Infecção pelo HPV na região Sul do Brasil: uma revisão integrativa da literatura / HPV infection in southern Brazil: an integrative literature review / Infección por el VPH en el Sur de Brasil: una revisión integradora de la literatura

O papilomavírus humano (HPV) infecta pele e mucosas e causa, na grande maioria dos casos, lesões transitórias que podem evoluir para câncer. O objetivo deste estudo é avaliar, por meio de revisão integrativa, a literatura disponível sobre a frequência da infecção pelo HPV na região Sul do Brasil. Buscou-se nas bases de dados PubMed, Literatura Latino-americana e do Caribe em Ciências da Saúde (Lilacs) e Scientific Electronic Library Online (SciELO) a frequência de HPV na região Sul do Brasil nos últimos dez anos. Foram identificados oito estudos que se enquadraram nos critérios da pesquisa. A prevalência estimada de infecção pelo HPV foi de 46,19%. Os genótipos mais encontrados foram HPV 6, de baixo risco, e os subtipos HPV 16, HPV 18, HPV 31 e HPV 58, de alto risco. Nas amostras classificadas como LSIL/HSIL ou de células escamosas atípicas (ASC), tipos virais de baixo risco HPV 6, HPV 11 e HPV 44 foram os mais prevalentes, enquanto para os de alto risco os subtipos HPV 16, HPV 18 e HPV 58 foram os mais encontrados. Embora tenham sido identificados poucos estudos com essa temática nos últimos anos, a partir dos dados da pesquisa foi possível estimar a prevalência do HPV no Sul do Brasil e seus genótipos mais frequentes. Essa informação é importante para o planejamento das ações de saúde pública e dos serviços de saúde, contribuindo para a elaboração de estratégias de controle e prevenção da infecção.

Human Papillomavirus (HPV) infects skin and mucous membranes, and, in most cases, causes transient lesions that can progress to cancer. Given this scenario, this integrative review sought to evaluate the available literature on the frequency of HPV infection in southern Brazil. Bibliographic search was conducted on the PubMed, Latin American and Caribbean Literature on Health Sciences (Lilacs) and Scientific Electronic Library Online (SciELO) databases for papers on the frequency of HPV in southern Brazil published in the last ten years. Eight studies were identified. Estimate of HPV infection prevalence was 46.19%. Low-risk HPV 6 and high-risk HPV 16 were the most common genotypes, and HPV 18, HPV 31 and HPV 58 the most common subtypes. Risky viral types HPV 6, HPV 11 and HPV 44 were most prevalent in cellular changes classified as LSIL/HSIL or atypical squamous cell (ASC), whereas HPV 16, HPV 18 and HPV 58 prevailed as the high risk subtypes. Despite the small sample size of recent studies, the review was able to identified the prevalence of HPV infection in southern Brazil and its most common genotype, essential information for elaborating public health strategies and preventing infections.

El virus del papiloma humano (VPH) infecta la piel y las mucosas y, en la mayoría de los casos, provoca lesiones transitorias que pueden progresar a cáncer. El objetivo de este estudio es evaluar, a través de una revisión integradora, la literatura disponible sobre la frecuencia de infección por VPH en la región Sur de Brasil. Se realizaron búsquedas en las bases de datos PubMed, Literatura Latinoamericana y del Caribe en Ciencias de la Salud (Lilacs) y Scientific Electronic Library Online (SciELO) para determinar la frecuencia del VPH en la región Sur de Brasil en los últimos diez años. Se identificaron ocho estudios que cumplieron con los criterios de búsqueda. La prevalencia estimada de infección por VPH fue del 46,19%. Los genotipos más comunes fueron el VPH 6 de bajo riesgo y los subtipos VPH 16, VPH 18, VPH 31 y VPH 58 de alto riesgo. En muestras clasificadas como LSIL/HSIL o células escamosas atípicas (ASC), los tipos virales de bajo riesgo VPH 6, VPH 11 y VPH 44 fueron los más prevalentes, mientras que para los subtipos de alto riesgo VPH 16, VPH 18 y VPH 58 fueron los más frecuentes. Aunque se identificaron pocos estudios sobre este tema en los últimos años, con base en los datos de la encuesta, fue posible estimar la prevalencia del VPH en el Sur de Brasil y sus genotipos más frecuentes. Esta información es importante para planificar acciones de salud pública y servicios de salud, contribuyendo al desarrollo de estrategias de control y prevención de infecciones.

Lesão intraepitelial do colo uterino em adolescentes: como conduzir? / Intraepithelial lesions in adolescents: how to handle?

A atenção em saúde destinada a mulheres jovens, especialmente adolescentes, mostra-se um desafio, visto que, nesse grupo, apesar da maior incidência e prevalência de infecções genitais por HPV, há também maior probabilidade de regressão de lesões, com resolução espontânea na maioria das vezes. Frente a isto, surgem questionamentos quanto ao período ideal para início do rastreio do câncer de colo uterino e ao manejo das possíveis alterações citológicas. Em janeiro de 2016, o Instituto Nacional de Câncer (INCA) publicou a segunda edição, revisada e atualizada, das Diretrizes Brasileiras para Rastreamento do Câncer do Colo do Útero. Tal documento fornece as recomendações de rastreamento e seguimento para cada grupo de atipias citológicas, inclusive em populações especiais como adolescentes e gestantes. O presente artigo visa expor as recomendações no cuidado de adolescentes com citologia oncótica do colo uterino alterada, com base nas novas Diretrizes.(AU)

Health care for young women, especially adolescents, is challenging, since in this group, in spite of the higher incidence and prevalence of genital HPV infections, there is also a greater probability of regression of lesions, with spontaneous resolution in the majority of the times. Faced with this, questions arise regarding the ideal period for the beginning of cervical cancer screening and the management of possible cytologic alterations. In January 2016, the National Cancer Institute published the second, revised and updated edition of the Brazilian Guidelines for the Screening of Cervical Cancer. This document provides the recommendations for tracking and follow-up for each group of cytologic atypia, including in special populations such as adolescents and pregnant women. The present article aims to expose the recommendations in the care of adolescents with altered uterine cervical cytology, based on the new Guidelines.(AU)

Presence of highly oncogenic human papillomavirus in the oral mucosa of asymptomatic men

OBJECTIVES: The aim of this study was to identify highly oncogenic forms of human papillomavirus in the oral mucosa of asymptomatic men. METHODS: In this study, we analyzed samples of exfoliated cells from the oral cavity of 559 asymptomatic men. DNA-human papillomavirus was detected using the consensus primers PGMY09/11; viral genotyping was performed using type-specific PCR and restriction fragment length polymorphism. RESULTS: DNA-human papillomavirus was detected in 1.3% of the study participants and of those 42.8% were infected by more than one type of virus. Viral types included HPV6, 11, 89 (low oncogenic risk), and HPV52, 53 (high oncogenic risk). Increased vulnerability to human papillomavirus infection was observed in individuals aged over 26 years, among those who reported oral sex practices, and in those who have had more than 16 sexual partners since first engaging in sexual intercourse. CONCLUSIONS: There was a low prevalence of human papillomavirus detection in the oral mucosa of asymptomatic men. Highly oncogenic human papillomavirus types and infection by more than one viral type was observed. Oral sex practices and a large number of sexual partners may increase the risk of acquiring human papillomavirus infection. .

Identificación del papilomavirus humano en la leucoplasia bucal / Identification of the human papilomavirus in oral leukoplakia

Con el propósito de evaluar los resultados del diagnóstico clínico e histopatológico del papilomavirus humano asociado a la leucoplasia bucal, se efectuó un estudio descriptivo y transversal de 75 pacientes con la citada afección, tratados en la consulta estomatológica del Policlínico de Especialidades del Hospital Provincial Docente Clinicoquirúrgico "Saturnino Lora Torres" de Santiago de Cuba, desde septiembre del 2009 hasta igual mes del 2012. A los afectados se le realizó biopsia para conocer la presencia de coilocitos que producían alteraciones epiteliales y del corion en el tejido lesionado, así como su localización topográfica. En la casuística prevalecieron el sexo masculino, la mucosa de carrillo como el sitio anatómico de mayor incidencia y la displasia epitelial como la más relevante. Asimismo, la pérdida de la relación núcleo-citoplasma y la hiperplasia de la capa basal fueron las alteraciones hísticas más frecuentes.

With the purpose of evaluating the results of the clinical and histopathological diagnosis of the human papilomavirus associated with oral leukoplakia, a descriptive and cross-sectional study was carried out in 75 patients with this condition, who were treated at the Stomatology Department of the Polyclinic of Specialties from "Saturnino Lora" Provincial Teaching Clinical Surgical Hospital of Santiago de Cuba, from September 2009 to the same month of 2012. Biopsies were taken from patients to detect the presence of koilocytes producing chorion and epithelial changes in damaged tissue, as well as their topographic location. Male sex, buccal mucosa as the anatomical site of highest incidence and epithelial dysplasia as the most significant prevailed in the case material. Likewise, the loss of the nuclear-cytoplasmic ratio and hyperplasia of the basal layer were the most frequent tissue alterations.

Infección por papilomavirus humano en pacientes con liquen plano bucal / Infection due to human papilomavirus in patients with oral lichen planus i: en

Se efectuó un estudio descriptivo y transversal de 85 pacientes con liquen plano bucal asociado al virus del papiloma humano, atendidos en la consulta estomatológica del Policlínico de Especialidades del Hospital Provincial Docente Clinicoquirúrgico "Saturnino Lora Torres" de Santiago de Cuba, desde noviembre del 2008 hasta igual mes del 2011, con vistas a evaluar los resultados del diagnóstico histopatológico de esta afección. Entre las variables analizadas figuraron: edad, sexo, diagnóstico clinicohistopatológico, localización anatómica, factores de riesgo, alteraciones celulares que aparecen en el epitelio y magnitud de la displasia epitelial. En la casuística predominaron ambos sexos, el grupo etario de 20-29 años, la mucosa de carrillo como el sitio de mayor incidencia, la presencia de coilocitos como el hallazgo histológico más significativo y elevadas proporciones de la displasia epitelial leve.

A descriptive and cross sectional study of 85 patients with oral lichen planus associated with the virus of human papiloma, assisted in the estomatological service from the Specialties Polyclinic in "Saturnino Lora Torres" Teaching Clinical-Surgical Provincial Hospital from Santiago de Cuba was carried out from November, 2008 to the same month of 2011, with the aim of evaluating the results of the histological and pathological diagnosis of this disorder. Among the analyzed variables there were: age, sex, clinical histological and pathological diagnosis, anatomical localization, risk factors, cellular changes which appear in the epithelium and magnitude of the epithelial dysplasia. The age group 20-29, both sexes, the cheek mucosa as the place of greater incidence, the koilocytos presence as the most significant histological finding, high proportions of the mild epithelial dysplasia prevailed in the case material.

Detección del virus papiloma humano: influencia del tipo de muestra y la severidad de la lesión intraepitelial cervical / Detection of human papillomavirus: the influence os sample type and severity od cervical intraepithelial lesion

Identificar la influencia del tipo de muestra y la severidad de la lesión, en la detección del ácido desoxirribonucleico del virus papiloma humano mediante reacción en cadena de polimerasa. Entre octubre 2008 y enero 2009, se seleccionaron 68 pacientes con diagnóstico histológico de lesión intraepitelial. Se realizó la detección del ácido desoxirribonucleico de virus papiloma humano a través de reacción en cadena de polimerasa, en muestra citológica e histológica de cuello uterino. Se analizaron los resultados agrupados según tipo de muestra (citológica o histológica) y tipo de lesión intraepitelial (alto o bajo grado). Servicio de Ginecología de la Maternidad "Concepción Palacios" La sensibilidad de la reacción en cadena de polimerasa para la detección del ácido desoxirribonucleico del virus papiloma humano en muestra histológica fue 92,98 por ciento, mayor que la citológica 72,06 por ciento (P < 0,05). La severidad de la lesión no afectó la capacidad global de detección de la prueba (P > 0,05). En lesiones de bajo grado la sensibilidad del extendido fue de 65 por ciento y la de la biopsia fue de 97,2 por ciento; mientras que en las lesiones de alto grado fue de 82,14 por ciento (extendidos) y 85,71 por ciento (biopsias). La severidad de la lesión intraepitelial (alto o bajo grado) no afecta la eficacia de la prueba para detectar el ácido desoxirribonucleico del virus papiloma humano. La detección fue más efectiva en muestras histológicas que en citológicas

Identify the influence of the kind of sample and the severity of the injury, to detect the desoxyribonucleic acid of the human papilloma virus using polymerase chain reaction. Between October 2008 and January 2009, 68 patients with histological diagnosis of intraepithelial lesion were selected, making detection of human papilloma virus desoxyribonucleic acid in polymerase chain reaction, in both, histological and cytological cervical sample. Analysed the results grouped by type specimen (cytological and/or histological) and type of lesion (high or low grade). Service of Gynecology of the Maternidad "Concepcion Palacios", The sensitivity of the polymerase chain reaction for the detection of human papilloma virus desoxyribonucleic acid in histological sample was 92.98 percent, higher than the cytological 72.06 percent (P < 0.05). The severity of the lesions didn’t afect the detection capability of polymerase chain reaction. (P>0.05). The sensitivity of the extended in low grade lesions was 65 percent and the biopsy was 97.2 percent; while in high-grade lesions was 82.14 percent (extended) and 85.71 percent (biopsies). The severity of intraepithelial lesion (high or low grade) does not affect the effectiveness to detect human papilloma virus desoxyribonucleic acid. Detection was more effective in histological samples than in cytological

Tipos de papilomavirus humanos más frecuentes en muestras cubanas de cáncer cervical / The more frequent types of human papillomavirus in Cuban samples of cervix cancer

El cáncer del cuello uterino (CCU) es considerada una enfermedad de transmisión sexual, debido a los factores involucrados en su aparición y desarrollo, se reconoce a la infección por el papilomavirus humano (VPH) como el principal agente etiológico de esta enfermedad. En Cuba este tumor ocupa el 2do lugar en incidencia y el 4to en mortalidad entre las enfermedades malignas que afectan al sexo femenino. El presente estudio persigue como objetivos determinar los tipos de VPH presentes en muestras de tumores de cáncer de cérvix en mujeres cubanas, así como describir el comportamiento de diferentes factores de riesgo asociados a esta enfermedad. Se analizaron 45 muestras de cáncer cérvico uterino y se determinó la presencia de 20 tipos de VPH mediante el uso de la reacción en cadena de la polimerasa con cebadores específicos, se encontró en ellas un 91,1 por ciento de positividad. El genotipo 16 fue el más prevalente, seguido por el 18, 45, 31, 39, 51, 56, 59, PAP238A. No se encontraron en ninguna de las muestras los tipos de bajo riesgo 6 y 11. La promiscuidad mostró ser el factor de mayor interés en nuestro estudio. El conocimiento de los tipos virales presentes en los tumores del cérvix uterino en nuestras pacientes es importante a la hora de plantearse el desarrollo y uso de vacunas tanto profilácticas como terapéuticas

Cervix cancer (UCC) is considered a sexually transmitted disease due to factors involved in its appearance and development and this infection is recognized as the main etiological agent of this entity. In Cuba this type of tumor is placed in 2nd category in incidence and in 4th place in mortality among the malignant disease affecting the female sex. The objective of present study is to determine the types of human virus papiloma (HVP) present in samples of cervix tumors in Cuban women, as well as to describe the behavior of different risk factors associated with this disease. Forty five samples of cervix cancer were analyzed and the presence of 20 types of HVP was determined by polymerase chain reaction with specific primers founding in them a 91,1 percent of positivity. Genotype 16 was the more prevalent, followed by the 18, 45, 31, 39, 51, 56, 59, PAP23A. The low risk type 6 and 11 weren't founded in samples. Promiscuity was the more interesting risk factor in our study. Knowledge of the viral types present in cervix cancer in our patients is very important when we approach the development and the use of prophylactic and therapeutical vaccines

Predictive Value of Detection of hTERC Gene Copy Number in Cervical Epithelial Cells by means of Fluorescence in situ Hybridization and Human Papilloma Virus Testing for Cervical Intraepithelial Neoplasia / 中华医院感染学杂志

OBJECTIVE To explore the predictive value of human telomerase RNA gene component(hTERC) gene amplification and high-risk human papilomavirus(HR-HPV) testing in cervical intraepithelial neoplasia(CIN) as a marker for early diagnosis of cervix carcinoma.METHODS Fluorescence in situ hybridization(FISH) was used to detect the amplification of hTERC of cervical epithelial cells in 72 cases.By using hybrid capture 2(HC-2),two types of the HR-HPV DNA(HPV16/18) of each case were detected.Then,the results were compared with the pathologic diagnosis.The dual-color probe we used was GLP TERC/CSP 3.HeLa cells and lymphocytes from normal marrow were the positive control,while the cervical specimens from healthy outpatients were the negative control.RESULTS hTERC Gene amplification of specimens was tested in 72 cases,the positive amplification rate of hTERC gene in the cervicitis/CINⅠgroup and normal,compared to the cervical carcinomas(100%) and CIN Ⅱ/Ⅲ(68.75%),which showed a significant difference.The rates in CINⅡ and CINⅢ were 60.00% and 83.33%,respectively,which showed a significant difference compared with normal and CINⅠ/inflammation groups.hTERC gene amplification was positive in both HeLa cells and lymphocytes from normal marrow and HC-2 testing was positive in 32 cases of patients containing 11 cases of CINⅡ/Ⅲ,3 cases of cervical cancer,18 cases of cervicitis/CIN1 diagnosed.The positive predictive value(PPV) and specificity(Sp) of hTERC for the high-grade CIN was significantly higher than the PPV and Sp of HC-2 HR-HPV testing.CONCLUSIONS hTERC Gene involves in the progression and occurrence of cervical intraepithelial neoplasia and cervical squamous carcinoma.As a marker for early diagnosis of cervical intraepithelial neoplasia and cervical squamous carcinoma,the FISH method for hTERC gene is more reliable to differentiate the malignant diseases from the benign ones in cervixes than HC-2 HR-HPV DNA testing.The combined detection of HR-HPV and hTERC gene will provide more effective and suitable management to enhance the early diagnosis rate of cervical intraepithelial neoplasia and cervical squamous carcinoma.

Aspectos estruturais da família de uma gestante com Papilomavírus humano / Structural aspects of the family of a pregnant woman with human Papillomavirus

Introdução: família pode ter muitas atribuições, como a consanguinidade, o parentesco e a afi nidade através do casamento. Vários fatores influenciam na sua estrutura, gerando crises, incluindo-se fatores sociopolíticos e econômicos, religiosos e culturais, tais como a violência, o desemprego, as doenças, dentre outros. Objetivo: avaliar aspectos estruturais de uma família com portadora do papilomavírus humano (HPV) assistida em um serviço de saúde, com base no modelo Calgary. Métodos: estudo do tipo exploratório-descritivo, com abordagem qualitativa, sendo utilizado como referencial teórico o Modelo Calgary de Avaliação de Famílias. O sujeito da pesquisa foi uma mulher gestante e portadora de lesão por HPV, acompanhada em um Centro de Atenção Secundária na abordagem às doenças sexualmente transmissíveis (DST) do município de Fortaleza - CE. A coleta de dados foi realizada em janeiro de 2007 através de entrevistas, utilizando como instrumento um roteiro semiestruturado. As falas foram transcritas com consequente realização de discussões e analisadas com embasamento na literatura pertinente, apresentadas através de genograma, ecomapa e depoimentos da família. Resultados: percebemos, nesse estudo, que a doença não interferiu na relação conjugal, nem afetou o desenvolvimento da família nuclear (o casal); que a gestante apresenta um forte vínculo com sua família extensa e que a família nuclear é um sistema familiar fechado, com pouca interaçãosocial. Conclusão: apesar de o casal relatar que não houve grandes repercussões com a descoberta do HPV, emergiram os sentimentos de vergonha e medo de rejeição, comprovando a existência de estigmas associados às DST.

Introduction: family can have many defi nitions as the consanguinity, the kinship and the affi nity through marriage. Several factors infl uence its structure causing crisis, which include socio-political and economical, religious and cultural factors, such as violence, unemployment, diseases etc. Objective: to evaluate structural aspects of one family with carrier of Human Papilomavirus (HPV) assisted in a health service, based on the Calgary Model. Methods: descriptive exploratory study, with qualitative approach, using Calgary Model of family evaluation as theoretical reference. The subject of the research was a pregnant woman who had a lesion by HPV, assisted in a Centre of Secondary Attention in the approach to Sexually Transmitted Diseases (STD) from Fortaleza -CE. The data collection occured in January, 2007, through interviews and the instrument used was a semi-structured schedule. The speeches were transcribed with consequent execution of discussions and analyzed based on the pertinent literature, and presented through Genogram, Ecomap and family testimony. Results: in this study, we noticed that the disease did not interfere in the matrimonial relationship and in thedevelopment of the nuclear family (the couple); the pregnant presents a strong link with her extended family and the nuclear family has a closed family system, with little social interaction. Conclusion: Although the couple relates that there were no great repercussions with the discovery of HPV, the feeling of embarrassment, and fear of being rejected emerged, which confirm the existence of stigmas associated to STD.

THE HUMORAL AND CELLULAR IMMUNE RESPONSES INDUCED BY HPV18L1-E6/E7 DNA VACCINES IN MICE / 药物分析学报

Objective To construct eukaryotic expression vector of HPV18 L1- E6, E7 chimeric gene and examine the humoral and cellular immune responses induced by this DNA vaccines in mice. Methods The C-terminal of major capsid protein L1 gene and mutant zinc finger domains of early E6/7 oncogenes in HPV18 were integrated and inserted into eukaryotic expression vector pVAX1 to generate vaccines pVAX1-L1E6Mxx, E7Mxx. CHO cells were transiently transfected with the individual construct. Target protein expressions in the lysate of the transfected cells were measured by ELISA and immunocytochemistry. After BALB/c mice were vaccinated with various recombinant plasmids(pVAX1-L1-E6M3 or pVAX1-L1-E7M3) and immunie adjuvants (pLXHDmB7-2 or LTB) through different administration routes (intramuscular or intranasal) , the great cellular immune responses were produced as revealed by delayed-type hypersensitivity (DTH) and lymphocyte proliferation, and the expression of IL-4 and IFN- γ cells in CD4+ and CD8+subpopulations. Results The highly efficient expression of pVAX1-L1E6Mxx, E7Mxx vector in host eukaryotic cells were demonstrated both by ELISA and immunocytochemistry. The level of specific serum IgG against HPV in experiment groups mice was much higher than that of control group, and intranuscular immunization group had the highest antibody level. Intramuscular immunization groups were superior to intranasal immunization groups in DTH response, splenocyte proliferation and CD8+ IFN-γ + cells number, but CD4+ IL4+ cell number was higher in intranasal immunization groups. The immunization groups using pLXHDmB7-2 as adjuvant were superior to other groups in immunoresponse. Conclusion These DNA vaccines produce remarkable cellular and humoral immuneresponses in the mouse and may provide as prophylatic and therapeutic candidates for HPV induced cancer treatment.

Papiloma virus humano y neoplasia cervical: relación histopatológica. Hospital Regional Teodoro Maldonado Carbo, 1999-2000 / Human papilomavirus and cervical neoplasia: histopathologic relationship. Teodoro Maldonado Carbo Regional Hospital 1999-2000

Se realizó un estudio de tipo analítico, transversal de caracter retrospectivo, no aleatorio, monocéntrico, en el hospital Teodoro Maldonado Carbo; cuyo objetivo principal fue demostrar el grado de asociación de la infección por Papiloma virus humano y neoplasia cervical en pacientes que acudieron al hospital durante los años 1999 y 2000. El resultado principal fue la demostración de la relación entre la infección por Papiloma virus humano y la neoplasia cervical, siendo la población urbana más afectada y su mayor incidencia en la cuarta década de la vida.Conclusiones: se demostró por medio del trabajo la alta asociación de la enfermedad en relación a la infección, siendo el riesgo relativo de 3.9, y la ocurrencia relativa de 5.8.

We realized an analytic, transversal, retrospective study character in the Teodoro Maldonado Carbo Hospital whose primary target was to demonstrate the degree of association of the infection by human papillomavirus and cervical neoplasia in patients who went to the hospital during years 1999 and 2000.The main result was demonstration of the relation between the infection by human papillomavirus and cervical neoplasia, being the urban population affected and its greater incidence in fourth decade of life.Conclusions: we show that there exists a high association of the infection with relation to the disease, being 3.96 the relative risk of the relative occurrence of 5.8.

Inactivation of p73 Protein by Cervical Cancer-inducing HPV E6 Protein Novel p53-independent function of E6 / 대한산부인과학회잡지

OBJECTIVE: Human papillomavirus (HPV) is strongly implicated as a causative agent in the etiology of cervical cancer. Of its gene products, E6 and E7 oncoproteins play major roles by inactivation of cellular p53 and pRb tumor suppressor proteins, respectively. However, it has been recently suggested that p53 and/or pRb-independent functions of E6 and E7 are involved in cervical carcinogenesis. The purpose of this study is to identify novel a cellular target, p73, of E6 and to determine how E6 inactivates p73 function, METHODS: The interaction between E6 and p73 were identified by the yeast two-hybrid assay in vivo and the GST pull-down assay in vitro. The function of the interaction was determined by transient transfections using p21 promoter-CAT reporter plasmid. The molecular mechanism underlying the functional significance of the interaction was further assessed by in vivo and in vitro protein degradation assays, and gel mobility shift assays. RESULTS: Yeast two-hybrid and GST pull-down assays indicate a physical interaction between p73 and either HPV-16 or HPV-11 E6 proteins in vivo and in vitro, respectively. Transactivation domain (amino acid residues 1-49) is found to be absolutely required for this interaction. Transient co-expression of E6 significantly inhibits the p73-mediated activation of p21WAF1 promoter in a p53-defective C33A cell line. Using Ga14-p73 fusion protein, we demonstrate that E6 inhibition of p73 transactivation function is independent of sequence-specific DNA binding, which is confirmed by direct electrophoretic mobility shift assay. Moreover, E6 inhibits p73 function by interfering with the activity of the amino-terminal activation domain. The protein degradation assays in vivo and in vitro indicate that p73, unlike p53, is not susceptible to E6-dependent proteolysis. CONCLUSION: Throughout this study, we identified p73 as a novel cellular target of HPV-E6 protein and found that E6 binds p73 through the amino-terminal transactivation domain, and inhibits its transactivation function independent of the protein degradation and DNA binding. These overall results, consequently, suggest that in addition to the inactivation of p53, the functional interference of p73 by HPV-E6 may, at least in part, contribute to E6-mediated cellular transformation.