Genotipificación de VPH en papilomas orales de pacientes con infección por VIH del Hospital San Juan de Dios / HPV genotypes in oral papilloma in Hospital San Juan de Dios HIV (+) patients

Resumen Introducción: Pacientes con infección por VIH presentan mayor riesgo de infecciones orales con genotipos de virus papiloma humano (VPH) de alto riesgo oncogénico (VPH-AR). Objetivo: Determinar los genotipos de VPH en lesiones papilomatosas orales de pacientes con infección por VIH y describir los factores clínicos, histopatológicos y recuento de linfocitos T CD4+ y carga viral asociados. Métodos: Se estudiaron ocho sujetos adultos con infección por VIH y lesiones papilomatosas por VPH. Se extrajo el ADN de la lesión y se detectó el genoma y los genotipos de VPH mediante reacción de polimerasa en cadena e hibridación con el kit comercial HPV 3.5 LCD-Array (Chipron®) y se describieron factores asociados. Resultados: El 63% de los pacientes exhibió más de un genotipo de VPH y 75% de ellos exhibió al menos un genotipo VPH-AR. El genotipo más frecuente fue el VPH 52 (27%), seguido del VPH16 y 56 (18%). El recuento medio de linfocitos T CD4+ en pacientes con al menos un genotipo VPH-AR fue de 330,6 céls/mm3. Conclusiones: Se detectó una mayor frecuencia de infecciones múltiples por VPH, incluido al menos un genotipo de alto riesgo. El genotipo VPH-AR 52 fue el más frecuente. El recuento medio de LT CD4+ en pacientes que presentan al menos un genotipo VPH-AR indica una inmunosupresión moderada. Se requiere aumentar el número de pacientes.

Background: HIV (+) patients have a higher risk of oral infections with high oncogenic risk HPV (HPV-HR). Aim: To determine the HPV genotypes in oral papillomatous lesions in HIV (+) patients and describe the associated factors. Methods: Eight adults HIV (+) subjects with papillomatous HPV lesions were studied. The lesions DNA was extracted and HPV genome and genotypes were detected by PCR and the commercial kit HPV 3.5 LCD-Array Kit (Chipron®) and associated factors were described. Results: 63% of patients exhibited more than one HPV genotype and 75% of them exhibited at least 1 HPV-HR genotype. The most frequent genotype was HPV 52 (27%), followed by HPV 16 and 56 (18%). The mean CD4 T lymphocyte count in patients with at least one HPV-HR genotype was 330.6 cells/mm3. Conclusions: A higher frequency of multiple HPV infections was detected, including at least one high-risk genotype. The genotype HPV-AR 52 was the most frequent. The mean CD4 T lymphocyte count in patients with at least one HPV-HR genotype indicates moderate immunosuppression. It is required to increase the number of patients.

Susceptibilidad genética frente al cáncer bucal por infección del virus del papiloma humano / Genetic susceptibility to oral cancer due to human papillomavirus infection

Resumen Los carcinógenos ambientales y el virus del papiloma humano (VPH) son los principales responsables del cáncer bucal. Los factores de susceptibilidad en el genoma humano desempeñan un papel modulador del riesgo, sin embargo, no todos los individuos expuestos a los carcinógenos padecen cáncer. El objetivo de la presente revisión es describir los principales factores de susceptibilidad genética para cáncer bucal en individuos con infección por VPH. Se realizó una búsqueda sistemática en tres bases de datos en inglés; solo siete artículos cumplieron con los criterios de selección. Se registraron polimorfismos genéticos en tres categorías relacionados con el VPH y que participan en la oncogénesis. Se identificaron tres artículos relativos a la desregulación de los mecanismos de control del ciclo celular, uno relativo a mutaciones en la vía de la apoptosis y tres a polimorfismos en genes de respuesta inflamatoria e inmune. La asociación entre polimorfismos para el desarrollo de cáncer bucal y VPH es evidente, aunque continúa en estudio ya que no siempre el patrón de oncogénesis de las neoplasias bucales está relacionado con el VPH, sino con otros factores ambientales o epigenéticos.

Abstract Environmental carcinogens and human papillomavirus (HPV) are the main responsible factors for oral cancer. Susceptibility factors in the human genome play a risk-modulating role; however not all individuals exposed to these carcinogens suffer from cancer. The purpose of the present review is to describe the main factors of genetic susceptibility to oral cancer due to HPV infection. A systematic search was carried out in three databases in English, with only 7 articles meeting the selection criteria. Genetic polymorphisms are shown in three categories, which are related to HPV and participate in oncogenesis. Three articles related to deregulation of cell cycle control mechanisms were identified, as well as one referring to mutations in the apoptosis pathway and three about polymorphisms in inflammatory and immune response genes. The association of polymorphisms for the development of oral cancer by HPV is evident, although it remains under study. Oral neoplasms’ oncogenesis pattern is not always associated with HPV, but with other environmental or epigenetic factors.

Oral and oropharyngeal cancer: epidemiology and survival analysis / Câncer de boca e orofaringe: epidemiologia e análise da sobrevida

ABSTRACT Objective To evaluate the epidemiological profile and survival rate of oral and oropharyngeal cancer patients seen at a university hospital. Methods A cross-sectional study was carried out by means of the pathological reports of patients with oral and oropharyngeal cancer, seen at a university hospital of the Southern Region, between January 2004 and December 2014. Information was collected on patients and tumors. The mortality rate was gathered from the patient death registry in the Mortality Information System. Data were analyzed using the Kaplan-Meier survival curve and the log-rank test to compare variables. Results The 5- and 10-year survival rates were 42% and 38%, respectively. The anatomical location had a significant association with survival rate (p=0.001), with the rates were better in the lips (p=0.04), and worse in the oropharynx (p=0.03). There were no statistically significant differences between survival rates according to age, sex, ethnicity, schooling level and histologic grade. Conclusion The survival rates of oral and oropharyngeal cancer were and associated with the anatomical site of the tumor.

RESUMO Objetivo Avaliar o perfil epidemiológico e a taxa de sobrevida do câncer de boca e orofaringe de pacientes atendidos em um hospital universitário. Métodos Foi realizado um estudo transversal por meio dos laudos anatomopatológicos dos pacientes com câncer de boca e orofaringe atendidos em um hospital universitário, na Região Sul, entre janeiro de 2004 a dezembro de 2014. A partir destes laudos, foram coletadas informações sobre o paciente e o tumor. A taxa de mortalidade foi obtida do registro de óbitos dos pacientes no Sistema de Informações sobre Mortalidade. Os dados foram analisados utilizando a curva de sobrevida pelo método de Kaplan-Meier e o teste de log-rank para a comparação das variáveis. Resultados As taxas de sobrevida em 5 e 10 anos foram 42% e 38%, respectivamente. A localização anatômica apresentou associação significativa com a taxa de sobrevida (p=0,001), sendo que, em lábio, os índices foram melhores (p=0,04) e, em orofaringe, piores (p=0,03). Não houve diferenças estatisticamente significantes entre as taxas de sobrevida de acordo com idade, sexo, etnia, nível educacional e grau histológico. Conclusão As taxas de sobrevida do câncer de boca e orofaringe foram baixas e associadas à localização anatômica do tumor.

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.

Oral plasmablastic lymphoma as the first manifestation of AIDS

Abstract Plasmablastic lymphoma is a non-Hodgkin lymphoma characterized by its plasmacytic differentiation and predilection for the oral cavity. It is among the lymphomas most commonly associated with AIDS. This report details a case of a HIV-positive patient with a 1-month history of an exophytic mass in the gingival area of the upper left quadrant. The diagnosis of plasmablastic lymphoma was made based on its histopathological and immunophenotypical features. She was treated with chemotherapy followed by autologous hematopoietic stem cell transplantation. Despite complete resolution of the lesion, the patient died of cardiorespiratory arrest. This case illustrates plasmablastic lymphoma as the first clinical manifestation of AIDS, highlighting the importance of differentiating between a potentially malignant lesion and other pathologic processes.

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.

Comparative study between biopsy and brushing sampling methods for detection of human papillomavirus in oral and oropharyngeal cavity lesions, / Estudo comparativo entre biópsia e escovado na pesquisa do papilomavírus humano em lesões de cavidade oral e de orofaringe

ABSTRACT INTRODUCTION: Many epidemiological studies have suggested that human papillomavirus (HPV), especially type 16, is involved in the genesis of squamous cell carcinoma of the oral cavity and oropharynx, especially in young, non-smoking patients; thus, its detection in lesions in this region is important. OBJECTIVE: To clarify the capacity of the brushing sampling method to detect the presence of HPV in oral or oropharyngeal lesions through polymerase chain reaction (PCR) testing, and to compare the results with those obtained by biopsy. METHODS: Prospective study of adult patients with oral or oropharyngeal lesions assessed by PCR, comparing biopsy specimens with samples obtained by the brushing method. The study was approved by the Research Ethics Committee of the institution. RESULTS: A total of 35 sample pairs were analyzed, but 45.7% of the brushing samples were inadequate (16/35) and, thus, only 19 pairs could be compared. There was agreement of results in 94.7% (18/19) of the pairs, with HPV identified in 16 of them. HPV DNA was detected in 8.6% (3/35) of biopsy and 5.7% (2/35) of brushing samples. CONCLUSION: There was no statistically significant difference between the two methods, but the brushing sampling method showed a higher number of inadequate samples, suggesting that it is an unreliable method for surveillance.

Resumo INTRODUÇÃO: Muitos estudos epidemiológicos indicam a participação do papilomavírus humano, especialmente o tipo 16, na carcinogênese dos tumores espinocelulares das cavidade oral e oro-faríngea, principalmente em jovens e não fumantes, sendo portanto importante sua detecção nas lesões desta região. OBJETIVO: Elucidar a habilidade do escovado em detectar o papilomavírus humano, pela reação em cadeia da polimerase, nas lesões orais e orofaríngeas, comparando os resultados com os obtidos por biópsia. MÉTODO: Estudo prospectivo de pacientes com lesões orais e orofaríngeas, pela reação em cadeia da polimerase, no qual foram pareados os resultados de amostras obtidas por escovado e por biópsia. A pesquisa foi aprovada pelo Comitê de Ética em Pesquisa da instituição. RESULTADO: Foram analisados 35 pares de amostras, porém estavam inapropriadas para análise 45,7% (16/35) das amostras obtidas por escovado, e portanto, somente 19 pares puderam ser comparados. Em 94,7% dos pares houve concordância dos resultados, sendo encontrado o papilomavírus humano − 16 em um destes pares. O ácido desoxirribonucleico do papilomavírus humano foi detectado em 8,6% (3/35) das biópsias e em 5,7% (2/35) dos escovados. CONCLUSÃO: Não houve diferença estatística entre os métodos, mas como houve um grande número de amostras obtidas por escovado inapropriadas, este parece não ser confiável para o rastreamento.

Virus papiloma humano en cáncer oral y orofaríngeo: revisión de la literatura / Human papilloma virus in oral and oropharyngeal cancer: review of the literature

Estudios recientes demuestran una realidad prácticamente ineludible que manifiesta que el Virus Papiloma Humano (VPH) puede estar asociado al desarrollo del Carcinoma de Células Escamosas en cavidad oral y orofarínge. Desde el descubrimiento en 1974 por parte de zur Hausen et al., quienes ayudaron a definir el mecanismo por medio del cual el VPH provoca la transformación del queratinocito normal a un estado maligno, han sido numerosos los estudios que han descrito la presencia del VPH en carcinomas de cabeza y cuello, específicamente en cavidad oral y orofarínge. La detección del virus en estos carcinomas podría tener implicaciones clínicas importantes en el pronóstico y tratamiento de estos tumores, con resultados más favorables para el paciente; así mismo, justificar planes de prevención orientados al diagnóstico temprano y a la protección específica contra el VPH. Actualmente están en desarrollo terapias experimentales mínimamente invasivas que potencian el sistema inmunitario para atacar estos tumores, sin embargo, aún no están aprobadas para su uso general. En Chile todavía no existen estudios que describan la situación actual del VPH con respecto al Carcinoma de Células Escamosas en cavidad oral y orofarínge que pudieran orientar al sistema de salud con respecto a la prevención y tratamiento de este tipo de cáncer. En esta revisión presentamos los principales aspectos que relacionan al virus con este tipo de carcinoma. Se revisaron artículos indexados en inglés (Pubmed, Scopus, Cochrane Library, Google Scholar) y español (SciELO, Google Scholar), con el objetivo de brindar al Odontólogo general y especialistas una información actualizada sobre este tema, tanto desde su epidemiología como desde los mecanismos de acción carcinogénica del virus, técnicas de diagnóstico avanzadas, además, formas de prevención y estado del arte en materia de tratamiento.

Recent studies indicate what has become a nearly inescapable reality in that Human Papilloma Virus can be associated to the development of Oral and Oropharyngeal Squamous Cell Carcinoma. Since the discovery of zur Hausen et al. that helped define the mechanism by which HPV causes normal keratinocyte transformation to a malignant state, there have been numerous studies that have described the presence of HPV in head and neck carcinomas, specifically in oral cavity and oropharynx. The detection of the virus in these carcinomas may have important clinical implications in the prognosis and treatment of these tumors with more favorable patient outcomes; likewise, justify prevention plans aimed at early diagnosis and specific protection against HPV. Currently minimally invasive experimental therapies that boost the immune system to attack these tumors are in development, however, they are not yet approved for general use. In Chile there are no studies that describe the current situation with regard to HPV Squamous Cell Carcinoma in oral cavity and oropharynx that may guide the health system regarding the prevention and treatment of this cancer. In this review we present the principal aspects that associate the virus with this type of oral and oropharyngeal carcinoma. We reviewed indexed articles in English (Pubmed, Scopus, Cochrane Library, Google Scholar) and Spanish (SciELO, Google Scholar), with the objective to provide Dental Surgeons and specialists the most updated information about this subject. The review was developed considering the epidemiology as well as the carcinogenic mechanisms of the virus, advanced diagnostic techniques, ways of prevention and state of the art in treatment matters.

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.

Oral conditions associated with hepatitis C virus infection

Hepatitis C virus [HCV] infection in more than 170 million chronically infected patients with no developed preventive vaccine is a globally important issue. In addition to expected hepatic manifestations, a number of extrahepatic manifestations, such as mixed cryoglobulinemia, glomerulonephritis, polyarteritis nodosa, rashes, renal disease, neuropathy, and lymphoma, have been reported following HCV infection, which are believed to be influenced by the virus or the host immune response. HCV combination therapy with pegylated interferon and ribavirin might be associated with side effects as well. The association of HCV with special oral conditions has also been reported recurrently; the mechanism of most of which remains unclear. This article reviews the association of HCV infection with some of the oral conditions such as oral health, Sjogren's syndrome, lichen planus and oral cancer.

O papel do Epstein Barr vírus na carcinogênese oral / The role of Epstein Barr virus in oral carcinogenesis

Introdução: o carcinoma espinocelular (CEC) é o câncer de cabeça e pescoço de maior ocorrência, representando cerda de 90% de todos esses tumores. O CEC apresenta diversos fatores de risco, como fumo, álcool, e alguns vírus de potencial oncogênico, entre eles o Epstein Barr vírus (EBV) que é um membro da família Herpesviridae e apresenta um tropismo por linfócitos B e também por células epiteliais. Objetivo: realizar um levantamento na literatura da presença do EBV em carcinomas orais. Conclusão: o EBV está intimamente relacionado com carcinoma de nasofaringe, um CEC de alta ocorrência no sudeste asiático, no entanto o seu papel nos demais CEC orais ainda não foi comprovado.

Introduction: the squamous cell carcinoma (SCC) is the head and neck cancer of higher occurrence, representing about 90% of all these tumors. The SCC has several risk factors as smoking, alcohol and some oncogenic viruses, including the EpsteinBarr virus (EBV). The EBV is a member of Herpesviridae family and has tropism for B lymphocytes and also for epithelial cells. Aim: the aim of this study was accomplish a review of the literature about the presence of the EBV in oral carcinomas. Conclusion: EBV is closely related to nasopharyngeal carcinoma, a SCC of high incidence in Southeast Asia, however its role in others oral SCC has not been proved.

Immunophenotyping of HPV types 16 and 18 among Sudanese patients with oral lesions

The aim of this study was to screen patients with oral lesions for the presence of Human Papilloma Virus [HPV] types 16 and 18. Sixty patients aged between 11-80 years with a mean age of 46 years were examined using immunohistological techniques. All samples were retrieved from RICK during the period from August 2009 to August 2010. Out of 60 patients, 50 had Oral Squamous Cell Carcinomas [OSCCs] and the remaining ten had benign oral lesions, included as internal control. Of the 50 patients with OSCCs, 10 [20%] showed positive immunohistochemical results for HPV types 16 and 18 of which 50% were detected among males and 50% were demonstrated among females. The ten positive findings were Immunophenotyped as follows: five were positive with HPV type 16, four with type 18 and one was positive for HPV types 16 and18. All patients with benign oral lesions were negative for HPV immunohistochemistry. The study suggests the role of HPV 16 and 18 in the etiology of oral cancers in different parts of Sudan. However, the use of molecular techniques such as PCR are needed to confirm the results of immunohistochemistry in the role of the HPV in developing of OSCC in Sudan

Immunohistochemical staining of Langerhans cells in HPV-positive and HPV-negative cases of oral squamous cells carcinoma

The Human Papillomavirus (HPV) has been strongly implicated in development of some cases of oral squamous cell carcinoma (OSCC). However, the immunological system somehow reacts against the presence of this virus. Among the cells involved in such mechanism of defense Langerhans cells (LC) stand out, which are responsible for processing and presenting antigens. OBJECTIVES: The purposes of this study were to investigate the presence of HPV DNA and to evaluate the immunohistochemical reactivity for Langerhans cells between HPV-positive and HPV-negative OSCC. Twenty-seven cases of OSSC were evaluated. MATERIAL AND METHODS: DNA was extracted from paraffin-embedded tissue samples and amplified by Polymerase Chain Reaction (PCR) for the detection of HPV DNA. Viral typing was performed by dot blot hybridization. Immunohistochemistry was performed by the Streptavidin-biotin technique. RESULTS: From the 27 cases, 9 (33.3 percent) were HPV-positive and 18 (66.0 percent) HPV-negative. HPV 18 was the most prevalent viral type (100 percent cases) and infection with HPV-16 (co-infection) was detected in only 1 case. In the OSCC specimens examined, immunoreactivity to S-100 antibody was detected in all cases, with a mean number of 49.48±30.89 Langerhans cells positive for immunostaining. The mean number of immunostained Langerhans cells was smaller in the HPV-positive cases (38 cells/case) than in the HPV-negative cases (42.5 cells/case), but this difference was not significant (p=0.38). CONCLUSIONS: The low frequency of detection of HPV DNA in OSCC indicates a possible participation of the virus in the development and progression of only a subgroup of these tumors. There was no association between the immunohistochemical labeling for Langerhans cells (S-100+) and HPV infection of in OSSC. These findings suggest that the presence of HPV in such OSCC cases could not alter the immunological system, particularly the Langerhans cells.

Papiloma invertido (Papiloma Schneideriano) com envolvimento da cavidade oral: relato de caso incomum / Inverted papilloma (Schneiderian papilloma) with involvement of the oral cavity: report of an unusual case

O papiloma invertido schneideriano é uma neoplasia de origem no epitélio de revestimento que surge da mucosa respiratória revestindo a cavidade nasal e os seios paranasais. Frequentemente, surge como uma lesão unilateral no septo nasal e estende-se secundariamente para o nariz e os seios paranasais. Este trabalho relata um caso incomum desta patologia, com o envolvimento da cavidade oral em um homem branco, de 61 anos de idade, cuja avaliação clínica revelou uma massa vegetante no rebordo alveolar direito da maxila, com duração de aproximadamente 4 meses. Após avaliação radiográfica, constatouse o envolvimento do seio maxilar. A análise microscópica, hibridização in situ e análise imunoistoquímica da peça cirúrgica levaram a um diagnóstico de displasia moderada em PIS associado à infecção por HPV.

Inverted Schneiderian papilloma (ISP) is a neoplasm of epithelial lining origin which arises in the respiratory mucosa that lines the nasal cavity and paranasal sinuses. The inverted Schneiderian papilloma frequently appears as a unilateral lesion in the nasal septum and extends secondarily to the nasal and paranasal sinuses. This paper reports an unusual case of this pathology with involvement of the oral cavity in a 61-year-old white man. Clinical evaluation revealed a vegetating mass in the alveolar ridge of the right maxilla that had been present for approximately 4 months. After radiographic evaluation, involvement of the maxillary sinus was detected. Microscopic evaluation, in situ hybridization and immunohistochemical analysis of the specimen led to a diagnosis of ISP moderate dysplasia associated with HPV infection.

Detection of HPV DNA and immunohistochemical expression of cell cycle proteins in oral carcinoma in a population of brazilian patients

This study investigated the presence of human papillomavirus (HPV) DNA and viral types in 33 cases of oral squamous cells carcinoma (OSCC) and compared the immunohistochemical expression of the cell-cycle markers p21 and pRb between cases of the disease with and without HPV. DNA was extracted from paraffin-embedded tissue and amplified by PCR for the detection of HPV DNA. Viral typing was performed by dot blot hybridization. Immunohistochemistry was performed by the streptavidinbiotin technique. HPV DNA was detected in 11 (33.33 percent) of the 33 cases. The prevalent viral type was HPV 18 (81.81 percent). A significant association was observed between the presence of HPV and immunohistochemical expression of pRb, but not between p21 expression and the presence of the virus. The low frequency of detection of HPV DNA in OSCC suggests a possible participation of the virus in the development and progression of only a subgroup of these tumors.

Análise comparativa da proliferação celular entre carcinomas de células escamosas orais HPV-positivos e HPV-negativos / Comparative analysis of the cellular proliferation between HPV-positive and HPV-negative oral squamous cell carcinomas

INTRODUÇÃO: O carcinoma de células escamosas oral (OSCC) representa a neoplasia maligna mais freqüente em boca, e, entre os agentes etiológicos implicados, o papilomavírus humano (HPV) tem sido extensivamente estudado nos últimos anos. OBJETIVO: Analisar comparativamente os índices de proliferação celular em OSCCs HPV-negativos e HPV-positivos. MATERIAL E MÉTODO: A amostra consistiu em 11 casos de OSCCs HPV-positivos (10 infectados por HPV-18 e um por HPV-16 e 18) e 13 HPV-negativos, previamente analisados quanto à presença ou ausência, bem quanto à tipagem viral por proteína C reativa (PCR) (primers GP5+/GP6+) e hibridização dot blot, respectivamente. No método imunoistoquímico utilizou-se a técnica da estreptoavidina-biotina, com anticorpo para a proteína nuclear Ki-67. RESULTADOS: O teste estatístico não-paramétrico de Mann-Whitney revelou que não houve diferença estatisticamente significativa entre os grupos HPV-positivo e HPV-negativo (p = 0,72). Discussão: Os estudos semelhantes a estes são poucos e não são concordantes em demonstrar maior atividade proliferativa tumoral nos casos HPV-positivos em relação aos HPV-negativos, seja através da análise da expressão de proteínas relacionadas ao ciclo celular, seja na análise direta da fração proliferativa tumoral. CONCLUSÃO: Não houve diferença no índice de proliferação celular entre os grupos de OSCCs HPV-positivo e HPV-negativos.

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) is the most common malignant tumor in the mouth, and the human papillomavirus (HPV) has been hardly studied as a possible etiologic agent. OBJECTIVES: The aim of this study was to compare the rates of cell proliferation in HPV-positive and HPV-negative OSCC, using the immunohistochemical antibody Ki-67. MATERIAL AND METHOD: The sample consisted of 11 cases HPV-positive OSCC (10 cases infected with HPV-18 and 1 case infected with HPV-16 and 18) and 13 cases HPV-negative OSCCs, previously analyzed regarding the presence or absence of HPV, as well as the viral type, using PCR (primers GP5+/GP6+) and dot blot hybridization, respectively. Immunohistochemical study was performed by streptoavidin-biotin technique with antibody against nuclear protein Ki-67. RESULTS: The mean of positivity index of the HPV-positive OSCC (17.7 percent) was greater than HPV-negative OSCC (14.2 percent), however the statistic analysis showed that standard deviation in both groups was very high, almost equal the mean (14 percent and 9.5 percent, respectively). The Mann-Whitney non-parametric statistic test disclosed that there wasn't a significantly statistical difference between the groups. DISCUSSION: Similar studies to these are few and they are not concordant in demonstrating a bigger tumoral proliferative activity in those cases infected by HPV in relation to those not infected, either through the analysis of the protein expression related to the cellular cycle as in the direct analysis of the tumoral proliferative fraction. CONCLUSION: There were not differences in the rates of cell proliferation between the HPV-positive and HPV-negative grups.

Human papillomavirus in oral lesions / Virus papiloma humano en lesiones orales

Growing evidence suggests a role for human papillomavirus (HPV) in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases); the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell samples from normal oral mucosa were used as controls. HPV detection and typing were performed by polymerase chain reaction (PCR) using primers MY09, 11, combined with RFLP or alternatively PCR using primers GP5+, 6+ combined with dot blot hybridization. HPV was detected in 91.0% of HPV- associated benign lesions, 14.3% of non-HPV associated benign lesions, 51.5% of preneoplasias and 60.0% of cancers. No control sample tested HPV positive. In benign HPV- associated lesions, 30.0% of HPV positive samples harbored high-risk types, while in preneoplastic lesions the value rose to 59.9%. In cancer lesions, HPV detection in verrucous carcinoma was 88.9% and in squamous cell carcinoma 43.8%, with high-risk type rates of 75.5% and 85.6%, respectively. The high HPV frequency detected in preneoplastic and neoplastic lesions supports an HPV etiological role in at least a subset of oral cancers.

Crecientes evidencias sugieren que el virus Papiloma humano (HPV) tiene un rol en el cáncer oral; sin embargo su participación es todavía controvertida. Este estudio evalúa la frecuencia de ADN de HPV en una variedad de lesiones orales de pacientes de Argentina. Se seleccionaron 77 muestras de tejido oral de 66 pacientes (casos); el diagnóstico histo-patológico correspondió a: 11 lesiones benignas asociadas a HPV, 8 lesiones benignas no asociadas a HPV, 33 lesiones premalignas y 25 cánceres. Como controles se usaron 60 muestras de células exfoliadas de mucosa oral normal. La detección y tipificación de HPV se realizó por PCR empleando los primers MY09,11, seguida de RFLP, o PCR usando los primers GP5+, 6+ seguida de hibridación en dot blot. HPV fue detectado en 91% de las lesiones benignas asociadas a HPV, 14.3% de las lesiones benignas no asociadas, 51.5% de preneoplasias y 60% de cánceres. Ninguna muestra control resultó HPV positiva. En las lesiones benignas, 30% de las muestras HPV positivas correspondieron a tipos de alto riesgo, mientras que en las lesiones preneoplásicas la positividad ascendió a 59.9%. En cánceres, la detección de HPV en carcinomas verrugosos fue 88.9% y en carcinomas escamosos 43.8%, con 75.5% y 85.6% de tipos virales de alto riesgo, respectivamente. La alta frecuencia de HPV detectada en lesiones preneoplásicas y cánceres apoya un rol etiológico del HPV en, al menos, un subgrupo de cánceres orales.

Polymerase chain reaction; detection of human papilloma virus [HPV] type - 16 and 18 infection in laryngeal and oral squamous cell carcinoma in southern Iran

One fifth of cancers world wide are associated with viral infection. Epidemiologic and biomolecular evidence suggested that Human Papilloma Virus [HPV] infection may be associated with the development of head and neck cancer. [1] To clarify the role of HPV infection in head and neck cancers. [2] To evaluate the presence of HPV DNA in laryngeal and oral squamous cell carcinoma in southern Iran and comparison of results with studies in other regions Department of Otolaryngology-Head and Neck Surgery, Khallili Hospital, Shiraz Medical University Iran From 2003 to 2006. Eighty three [83] patients with Squamous Cell Carcinoma [SCC] of the larynx, 40 patients with benign mucosal lesion of the larynx [control], 47 patients with SCC of oral cavity and 10 patients with benign oral lesion were studied for the presence, of HPV DNA by Polymerase Chain Reaction [PCR]. None of the laryngeal SCCs or control group was positive for HPV DNA. Only 3/47 specimens from oral SCC were positive for HPV DNA. Oral control group was negative for HPV DNA. The present work suggests that HPV infection has not important role in carcinogenesis of laryngeal or oral SCC in southern Iran. However a multi center case-control study is needed to clarify this association

HPV in oral squamous cell carcinomas of a Brazilian population: amplification by PCR

O papilomavírus humano (HPV) constitui um grupo de vírus associados com lesões benignas e malignas do epitélio da pele e das mucosas. Alguns tipos de HPV, ditos oncogênicos, especialmente os HPVs 16 e 18, estão fortemente correlacionados com os cânceres cervical e anogenital, e também têm sido implicados na gênese do carcinoma epidermóide de boca. O objetivo deste estudo foi investigar a incidência de infecção pelo HPV, em 40 casos de carcinoma epidermóide de boca emblocados ou não em parafina, utilizando-se para isso a amplificação do DNA viral por PCR. Foram utilizados os iniciadores GP5+/GP6+, que amplificam parte da região L1 do vírus, comum a mais de 22 tipos de HPVs. Como controle positivo para as reações, foi utilizado um caso de condiloma, o qual foi positivo para os HPVs 16 e 18 na hibridização in situ. A amplificação para o HPV foi constatada apenas no controle positivo; nenhum dos casos de carcinoma epidermóide em estudo mostrou amplificação para o DNA viral. A ausência de amplificação de DNA do HPV nos casos de carcinoma epidermóide estudados sugere que esse vírus nem sempre participa do processo de carcinogênese. Essa diferença em relação a outros estudos provavelmente se dá por questões populacionais, ou mesmo de metodologia entre os diferentes trabalhos citados na literatura.