 17) siendo el rendimiento diagnóstico de las tres pruebas muy bajo. Conclusión: La citología presenta un rendimiento diagnóstico muy bajo comparado con el genotipado que representa el mayor. A la luz de nuestros resultados, los protocolos clínicos tal y como vienen desarrollándose en la actualidad deberían de ser abandonados.

Introduction: The incidence of anal cancer has increased in recent years. It is mediated by HPV and preceded by precancerous changes, raising the possibility of directing preventive efforts towards high-risk groups. The indication of screening remains controversial and which methods would be the ideal ones. Objective: To validate the screening tests established actually, comparing it with the biopsy considered as the "gold standard". Materials and Methods: A cross-sectional study was performed, with prospective data collection in a cohort of VIH+ patients, who have male homosexual anal relations, belonging to Gregorio Marañón and Infanta Leonor Hospitals in a period of 2 years. Results: A total of 179 patients were selected with 286 visits to the screening Outpatient Clinic in which 3 parallel screening tests were performed (anal cytology, HPV genotyping and high resolution anoscopy (AAR) with a biopsy directed on a suspicious or random area). The sensitivity and specificity for the detection of high-grade dysplasia and cancer and their degree of agreement with the biopsy was as follows: cytology 3.23%/94.43% (k: 0.03), high HPV genotyping. risk 90.32%/27.45% (k: 0.05), AAR 32.26%/87.45 (k: 0, 17), the diagnostic accuracy of the three tests being very low. Conclusion: Cytology shows a very low diagnostic accuracy compared to the genotype that represents the highest one. In light of our results, clinical protocols as they are currently being developed should be abandoned.

High-risk mucosal HPV types associated with squamous cell carcinoma on the nose tip in an immunocompetent young man

Abstract: The oncogenic role of high-risk HPV in anogenital, head and neck, and cervical cancer is well recognized, but not in skin cancer in the general population. Some authors have demonstrated their appearance mainly on the hands and feet, particularly in the area of the nail bed, which could be due to contamination with HPV types from anogenital regions. Here, we describe a case of genital HPV associated with SCC on the nose tip in an immunocompetent young man, which was confirmed by histopathological findings and in situ hybridization. The importance of this report is to highlight the potential role of HPV in the etiology of skin cancer in an immunocompetent individual.

A pilot study on the identification of human papillomavirus genotypes in tongue cancer samples from a single institution in Ecuador

The relationship between human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma has been established. However, data from Ecuador is limited. The objective of this study was to characterize HPV infection in Ecuadorian patients with tongue cancer. Fifty-three patients with tongue cancer treated at the tertiary referral center Sociedad de Lucha Contra el Cancer (SOLCA), Guayaquil, between 2006 and 2011 were identified. Linear Array® HPV genotyping was used to identify the presence and types of HPV on formalin-fixed paraffin-embedded biopsy samples from these patients with tongue cancer. HPV was identified in 42% (n=22) and high-risk (HR) HPV in 17% (n=9), with 18 different HPV types identified. The most common types were the HR HPV 33 (14%) and low-risk HPV 67 (14%), followed by the HR HPV 58. More than one HPV type was identified in 27.3% of cases. HPV 33 was frequently associated with other HPV types. No statistically significant differences in gender (P=0.58) and age (P=0.12) were observed between HPV-positive and HPV-negative cases. HPV was identified in almost half of the tongue cancer samples, with subtypes 33 and 67 being the most common. This suggested that HPV played an important role in this disease in the population studied. Given these results, current HPV vaccines may not be as effective in reducing tongue cancer rates in this population.

Prevalence of HPV and EBV infection andtheir relationship with the p53 and PCNA expression in oral carcinoma patients

Introduction: Infection caused by potentially oncogenic viruses, such as HPV and EBV, favors the role of certain oncoproteins that can induce dysplasias and malignant lesions. Objective: To evaluate the prevalence of HPV and EBV and their relation with the expression of p53 and PCNA in patients with oral carcinoma. Methodology: Twenty-seven oral squamous cell carcinomas (OSCC) were evaluated; DNA extraction was conducted using the QIAamp DNA mini kit; viral detection was obtained using the INNO-LiPA kit for HPV, and nested PCR was used for EBV. The evaluation of molecular markers was performed through immunohistochemical staining. Results: The mean age of the patients was 60.55 +/- 13.94 years, and 52 percent of these were female. Of the patients, 59 percent were tobacco users and 63 percent were alcohol consumers. HPV was detected in 70 percent of the patients with the predominance of genotype 16 (60 percent). As for EBV infection, it was observed in 59 percent of cases. p53 and PCNA immunopositivity corresponded to 44 percent and 59 percent, respectively. The tongue was the anatomical location with highest positivity for both viruses as well as for the expression of molecular markers. The 48 percent of the cases presented infection by both viruses. Conclusion: HPV and EBV infection together with the expression of p53 and PCNA were more frequently observed in advanced stages of the disease, suggesting a more relevant role in the progression than in tumor genesis.

High prevalence of human papillomavirus (HPV) in oral mucosal lesions of patients at the Ambulatory of Oral Diagnosis of the Federal University of Sergipe, Northeastern Brazil

Abstract The role of human papillomavirus (HPV) in oral carcinogenesis is still controversial as detection rates of the virus in oral cavity reported in the literature varies greatly. Objective The aim of this study was to evaluate the frequency of HPV infection and its genotypes in patients with oral lesions at the Ambulatory of Oral Diagnosis of the Federal University of Sergipe, Brazil. Material and Methods We conducted a molecular study with 21 patients (15 females) aged from two to 83 years with clinically detectable oral lesions. Samples were collected through exfoliation of lesions and HPV-DNA was identified using MY09/11 and GP5+/6+ primers. Genotyping was performed by multiplex PCR. Results Benign, premalignant and malignant lesions were diagnosed by histopathology. HPV was detected in 17 samples. Of these, HPV-6 was detected in 10 samples, HPV-18 in four and HPV-16 in one sample. When samples were categorized by lesion types, HPV was detected in two papilloma cases (2/3), five carcinomas (5/6), one hyperplasia (1/1) and nine dysplasia cases (9/11). Conclusion Unlike other studies in the literature, we reported high occurrence of HPV in oral lesions. Further studies are required to enhance the comprehension of natural history of oral lesions.

Prevalencia del virus papiloma humano en pacientes con diagnóstico de carcinoma escamoso de la cavidad oral / Human papilloma virus prevalence in patients diagnosed with squamous carcinoma oral cavity

Aim: To establish the prevalence of HPV in patients with diagnose of Oral Squamous cell carcinoma, treated in the Instituto nacional del Cáncer in fresh tumoral samples. methods: Cross-sectional study. The inclusion criteria were patients over 18 years, histological diagnosis of Oral Squamous cell carcinoma, that haven’t received any previous cancer treatment, in normal physical and mental conditions. All patients signed an informed consent. Samples consisting of fresh biopsies of lesions with clinical and pathological diagnosis were made. The samples were processed in the Programme of Virology, Faculty of Medicine, Universidad de Chile, through PCR and genotyped by Linear Array® (ROCHE). Results: The prevalence of VPH obtained in this patients was of 9.09% (2/22), corresponding 1 to VPH 56. The positive patients for VPH resulted to be a man of 35 years and a woman of 73 years (9%). Conclusion: The prevalence of HPV in this type of patients was 9.09%, similar than the international publications.

Objetivos: Determinar la prevalencia del virus papiloma humano (VPH) en pacientes con diagnóstico de carcinoma escamoso de la cavidad oral (COCE), atendidos en el Instituto nacional del Cáncer (INCANCER). material y método: Estudio de corte transversal. Criterios de inclusión: pacientes mayores de 18 años, con diagnóstico histológico de COCE, que no hubiesen recibido ningún tratamiento oncológico previo, en condiciones físicas y mentales normales. Todos los pacientes firmaron el consentimiento informado. Se les realizó una entrevista y se tomaron muestras que consistieron en biopsias frescas de lesiones con diagnóstico clínico y anatomopatológico de COCE. Las muestras se procesaron en el Programa de Virología de la Facultad de Medicina de la Universidad de Chile, a través de PCR y se genotipificaron mediante Linear Array® (ROCHE). Resultados: La prevalencia de VPH obtenida en estos pacientes fue de un 9,09% (2/22), correspondiendo 1 a VPH 56. Los pacientes positivos para VPH resultaron ser un hombre de 35 años y una mujer de 73 años (9%). Conclusión: La prevalencia del VPH en este tipo de pacientes fue de 9,09%, similar a las publicaciones internacionales.

Análise in situ de proteínas diferencialmente expressas em carcinomas epidermoides penianos por espectrometria de massas utilizando Matrix-Assisted Laser Desorption/Ionization (MALDI) / In situ analysis of protein differentially expressed in penile squamous cell carcinoma by Matrix-Assisted Laser Desorption/Ionization (MALDI) mass spectrometry

O carcinoma de pênis (CaPe) corresponde a uma doença maligna mutilante do homem. É mais frequente em regiões economicamente desprivilegiadas, como o Norte/Nordeste do Brasil, onde frequentemente é diagnosticado como doença mais avançada. Assim, novos marcadores diagnósticos, prognósticos e preditivos de tratamentos terapêuticos ainda são necessários. Abordagens proteômicas, incluindo o MALDI Imaging, podem contribuir neste sentido. Esta técnica emergente de espectrometria de massas permite a visualização da distribuição espacial de centenas de dados moleculares diretamente da superfície de uma secção tecidual, adquiridos por razão massa/carga (m/z). Neste contexto, nosso principal propósito foi integrar dados de proteômica clássica (gel 2D e Cromatografia Líquida acoplada à Espectrometria de Massas) e de MALDI Imaging, para obter padrões diferenciais de proteínas associados com amostras de Carcinoma Epidermoide Peniano usual (relacionado ou não ao HPV) e espécimes normais, a fim de buscar possíveis biomarcadores da doença. Um total de 45 amostras de CaPe, congeladas, foram inicialmente genotipadas para a presença do HPV. Destas, 60% foram positivas para variantes virais de alto risco. A proteômica clássica (N=24) evidenciou níveis diferenciais de 35 proteínas entre amostras de CaPe e controles, e 29 entre CaPe HPV positivo versus negativo (P<0,05; ANOVA). Redes de interações demonstraram que estes perfis proteicos interagiam com clusters de proteínas relacionadas com a carcinogênese e progressão tumoral. Entre eles, se destacaram aqueles formados por proteínas antioxidantes e de adesão celular, presentes em níveis elevados em tumores HPV negativos. A partir dos interactomas, quatro alvos proteicos foram selecionados para a análise in situ por imageamento: Calreticulina, 14-3-3 sigma, Serpina B5 e Glutationa-s-transferase. A aquisição de dados do MALDI Imaging foi conduzida após a digestão in situ pela tripsina, usando uma resolução de 200 µm e faixa de 700-3500 m/z para peptídeos (N=31). Os dados de identificação do gel 2D foram então integrados aos do imageamento. A identidade proteica dos filtros foi confirmada, in silico, por meio da presença de peptídeos teóricos co-localizados com o peptídeo experimental alvo nas secções de CaPe. Não houve associação significativa entre os parâmetros clinicopatológicos e as intensidades de sinal dos alvos (P>0,05, U de Mann-Whitney). Análises não supervisionadas, realizadas a partir dos dados do MALDI Imaging, evidenciaram mapas de segmentação que coindiciram com as regiões tumorais e margens adjacentes livres de neoplasia. Entre os principais valores de m/z diferenciadores estava o pico 1413 ± 2,5 Da, abundante nas regiões tumorais, e correlacionado ao peptídeo experimental m/z 1410,86 referente à proteína Calreticulina (CRT), o. Análises estatísticas (PCA e Curva ROC) indicaram este valor de m/z como potencial biomarcador da doença. Por conseguinte, a CRT foi selecionada para a etapa de validação por imunoistoquímica em tecidos parafinados de CaPe (N=158). Níveis elevados de imunoreatividade da CRT foram associados com piores tempo de sobrevida global (Razão de Risco 2,3; IC-1,46-3,96; P<0,001) e câncer específica (Razão de Risco 4,37; IC-1,66-11,51; P=0,002) nos casos de CaPe. A presença de metástase em linfonodos foi considerado um fator prognóstico independente para o risco de morte pelo câncer (Razão de Risco ­ 14,18; CI-3,29-61,12; P <0,001). A imunoreatividade da CRT também foi capaz de predizer a presença de metástase em linfonodos (Chance de Risco: 1,006; IC- 1,0001-1,0012; p=0,044). Estes dados, em conjunto, sugerem que a CRT pode ser um potencial biomarcador prognóstico do CaPe. A estratégia de integração da proteômica clássica com o MALDI Imaging, mostrou-se uma ferramenta útil na busca de novos biomarcadores para o CaPe. Além disto, o trabalho adicionou uma visão analítica à histopatologia clássica, o que deverá inserir as técnicas utilizadas neste projeto em estudos de Anatomia Patológica, tanto em nossa instituição, quanto no contexto global.

Penile cancer (PeCa) corresponds to a mutilating malignant disease in men. It is more frequent in underprivileged socioeconomic regions (e.g., Noth, North-East of Brazil), where it is frequently diagnosed in advanced stages. Thus, new markers are still needed for early diagnosis, prognosis and prediction of therapy. Proteomic approaches, including MALDI Imaging, could assist in this effort. This emerging spatially resolved mass spectrometric technique can obtain topographical distribution of hundreds of molecules directly from the tissue section surface, mensured by mass/charge ratio (m/z). In this context, our mainly propose was to integrate classic proteomic data (2D gel and Liquid Chromatograph coupled with Mass Spectrometry) with MALDI Imaging to obtain diferential patterns of protein associated with Usual Squamous Cell Penile Carcinoma (HPV related or not) and normal specimens, to look for possible biomarkers of the disease. A total of 45 fresh-frozen PeCa samples were initially searched for HPV genotype, 60% of which were positive for high-risk HPV. Classic proteomics (N=24) demonstrated diferential levels of 35 proteins comparing PeCa and control samples, and 29 comparing HPV-positive versus HPV-negative PeCa samples (P<0.05; ANOVA). Protein networks showed that these protein profiles interact with clusters of proteins related with tumorigenesis and tumor progression processes. Among them, antioxidant and cell adhesion proteins play a critical role in HPV negative penile tumors. Based on interactome data, four protein targets were selected for in situ analyses by imaging: Calreticulin, 14-3-3 protein sigma, Serpin B5 and Glutatione-s-transferase. MALDI Imaging data acquisition of peptides was conducted after in situ trypsin digestion using a lateral resolution of 200 µm, covering the range 700- 3500 m/z (N=31). After that, 2D gel based proteomic data was integrated with Imaging data. The filter protein identities were confirmed in silico by the co-localization of theoretical triptic peptides with the experimental peptides in PeCa sections. There was no significant association between the clinical and pathological parameters and the target signal intensities (P>0.05; U de Mann-Whitney). An unsupervised clustering analysis based on MALDI Imaging data reveled segmentation maps that coincide with histological annotation for tumor and adjacent non-neoplasic regions. Among the mainly differentiating m/z values there was 1413 ± 2.5 Da. This peak was especially co-localized with tumoral regions and correlated with Calreticulin (CRT) experimental peptide (m/z 1410,86). Statistical analysis (PCA and ROC Curves) indicated this m/z value as a potencial biomarker of the disease. For this reason, CRT was selected for validation by immunohistochemistry performed on paraffin-embedded PeCa tissues (N=158). As result, CRT hiperexpression in PeCa tissue increased the risk of unfavorable overall survival (Relative Risk ­ 2.3; CI-1.46-3.96; P<0.001) and cancer specific survival (Relative Risk ­ 4.37; CI-1.66-11.51; P=0.002) in these patients. Lymph node metastasis represented an independent prognostic risk factor for death related to cancer in our patients (Relative risk ­ 14.18; CI-3.29-61.12; P <0.001). CRT immunoreactivity was also capable to predict the presence of lymph node metastases (Risk Chance ­ 1,006; CI-1.0001-1.00123; P =0.044). Taken together, our results sugest that CRT may represent a prognostic biomarker of PeCa. The strategy of integrated classic proteomic and MALDI Imaging revealed as usefull tool to search for news biomarkers of the disease. Futhermore, this work added an analytical perspective to the classical histopathology, allowing to include the techniques used in this project in future morphological studies, both in our institution and in the global context.

Prevalence of oral and oropharyngeal human papillomavirus infection in Brazilian population studies: a systematic review / Prevalência de infecção oral e orofaríngea pelo HPV em estudos na população brasileira: revisão sistemática

ABSTRACT INTRODUCTION: Human papillomavirus has been associated with head and neck squamous cell carcinoma. However, there is no conclusive evidence on the prevalence of oral or pharyngeal infection by human papillomavirus in the Brazilian population. OBJECTIVE: To determine the rate of human papillomavirus infection in the Brazilian population. METHODS: Systematic review of published articles. Medline, The Cochrane Library, Embase, Lilacs (Latin American and Caribbean Health Sciences) and Scielo electronic databases were searched. The search included published articles up to December 2014 in Portuguese, Spanish and English. A wide search strategy was employed in order to avoid publication biases and to assess studies dealing only with oral and/or oropharyngeal human papillomavirus infections in the Brazilian population. RESULTS: The 42 selected articles enrolled 4066 patients. It was observed that oral or oropharyngeal human papillomavirus infections were identified in 738 patients (18.2%; IC 95 17.6-18.8), varying between 0.0% and 91.9%. The prevalences of oral or oropharyngeal human papillomavirus infections were respectively 6.2%, 44.6%, 44.4%, 27.4%, 38.5% and 11.9% for healthy people, those with benign oral lesions, pre-malignant lesions, oral or oropharyngeal squamous cell carcinoma, risk groups (patients with genital human papillomavirus lesions or infected partners) and immunocompromised patients. The risk of human papillomavirus infection was estimated for each subgroup and it was evident that, when compared to the healthy population, the risk of human papillomavirus infection was approximately 1.5-9.0 times higher, especially in patients with an immunodeficiency, oral lesions and squamous cell carcinoma. The rates of the most well-known oncogenic types (human papillomavirus 16 and/or 18) also show this increased risk. CONCLUSIONS: Globally, the Brazilian healthy population has a very low oral human papillomavirus infection rate. Other groups, such as at-risk patients or their partners, immunocompromised patients, people with oral lesions and patients with oral cavity or oropharyngeal squamous cell carcinoma have a high risk of human papillomavirus infection.

RESUMO Introdução: O papilomavírus humano (HPV) tem sido associado ao carcinoma de células escamosas (CCE) de cabeça e pescoço. No entanto, não existem evidências conclusivas sobre a prevalência de infecção oral ou faríngea pelo HPV na população brasileira. Objetivo: Determinar a taxa de infecção pelo HPV na população brasileira. Método: Revisão sistemática de artigos publicados. Foram feitas buscas nos seguintes bancos de dados eletrônicos: Medline, The Cochrane Library, Embase, Lilacs (Latin American and Caribbean Health Sciences) e Scielo. A busca considerou artigos publicados até dezembro de 2014, em português, espanhol e inglês. Foi utilizada uma ampla estratégia de busca com o intuito de evitar viés de publicação e também para que fossem avaliados estudos que tratassem apenas de infecções orais e/ou orofaríngeas pelo HPV na população brasileira. Resultados: Os 42 artigos selecionados incluíram 4.066 pacientes. Observou-se que infecções orais ou orofaríngeas pelo HPV foram identificadas em 738 pacientes (18,2%; IC95 17,6-18,8), variando entre 0,0-91,9%. As prevalências de infecções orais ou orofaríngeas pelo HPV foram, respectivamente, 6,2%, 44,6%, 44,4%, 27,4%, 38,5% e 11,9% em pacientes saudáveis, com lesões orais benignas, com lesões pré-malignas, com CCE oral ou orofaríngeo, grupos de risco (pacientes com lesões genitais pelo HPV ou parceiros infectados) e pacientes imunodeficientes. O risco de infecção pelo HPV foi estimado para cada subgrupo, quando ficou evidente que, em comparação com a população saudável, o risco de infecção por HPV foi aproximadamente 1,5-9,0 vezes mais alto, especialmente em pacientes com imunodeficiência, lesões orais e CCE. Os percentuais dos tipos oncogênicos mais conhecidos (HPV 16 e/ou 18) também mostram esse aumento no risco. Conclusões: A população brasileira saudável apresenta taxa de infecção oral pelo HPV muito baixa. Outros grupos, por exemplo, pacientes de risco ou seus parceiros, pacientes imunodeficientes, indivíduos portadores de lesões orais e pacientes com CCE de cavidade oral ou orofaringe apresentam maior risco de infecção pelo HPV.

Proteomics analysis of tissue samples from patients with squamous cell carcinoma of the penis and positive to human papillomavirus

ABSTRACTPurpose:The aim of this study was to identify possible protein biomarkers and/or candidates for therapeutic targets in tissues of patients with SCCP, infected by HPV, applying one dimensional electrophoresis (1DE), followed by direct mass spectrometry (MS) analysis.Materials and Methods:Tissues from 10 HPV positive patients with SCCP and from 10 patients with HPV negative non-tumorous penile foreskins were analyzed applying 1D electrophoresis, followed by analysis with direct mass spectrometry (MS).Results:Sixty-three different proteins were identified in the first group and 50 in the second group. Recognition was possible for 28 proteins exclusively detected in Group 1 and 21 proteins presented only in Group 2.Conclusion:Some proteins in the first group are directly involved in the development of other types of cancer, and therefore, suitable for analysis. Complement C3 protein is a strong candidate for evaluating SCCP patients.

Detección temprana de la displasia anal con citología (PAP) y anoscopía de alta resolución (AAR) en la población de riesgo: experiencia inicial / Early detection of anal dysplasia with cytology (PAP) and high resolution anoscopy (AAR) in the population at risk: initial experience

Antecedentes: La incidencia del carcinoma de células escamosas anal (CCE) aumentó drásticamente, es de 35/100.000 habitantes en los hombres que tienen sexo con hombres (HSH), similar a la del cáncer del cuello uterino antes del Papanicolaou (PAP). En forma análoga a la pesquisa del cáncer cervical, el PAP anal y la anoscopía de alta resolución (AAR), se utilizan para la detección temprana de las lesiones precursoras del CCE. Objetivo: Evaluar los hallazgos de la citología anal y la AAR en una población de alto riesgo para desarrollar displasia y CCE. Diseño: Observacional, descriptivo, transversal, prospectivo. Población: Pacientes de alto riesgo (individuos HIV positivos, hombres que tienen sexo con hombres (HSH), mujeres con antecedentes de cáncer o displasia del tracto genital inferior, individuos con antecedentes de HPV anal o genital) que concurrieron al Consultorio de Detección Temprana de la Displasia Anal, entre 1 abril y 30 junio 2012. Método: Tacto rectal, anoscopía convencional, PAP anal y AAR, con biopsia dirigida de lesiones sospechosas. Comparación de la citología con la histología...

Background: The incidence of anal squamous cell carcinoma (SCC) has increased dramatically, with an incidence of 35/100.000 inhabitants in men who have sex with men (MSM), similar to that of cervical cancer before the Papanicolaou (PAP). In analogy form to screening of cervical cancer, anal PAP and high resolution anoscopy (HRA) are used for early detection of SSC precursor lesions. Objective: To assess the findings of anal cytology and HRA in a high risk population for developing dysplasia and SCC. Design: Cross-sectional, descriptive, prospective, study. Population: High-risk patients (HIV- positive individuals, men who have sex with men, women with previous cancer or dysplasia of the lower genital tract, individuals with previous anal or genital condylomata) who attended the Anal Dysplasia Early Detection Clinic between April 1-June 30, 2012, were included. Methods: Digital rectal examination, conventional anoscopy, anal PAP and HRA, with biopsies of suspected areas was performed...

Cáncer de cabeza y cuello asociado al virus papiloma humano: revisión de la literatura / Head and neck cancer associated with human papilloma virus: literature review

Oral cavity and oropharyngeal squamous cell carcinoma is the sixth most common cancer worldwide and human papillomavirus (VPH) is proposed as an etiologic risk factor. In our country there is no prevalence studies of this virus either in oral or oropharyngeal mucosa. This data would be useful at the moment of evaluating the risk in general population of developing head and neck cancer VPH related and also the impact that it could have the proved effective vaccines against VPH...

Frecuencia de virus papiloma humano en tumores no ginecológicos de la Región de la Araucanía, Chile / Human papilloma virus frequency in non-gynecological tumors in the Araucanía Region, Chile

El Virus Papiloma Humano (HPV por sus siglas en inglés) es una de las infecciones de transmisión sexual más frecuentes del mundo y se encuentra presente en la mayoría de los cánceres de cuello uterino. Se ha descrito su presencia en otros tipos de cáncer no ginecológicos como lo son esófago y próstata. Sin embargo, las frecuencias de HPV descritas hasta el momento para estos tipos de cáncer son muy variables, y no hay artículos donde se muestren la presencia de HPV en estas neoplasias en Chile. El objetivo de este estudio fue determinar la frecuencia de HPV en muestras de biopsias de tumores no ginecológicos y tejido inflamatorio de pacientes de la región de La Araucanía. Se extrajo DNA desde un total de 47 biopsias de pacientes con esofagitis, 25 con carcinoma escamoso esofágico, 20 con hiperplasia nodular de la próstata y 39 con adenocarcinoma prostático. Estas fueron analizadas por PCR de la región L1 del virus y posterior genotipificación por reverse line blot. Se detectó HPV en el 53,2% de las muestras de esofagitis, 48% en muestras de carcinoma escamoso esofágico, 15% en hiperplasia nodular de la próstata y un 15,4% en los casos de adenocarcinoma prostático. Siendo los más frecuentes los genotipos de HPV 16 y 18, ya sea en infecciones simples o junto con otros genotipos, en lesiones preneoplásicas y neoplásicas de los tejidos estudiados. Existe una alta frecuencia de infección por HPV en biopsias de esofagitis y tejido inflamatorio esofágico de pacientes de la región de la Araucanía. En los casos de adenocarcinoma prostático e hiperplasia nodular de la próstata se observa una baja frecuencia de HPV.

Human Papilloma Virus (HPV) is the most common sexually transmitted disease in the world and it is present in practically all cervical cancers. Its presence was described in other types of non-gynecologic cancer such as esophageal and prostate. However, HPV frequency described for these cancers is highly variable, and there are no articles describing the presence of HPV in these tumors in Chile. To determine HPV frequency in samples from biopsies of non-gynecological tumors and inflammatory tissue from patients in the Araucanía region, DNA was extracted from a total of 47 biopsies from patients with esophagitis, 25 with esophageal squamous cell carcinoma, 20 with prostate nodular hyperplasia and 39 with prostate adenocarcinoma. These were analyzed by PCR of HPV L1 region and subsequent genotyping by reverse line blot. HPV was detected in 53.2% of esophagitis samples, 48% in esophageal squamous cell carcinoma, 15% in prostatitis and 15.4% in cases of prostatic adenocarcinoma. The most frequent HPV genotypes were 16 and 18, either single or in combination with other genotype infections, in inflammatory tissue and neoplastic lesions. In patients of the Araucanía region, there is a high rate of HPV infection in biopsies obtained in esophagitis and esophageal inflammatory tissue. In cases of prostatic adenocarcinoma and prostate nodular hyperplasia a low rate of HPV was observed.

Association of cutaneous malignancy with epidermodysplasia verruciformis: a clinicopathological study

To find out presence of nonmelanoma skin cancer [NMSC] in a series of 13 patients with diagnosis of epidermodysplasia verruciformis [EDV]. This prospective descriptive study detailed the clinical presentation of patients with EDV associated with nonmelanoma cutaneous malignancy between 2007 and 2010 presenting to Dermatology OPD Pakistan Institute of Medical Sciences, Islamabad. Patients were diagnosed on clinical basis. Patients with all ages and both sexes were included. Skin biopsies were taken from lesions with suspicion of malignancy, stained with hematoxylin and eosin and studied in collaboration with histopathologist. Different histopathological findings were recorded and results analyzed. 13 cases were studied for presence of NMSC. NMSC were found in 3 [23%] out of 13 patients. Actinic keratosis was found in 2 patients and one patient had seborrheic keratosis with suspicious lesions. The clinically suspicious lesions should always be biopsied, as cutaneous malignancy is a well-known, frequent and serious complication of EDV and there is high potential in these patients to develop premalignant conditions

Infecção pelo vírus Epstein-Barr tem influência sobre o desenvolvimento do carcinoma de laringe? Detecção de EBV pelo Real-Time Polymerase Chain Reaction em tecidos tumorais de pacientes com carcinoma de laringe / Does Epstein-Barr virus infection have an influence on the development of laryngeal carcinoma? Detection of EBV by Real-Time Polymerase Chain Reaction in tumour tissues of patients with laryngeal carcinoma

O vírus Epstein-Barr (EBV) é um conhecido vírus carcinogênico. A associação entre EBV e alguns tumores sugere que também pode haver correlação entre carcinoma de laringe e EBV. OBJETIVO: O presente estudo pretende determinar o papel do EBV na etiologia do carcinoma de laringe. MÉTODO: Estudo prospectivo sobre EBV por reação em cadeia da polimerase em tempo real em tecidos tumorais de 25 pacientes com carcinoma de laringe e 17 pacientes com lesões benignas de laringe; análise da relação entre presença de DNA viral e tabagismo, etilismo, localização e diferenciação tumoral. RESULTADOS: Não houve diferenças significativas entre os grupos de controle e de estudo para positividade da PCR para EBV (p > 0,05). Não foi identificada relação estatisticamente significativa entre positividade para EBV e diferenciação tumoral, localização da neoplasia, tabagismo ou etilismo (p > 0,05). CONCLUSÃO: Nossos resultados sugerem que, a despeito de sua identificação em alguns carcinomas espinocelulares de laringe, a presença de EBV não teve qualquer influência na patogenia do carcinoma de laringe.

Epstein-Barr virus (EBV) is a well-known carcinogenic virus, and the association of EBV with some tumours suggests that there may also be an association between laryngeal carcinoma and EBV. OBJECTIVE: The aim of this study is to determine the role of EBV in the aetiology of laryngeal carcinoma. METHOD: Prospective investigation the EBV with real time polymerase chain reaction in tumour tissues of 25 patients with laryngeal carcinoma and 17 patients with benign laryngeal lesions, and investigation of the relationship between the presence of viral DNA and patients' smoking habits, alcohol consumption, localization and differentiation of the tumour. RESULTS: There was no significant difference between the control group and patient group in terms of EBV polymerase chain reaction positivity (p > 0.05). Also we couldn't find a statistically significant relationship between EBV positivity and differentiation of the tumour, localization of the tumour, smoking and alcohol consumption habits (p > 0.05). CONCLUSION: Our results suggest that, although EBV is present in some of the squamous cell laryngeal carcinomas, its presence has no effect on the pathogenesis of laryngeal carcinomas.

Genótipos de vírus de papiloma humano em carcinoma de células escamosas de cabeça e pescoço na Colômbia / Human papillomavirus types in cases of squamous cell carcinoma of head and neck in Colombia

Estimar a prevalência de tipos do vírus de papiloma humano (HPV) em câncer de cabeça e pescoço (CCP) é relevante para se prever o impacto da vacina contra o HPV. OBJETIVO: Estimar a prevalência global, por gênero e idade, do vírus do HPV em CCP. MÉTODO: Estudo transversal, retrospectivo envolvendo quatro laboratórios de patologia de Medellín, Colômbia. O exame utilizado foi o PCR GP5+/6+ e hibridização reversa. Além disso, os HPV 16 e 18 foram identificados utilizando-se PCR específica para esses tipos. RESULTADOS: Foram incluídos 175 casos primários de CCP, consecutivamente diagnosticados entre 1999 e 2008, com diagnóstico confirmado e DNA amplificado. A prevalência de HPV foi de 18,9%. O HPV foi encontrado em 23,9%, 17,5% e 13,3% dos casos de cavidade oral, laringe e orofaringe, respectivamente. Entre os casos de VPH+, 82% foram HPV 16 e 18% HPV18. A maioria dos casos foi de pessoas do sexo masculino. Nos homens, a idade de diagnóstico foi menor do que nas mulheres, principalmente naqueles de acometimento na cavidade oral. CONCLUSÃO: Os HPV 16 e 18 foram encontrados em quase 20% desses casos de CCP. O impacto da vacinação contra o HPV para a prevenção desse câncer na população merece maiores estudos.

Estimating the type-specific prevalence of human papillomavirus (HPV) in head and neck cancer (HNSCC) is helpful in predicting the impact of HPV immunization. OBJECTIVE: To estimate the overall prevalence, and gender and age-specific prevalence of HPV in HNSCC. METHOD: This cross sectional retrospective study was carried out in four pathology laboratories of Medellin, Colombia. HPV testing was performed by GP5+/6+ PCR-based RLB and HPV 16 and 18 type-specific PCR. RESULTS: 175 primary HNSCC cases consecutively diagnosed between 1999 and 2008 with confirmed diagnosis and amplifiable DNA were included. Overall HPV prevalence was 18.9%. HPV was found in 23.9%, 17.5% and 13.3% of the oral cavity, larynx and oropharynx cases respectively. Among HPV positive cases, 82% were HPV 16 and 18% were HPV 18. No other HPV genotypes were identified. Most patients were males. Male patients were younger that their female counterparts, particularly in oral cavity cancer cases. CONCLUSION: HPV 16 and 18 genotypes were found in nearly 20% of HNSCC cases in Colombian patients. The impact of HPV vaccination for the prevention of HNSCC in this population deserves further evaluation.

Human papillomavirus genotypes in invasive cervical squamous cell carcinoma in Trinidad / Genotipos de virus de los papilomas humanos en carcinoma cervicouterino escamocelular invasor en Trinidad

OBJECTIVE: To determine the relative contribution of known high-risk human papillomavirus (HPV) genotypes to the occurrence of cervical cancers in Trinidad. METHODS: The distribution of HPV genotypes in cases of invasive cervical squamous cell carcinoma in Trinidad was investigated. This study was a follow-up to an investigation of HPV genotypes in 310 nonsymptomatic women in Trinidad. The latter study showed that cervical HPV prevalence and heterogeneity of genotypes were high in the study population; notably, the genotypes targeted by the available HPV prophylactic vaccines were not the most common types. RESULTS: The current study of 85 cases of invasive cervical squamous cell carcinomas demonstrated that the previously observed heterogeneity in HPV genotype distribution is lost in cases of invasive cervical cancer, with the vaccine-targeted HPV types HPV 16 and HPV 18 becoming the most prevalent. CONCLUSIONS: HPV 16 and HPV 18 were the primary HPV genotypes associated with cases of invasive squamous cell carcinoma in the current Trinidad study. This strong association leads us to conclude that the HPV vaccines targeting HPV 16 and HPV 18 may contribute to reducing the cervical cancer burden in Trinidad.

OBJETIVO: Determinar la contribución relativa de los diferentes genotipos de virus de los papilomas humanos (VPH) conocidos como de alto riesgo para la aparición de cáncer cervicouterino en Trinidad. MÉTODOS: Se investigó la distribución de los genotipos de VPH en casos de carcinoma cervicouterino escamocelular invasor en Trinidad. Este estudio fue la continuación de una investigación de los genotipos de VPH presentes en 310 mujeres asintomáticas en Trinidad. Este último estudio reveló altas prevalencia de VPH en el cuello uterino y heterogeneidad de los genotipos en la población del estudio; cabe destacar que los genotipos a los que se dirigen las vacunas preventivas de la infección por VPH disponibles no fueron los tipos más frecuentes. RESULTADOS: El presente estudio, llevado a cabo en 85 casos de carcinoma cervicouterino escamocelular invasor, demostró que la heterogeneidad anteriormente observada en la distribución de genotipos de VPH no se mantiene en los casos de cáncer cervicouterino invasor, y que los tipos de VPH objeto de la vacuna, el VPH 16 y el VPH 18, pasan a ser los más prevalentes. CONCLUSIONES: En el presente estudio llevado a cabo en Trinidad, el VPH 16 y el VPH 18 fueron los principales genotipos de VPH asociados con los casos de carcinoma escamocelular invasor. Esta estrecha asociación nos lleva a la conclusión de que las vacunas contra el VPH dirigidas contra el VPH 16 y el VPH 18 pueden contribuir a la reducción de la carga de cáncer cervicouterino en Trinidad.

Impact of HPV infection on the development of head and neck cancer

Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is considered to be a distinct clinical entity with better prognosis than the classical tobacco- and alcohol-associated tumors. The increasing incidence of this neoplasia during the last decades highlights the need to better understand the role of HPV in the development of these cancers. Although the proportion of HNSCC attributed to HPV varies considerably according to anatomical site, overall approximately 25% of all HNSCC are HPV-DNA positive, and HPV-16 is by far the most prevalent type. In this review we discuss the existing evidence for a causal association between HPV infection and HNSCC at diverse anatomical head and neck subsites.