HPV vaccination programs in LMIC: is it time to optimize schedules and recommendations?

Abstract Objectives: Prophylactic HPV vaccines are a fundamental tool to reduce infections and tumors caused by the most prevalent types of these viruses, as this review points out. Several countries have adopted immunization programs that recommend vaccination against HPV for girls and adolescents between 9 and 14 years of age and, in some of them, also for boys. The programs also contemplate the immunization of adults, particularly in the case of individuals with different immunodeficiencies. Sources of data: The available vaccines are recommended for the prevention of tumors of the uterine cervix, vulva, vagina, penis, and anal canal. Moreover, two of the vaccines prevent the occurrence of genital warts, having been recently indicated for the prevention of oropharyngeal cancer. Data synthesis: Based on the evidence that antibody responses in girls were non-inferior after two doses when compared to three doses, several countries have decided to reduce the vaccination schedule for girls and boys up to 14 years of age from three to two doses, with an interval of six months between them. Recently, knowledge has been accumulating about the immunogenicity, duration of protection, and efficacy of a single-dose HPV vaccine regimen in girls and young women. Conclusion: Single-dose HPV vaccination could substantially reduce the incidence of pre-cancer and cervical cancer attributable to HPV, with reduced costs for vaccine delivery and simplified implementation, allowing more countries to introduce HPV vaccination or increase the adherence of the target population.

Perianal fistulizing Crohn's disease is associated with a higher prevalence of HPV in the anorectal fistula tract. A comparative study

Abstract Background & Aims Perianal fistulizing Crohn's disease is the main risk factor for anal cancer in patients with inflammatory bowel disease. Whether this occurs due to a higher frequency of human papillomavirus remains unclear. The authors aimed to evaluate the prevalence of HPV and high-risk HPV in patients with perianal Crohn's disease, compared with a control group. Methods The authors conducted a two-center cross-sectional study in which perianal fistulizing Crohn's disease patients were matched for age and sex with patients with anorectal fistula without Crohn's disease. Biopsy specimens were obtained from fistulous tracts during examination under anesthesia for both groups. The samples were sent for HPV detection and genotyping using the INNO-LiPA test. Results A total of 108 subjects (54 in each group) were recruited. The perianal fistulizing Crohn's disease group showed a statistically higher frequency of HPV in the fistulous tract than the control group (33.3% vs. 16.7%; p = 0.046). Separate analyses on high-risk types demonstrated that there was a numerically higher frequency of HPV in the perianal fistulizing Crohn's disease group. In multiple logistic regression, patients with perianal fistulizing Crohn's disease were found to have a chance of HPV 3.29 times higher than patients without Crohn's disease (OR = 3.29; 95% CI 1.20‒9.01), regardless of other variables. The types most frequently identified in the perianal fistulizing Crohn's disease group were HPV 11 (12.96%) and HPV 16 (9.26%). Conclusion Perianal fistulizing Crohn's disease is associated with a higher prevalence of HPV than in patients with anorectal fistula without Crohn's disease.

Improvement in dietary intake estimates through the combined use of different approaches / Melhora das estimativas de ingestão dietética pela utilização conjunta de duas abordagens

ABSTRACT Objective This study aimed to compare dietary intake estimates using two different methodological approaches: use of new portions obtained with the 24-Hour Diet Recall, which was applied in the current study population, and the application of calibration equations, which were estimated using the same 24h-recalls. Methods Calibration equations were estimated using linear regression. The medians and confidence intervals of energy and nutrient intakes were assessed using all the approaches. The U Mann Whitney test was applied to verify differences among dietary intakes obtained with the 24 Hour Recall and Food Frequency Questionnaire-based methods. The correlation between different measures was assessed with Spearman coefficient. Weighted Kappa was used to verify the capability of the Food Frequency Questionnaire -based methods to classify individuals in the same intake levels of the 24 Hour Recall. Results Nine of the eleven components that were analyzed using the Food Frequency Questionnaire with standard portions and calibrated had medians significantly different from those obtained using the 24 Hour Recall; only the measurements of vitamin E and energy were statistically equal. For the Food Frequency Questionnaire with 24 Hour Recall portions, only the medians of vitamin D and B12 did not significantly differ from the 24 Hour Recall medians. Finally, for the Food Frequency Questionnaire with 24 Hour Recall portions and calibrated, all components, except folate and iron, had medians statistically equal to those obtained using the 24 Hour Recall. Spearman correlation coefficients were higher for the Food Frequency Questionnaire with 24 Hour Recall portions calibrated for all the assessed components, and the values ranged from 0.27 (total fat) to 0.57 (iron). Higher Kappa correlation coefficients were found for the Food Frequency Questionnaire 24 Hour Recall portions calibrated. Conclusion Calibrated FFQ with portions estimated from the own target population obtained better estimates of dietary intake, with values considerably more similar to those obtained with the reference method.

RESUMO Objetivo Comparar estimativas de ingestão alimentar de Questionário de Frequência Alimentar em conjunto a duas abordagens: porções obtidas de Recordatórios-24h aplicados na população de estudo, e equações de calibração, calculadas a partir dos mesmos Recordatórios-24h. Métodos Foram descritas medianas e intervalos de confiança de energia e nutrientes. O teste U de Mann-Whitney foi aplicado para verificar diferenças entre os dados obtidos com o Recordatório-24h e com o Questionário de Frequência Alimentar. A correlação entre as medianas de ingestão foi verificada com o coeficiente de correlação de Spearman; e para verificar se os métodos baseados no Questionário de Frequência Alimentar foram capazes de classificar os indivíduos nos mesmos níveis de ingestão do Recordatório-24h, foi utilizado o coeficiente de Kappa ponderado. Resultados Para o Questionário de Frequência Alimentar Porção Padrão calibrado, 9 dos 11 nutrientes analisados tiveram medianas diferentes das do Recordatório-24h. Para o Questionário de Frequência Alimentar Porção do Recordatório-24h, somente as vitaminas D e B12 não apresentaram diferença significativa em relação ao Recordatório-24h; para o Questionário de Frequência Alimentar Porção do Recordatório-24h calibrado, todos os nutrientes, à exceção de folato e ferro, tiveram medianas estatisticamente iguais às obtidas com o Recordatório-24h. Os coeficientes de correlação de Spearman foram maiores para o Questionário de Frequência Alimentar Porção do Recordatório-24h calibrado para todos os nutrientes avaliados, variando de 0,27 (gordura total) a 0,57 (ferro). Em relação ao Kappa ponderado, os maiores coeficientes foram encontrados para o Questionário de Frequência Alimentar Porção do Recordatório-24h calibrado. Conclusão A utilização do Questionário de Frequência Alimentar calibrado e com porções estimadas na própria população de estudo apresenta melhores estimativas da ingestão alimentar, com valores mais próximos ao método de referência.

Juvenile-onset recurrent respiratory papillomatosis with pulmonary involvement and carcinomatous transformation

Papilloma associated with recurrent respiratory papillomatosis (RRP), caused by human papilloma virus (HPV) infection types 6 and 11, is the most common benign neoplasm of the larynx. The clinical features of RRP vary widely from mild to aggressive forms. RRP in children is known as juvenile-onset recurrent respiratory papillomatosis (JORRP). Its outcome may be poor or even fatal due to the high rate of recurrence and eventual spread to the entire respiratory tract. Pulmonary invasion is reported to occur in 3.3% of patients with RRP, and malignant transformation in 0.5% of patients. We report the case of a 39-year-old female patient with a diagnosis of JORRP from the age of 3 years, with extensive bilateral pulmonary involvement and malignant transformation. Analysis of the papilloma and carcinomatous tissues revealed the presence of HPV type 11, which is associated with rapid and aggressive progression. We discussed the case on the basis of a literature review on pulmonary invasion, malignant transformation, and HPV 11 aggressiveness.

Innate immunity and HPV: friends or foes

Most human papillomavirus infections are readily cleared by the host immune response. However, in some individuals, human papillomavirus can establish a persistent infection. The persistence of high-risk human papillomavirus infection is the major risk factor for cervical cancer development. These viruses have developed mechanisms to evade the host immune system, which is an important step in persistence and, ultimately, in tumor development. Several cell types, receptors, transcription factors and inflammatory mediators involved in the antiviral immune response are viral targets and contribute to tumorigenesis. These targets include antigen-presenting cells, macrophages, natural killer cells, Toll-like receptors, nuclear factor kappa B and several cytokines and chemokines, such as interleukins, interferon and tumor necrosis factor. In the present review, we address both the main innate immune response mechanisms involved in HPV infection clearance and the viral strategies that promote viral persistence and may contribute to cancer development. Finally, we discuss the possibility of exploiting this knowledge to develop effective therapeutic strategies.

HPV-related external genital lesions among men residing in Brazil

Abstract The aims of this study were to determine the incidence of external genital lesions (EGLs), specifically histologically confirmed condyloma (genital warts) and Penile Intraepithelial Neoplasia (PeIN), and genital HPV infection progression to EGLs among healthy men aged 18-73 residing in Brazil. Subjects included 1118 men enrolled in the HPV Infection in Men (HIM) study between July 2005 and June 2009. At each visit, EGLs were biopsied and subjected to pathological evaluation. HPV status in genital swabs and biopsies was determined by Linear Array and INNO-LiPA, respectively. Age-specific EGLs incidence and the proportion and median time to EGL development were estimated. Kaplan-Meier cumulative incidence rates at 6, 12, and 24 months were determined. During follow-up, 73 men developed an incident EGL. Men could develop multiple EGLs and there were 36 men with condyloma, 27 men with lesions suggestive of condyloma, six men with PeIN, and 20 men with non-HPV lesions. HPV-positive men who developed EGLs were younger (p = 0.002) than men that did not develop lesions. Among the 815 men with HPV infection, 4% progressed to EGL with the same HPV detected in the swab. During follow up, 15.7% of genital HPV-6 and HPV-11 infections progressed to condyloma (median progression time of nine months for HPV-6 versus 6.8 months for HPV-11). Approximately 1% of HPV-16 infections progressed to PeIN with a median progression time of 25 months. HPV types covered by the 4-valent HPV vaccine were detected in 82.3% and 83.3% of condyloma and PeIN, respectively. The high burden of HPV and high frequency of progression to disease underscores the need to offer HPV prophylactic vaccination to men to reduce the overall burden of infection and diseases caused by HPV.

Human Papillomavirus and students in Brazil: an assessment of knowledge of a common infection - preliminary report / HPV e estudantes no Brasil: avaliação do conhecimento de uma infecção comum-relato preliminar

Abstract Introduction: Human Papillomavirus (HPV) infection is the most prevalent sexually transmitted disease worldwide. One of the barriers to the implementation of prevention programs against the disease is the limited knowledge possessed by most populations regarding the virus and its possible consequences. Objective: The purpose of this study was to evaluate the knowledge of Brazilian college students on transmission, clinical manifestations, and diseases correlated with HPV, highlighting the poor knowledge of a very common infection. Methods: A total of 194 students answered a questionnaire about transmission, clinical features and the possible consequences of persistent HPV infection. The questionnaire was self-applied under the supervision of the authors. Results: The clinical manifestations of HPV infection were not clear to most students. Incorrect assumptions of the clinical manifestations of HPV infection included: bleeding (25%), pain (37%) and rashes (22%). Twelve per cent of respondents did not recognize warts as an HPV-related disease. Regarding potential consequences of persistent infection, students did not recognize a relationship between HPV and laryngeal carcinoma (80.9%), pharyngeal carcinoma (78.9%), anal carcinoma (73.2%), vulvar carcinoma (65.4%) and vaginal carcinoma (54.6%). Large portions of the population evaluated were unaware of modes of HPV transmission beyond genital contact. Conclusion: Knowledge of HPV by the population evaluated in this study is partial and fragmented. Lack of knowledge may contribute to the further spread of the disease. Public health policies for education and guidance of the population should be implemented in Brazil.

Resumo Introdução: A infecção pelo papilomavírus humano (HPV) é a doença sexualmente transmissível mais prevalente em todo o mundo. Uma das barreiras para a implantação de programas de prevenção contra a doença é o conhecimento limitado da maioria das populações sobre o vírus e suas possíveis consequências. Objetivo: Avaliar o conhecimento dos estudantes universitários brasileiros sobre a transmissão, as manifestações clínicas e as doenças correlacionadas com o HPV, com destaque para o pouco conhecimento de uma infecção muito comum. Método: Responderam a um questionário sobre a transmissão, características clínicas e as possíveis consequências da infecção persistente pelo HPV 194 estudantes. O questionário foi autoaplicado, sob a supervisão dos autores. Resultados: As manifestações clínicas da infecção pelo HPV não eram claras para a maioria dos estudantes. As suposições incorretas das manifestações clínicas da infecção pelo HPV incluíam: hemorragia (25%), dor (37%) e erupções cutâneas (22%) -12% dos entrevistados não reconheciam as verrugas como uma doença relacionada ao HPV. Quanto às potenciais consequências da infecção persistente, os alunos não reconheciam uma relação entre HPV e câncer de laringe (80,9%), carcinoma da faringe (78,9%), carcinoma anal (73,2%), carcinoma vulvar (65,4%) e carcinoma vaginal (54,6%). Grandes porções da população avaliada desconheciam os modos de transmissão do HPV além do contato genital. Conclusão: O conhecimento de HPV pela população avaliada neste estudo é parcial e fragmentado. A falta de conhecimento pode contribuir para a propagação da doença. Políticas públicas de saúde para a educação e orientação da população devem ser implantadas no Brasil.

Prevalence of human papillomavirus infection in squamous cell carcinoma of the anal canal in a Northeast City in Brazil: viral genotyping and clinical aspects

Background: Anal cancer malignancies comprise about 1.5 to 3% of cancers from the gastrointestinal in which high-risk types of human papillomavirus (HR-HPV) is responsible for >80% of cases. The aim of this work was to detect and perform human papillomavirus (HPV) genotyping in squamous cell carcinoma specimens from the anal canal and to investigate the association between viral infection and histopathological and clinical aspects. Methods: The presence of genotype-specific HPV DNA in formalin-fixed paraffin embedded tissue from 27 anal SCC samples from a reference cancer hospital of São Luís, State of Maranhão, Brazil was performed by Linear Array HPV Genotyping Test and the INNO-LiPA HPV Genotyping Assay. Fisher's Exact test and Chi-square test were performed in order to evaluate the association between HPV type and clinical and morphological variables. P values less than 0.05 were considered statistically significant. Results: Average age of patients at the time of diagnosis was 54.96 years ± 15.81; 74.07% of patients were female. Vegetative ulcers represented the most common type of lesion (22.22%). The lesions ranged in size from 2.1 cm to 5.0 cm and mostly were well-differentiated (70.38%). Lymph node involvement was observed in 26% of the patients. Molecular evaluation revealed that HPV infection was detected in 81.48% of the lesions, and the most common type found was the oncogenic HPV 16. Statistical analysis indicated that the clinical and histopathological variables were not associated with HPV infection. Conclusions: Our results indicate that anal SCC rarely occurs in the absence of HPV and emphasize the predominant role of HPV16. The evaluation about genotype-specific prevalence of HPV in anal SCC is important to assess the potential benefit of HPV vaccination (AU)

Association between human Papillomavirus and colorectal adenocarcinoma and its influence on tumor staging and degree of cell differentiation / Associação do Papilomavírus humano com o adenocarcinoma colorretal e sua influência no estadio tumoral e no grau de diferenciação celular

BACKGROUND: Colorectal cancer is one of the most common types of neoplasia among the worldwide adult population. Among neoplasms of the gastrointestinal tract, it is ranked second in relation to prevalence and mortality, but its etiology is only known in around 5% of the cases. It is believed that 15% of malignant diseases are related to viral oncogenesis. AIM: To correlate the presence of HPV with the staging and degree of cell differentiation among patients with colorectal adenocarcinoma. METHODS: A retrospective case-control study was conducted on 144 patients divided between a test group of 79 cases of colorectal cancer and a control group to analyze 144 patients aged 25 to 85 years (mean, 57.85 years; standard deviation, 15.27 years and median, 58 years). Eighty-six patients (59.7%) were male. For both groups, tissue samples from paraffin blocks were subjected to DNA extraction followed by the polymerase chain reaction using generic and specific primers for HPV 16 and 18. Dot blot hybridization was also performed with the aim of identifying HPV DNA. RESULTS: The groups were shown to be homogenous regarding sex, age and site of HPV findings in the samples analyzed. Out of the 41 patients with HPV, 36 (45.6%) were in the cases and five (7.7%) were in the control group (p<0.001). All the HPV cases observed comprised HPV 16, and HPV 18 was not shown in any of the cases studied. There were no significant differences in comparisons of sex, age and site regarding the presence of HPV in either of the groups. It was not observe any significant difference in relation to staging or degree of cell differentiation among the patients with colorectal cancer. CONCLUSION: Human papillomavirus type 16 is present in individuals with colorectal carcinoma. However, its presence was unrelated to staging or degree of differentiation. .

RACIONAL: O câncer colorretal é uma das neoplasias mais frequentes entre a população adulta mundial, e entre as do trato gastrointestinal, é a segunda em relação à prevalência e mortalidade sendo a sua causa conhecida apenas em cerca de 5% dos casos. Acredita-se que 15% das doenças malignas estariam relacionadas à oncogênese viral. OBJETIVO: Correlacionar a presença do HPV com o estadiamento e o grau de diferenciação celular dos pacientes portadores de adenocarcinoma colorretal. MÉTODOS: Foi realizado um estudo retrospectivo do tipo caso-controle com 144 pacientes divididos em um grupo teste representado por pacientes com câncer colorretal em um total de 79 casos e um grupo controle correspondente à pacientes com doença benigna totalizando 65 casos. Após a aplicação dos critérios de exclusão, foi possível analisar 144 pacientes com idade entre 25 a 85 anos (média de 57,85 anos com desvio-padrão de 15,27 anos e mediana de 58 anos). Oitenta e seis (59,7%) pacientes eram homens. Amostras teciduais a partir de blocos de parafina de ambos os grupos foram submetidos à extração do DNA e em seguida foi realizada reação em cadeia da polimerase com iniciadores genéricos e específicos para HPV 16 e 18 e também a hibridização do tipo dot blot com o intuito de identificar o DNA do HPV. RESULTADOS: Os grupos se mostraram homogêneos quanto a sexo, idade e localização do HPV nas amostras analisadas. Dos 41 pacientes com HPV, 36 (45,6%) eram do grupo teste e cinco (7,7%) do grupo controle (p<0,001). Todos os casos de HPV observados correspondiam ao HPV 16 não sendo evidenciado HPV 18 em nenhum caso estudado. Não houve diferença significativa na comparação realizada quando se considerou o sexo, idade e localização ...

Determinacao da prevalencia de HPV em amostras de mucosa oral/orofaringea em um distrito rural de Sao Paulo / Determination of HPV prevalence in oral/oropharyngeal mucosa samples in a rural district of Sao Paulo

OBJETIVO: Averiguar a eficácia da metodologia para coleta de amostras em cavidade oral e orofaringe e determinar a prevalência do HPV na cavidade oral e orofaringe de adultos e crianças. MÉTODO: A população estudada foi atendida por um programa assistencial em um distrito rural de São Paulo. Os indivíduos foram convidados a doar amostras independentemente de queixas. RESULTADOS E CONCLUSÃO: Foram incluídos no estudo 47 homens, 77 mulheres e 22 crianças, dos quais amostras da cavidade oral foram obtidas por bochecho e gargarejo com antisséptico oral comercial. Foram encontrados três resultados positivos (2,4%) em adultos, duas amostras de HPV 55 e uma amostra de HPV 58. Não foram observados resultados positivos em crianças. Além disso, concluímos que o método de coleta com o enxágue bucal com antisséptico mostrou-se eficaz e rápido para a detecção de HPV na cavidade oral e orofaríngea na população geral. .

Knowledge about HPV infection in the oral cavity/oropharynx may contribute to the elucidation of the role it plays in Head and Neck Squamous Cell Carcinoma (HNSCC). OBJECTIVE: To determine the effectiveness of the methodology used for sampling the oral cavity and oropharynx mucosae and to determine the prevalence of HPV in the oral cavity and oropharynx of adults and children. METHOD: The study population was served by an assistance program in a rural district of São Paulo. The subjects were asked to donate samples regardless of complaints. RESULTS AND CONCLUSION: The study included 47 men, 77 women and 22 children, of which the oral cavity samples were obtained by gargling with commercially-available antiseptic mouthwash. We found 3 positive samples (2.4%) in adults: 2 HPV 55 and one HPV 58. No positive results were found in children. Furthermore we concluded that the sampling method with the mouthwash proved effective and fast for the detection of HPV in the oral cavity and oropharynx in the general population. .

Identificação do papilomavírus humano em doentes com carcinoma de células escamosas do canal anal e sua relação com o grau de diferenciação celular e estadiamento / Identification of human papillomavirus in patients with anal squamous cell carcinoma and its relation with the grade of cellular differentiation and staging

OBJETIVO: Identificar os tipos de papilomavírus humano (HPV) nos portadores de carcinoma do canal anal (CCA), relacionando-os ao grau de diferenciação celular e estadiamento da lesão, em pacientes do Belém, Pará, entre 1998 e 2000. MÉTODOS: Foi realizado um estudo de caso-controle com 75 pacientes, divididos em: Grupo Teste, com 33 portadores de carcinoma do canal anal, e o Grupo Controle, com 42 portadores de doenças não-neoplásicas do canal anal. Os tipos virais foram identificados por PCR e dot blot. O teste exato de Fischer foi utilizado para avaliar a ocorrência de HPV. Adotou-se a tabela de contingência 3x2 para representar a distribuição dos tipos de HPV. Nos testes de hipóteses, foi prefixado o nível de significância alfa=0,05 para a rejeição da hipótese de nulidade. RESULTADOS: A prevalência do HPV foi significante entre os Grupos Teste (60,6 por cento) e Controle (26,2 por cento) (p=0,0027). Os tipos virais mais comuns foram 16 (42,4 por cento) e 18 (15,2 por cento). Observaram-se diferenças entre grupos na prevalência do HPV 16 (p=0,027) e 18 (p=0,043) no Grupo Teste, e o tipos 16 (19,0 por cento,) e 18 em (2,4 por cento) no Grupo Controle. No Grupo Teste, avaliou-se a distribuição dos tipos de HPV em relação ao estadiamento e ao grau de diferenciação celular, não apresentando diferenças estatisticamente significativas. CONCLUSÃO: O carcinoma de células escamosas do canal anal está associado à presença de HPV, e os tipos 16 e 18 são os mais frequentes.

OBJECTIVE: To identify the most predominant types of human papillomavirus (HPV) in carriers of the anal canal carcinoma (ACC), relating them to the cell differentiation and lesion staging degree, in patients from Belém, Pará, Brazil, between 1998 and 2000. METHODS: A case-control study was conducted with 75 patients, divided into Test Group, with 33 carriers of the anal canal carcinoma, and Control Group, with 42 carriers of non-neoplastic diseases of the anal canal. The methods employed to identify the viral types were the polymerase chain reaction and the dot blot. The Fisher's exact test was used to assess the HPV occurrence. The distribution of HPV types was analyzed by 3x2 contingency tables, representing the distribution of HPV types. For hypothesis testing, the significance level alfa=0.05 was previously established for rejection of the null hypothesis. RESULTS: HPV was significantly prevalent (p=0.0027) in the Test (60.6 percent) and Control Groups (26.2 percent) (p=0.0027). The most prevalent viral types were HPV 16 (42.4 percent) and 18 (15.2 percent). Significant differences related to the prevalence of HPV 16 and 18 were verified between both groups (p=0.027 and p=0.043, respectively). In the Control Group, HPV 16 was found in 19.0 percent, whereas HPV 18 was observed in 2.4 percent. In the Test Group, we evaluated the distribution of HPV types according to the staging and degree of cell differentiation, and found no significant differences between the results of the different groups. CONCLUSION: Squamous cell carcinoma of the anal canal is associated with the HPV presence, and the 16 and 18 types are the most frequently found.

HPV vaccination: the beginning of the end of cervical cancer? - A Review

Human papillomavirus (HPV) is responsible for all cases of cervical cancer, as well as a great percentage of other anogenital tumors and oropharyngeal tumors. Since the main etiologic factor for these diseases is a virus, prophylactic measures are the best way to reduce the burden caused by the infection and associated disease. This review brings up to date information on the two commercially available prophylactic HPV vaccines against HPV, as well as presenting the ongoing research on HPV peptide, protein and dendritic cell based therapeutic vaccines.

Biomarcadores na triagem do câncer do colo uterino / Biomarkers in cervical cancer screening

A infecção persistente por papilomavírus humano (HPV) é o principal fator de risco para o câncer do colo uterino e de suas lesões precursoras.Programas de triagem que utilizam a citologia oncótica (exame de Papanicolaou) levaram a uma diminuição significativa na incidência deste tipo tumoral, apesar de suas limitações na detecção de atipias leves e adenocarcinomas. Em vista disso, a identificação de novos biomarcadores que permitam monitorar eventos moleculares associados à progressão tumoral em amostras histológicas ou citológicas, poderá melhorar a detecção de lesões com maior risco de progredirem. A simples detecção do DNA de HPV como principal parâmetro na triagem do câncer do colo uterino e de suas lesões precursoras é ainda um ponto controverso por ter um valor preditivo positivo baixo. Por outro lado, o desenvolvimento de tecnologias que detectem e quantifiquem os transcritos dos oncogenes virais E6 e E7, estão sendo consideradas para a avaliação precisa da atividade oncogênica viral associada à progressão tumoral. Além disso, análises detalhadas das interações das oncoproteínas de HPV e seus alvos celulares permitirão definir possíveis novos biomarcadores. Umdos principais exemplos é o aumento da expressão da proteína inibitória das quinases dependentes de ciclina p16ink4a promovida pelapresença de E7. Diversos estudos utilizam o aumento da expressão da proteína p16ink4a para identificar células displásicas em amostrashistológicas e esfregaços cervicais. Esta revisão foca algumas das principais linhas de pesquisa na identificação de biomarcadores e suapossível utilização na triagem do câncer cervical e de suas lesões precursoras.

Persistent infection with oncogenic human papillomavirus (HPV) is the main risk factor for cervical cancer and its precursor lesions. Cytologicalscreening programs using the Pap test have led to a substantial reduction in the incidence of cervical cancer despite its limitation in detecting minor atypias and adenocarcinomas. Therefore, the identifi cation of new biomarkers that allow the monitoring of molecular events associated to tumor progression in histological or citological specimens may improve the detection of lesions with higher risk of progression. HPV DNA detection as a primary screening parameter has been controversially discussed due to its very low predictive value. On the other hand, the development of new technologies for the determination of high risk HPV activity by detecting E6 and E7 transcripts has the potential to more accurately evaluate tumor progression. Moreover, the detailed analysis of HPV oncoproteins and cellular targets will allow the defi nition of new possible biomarkers. One of the best examples is the up-regulation of the cyclin dependent kinase inhibitor p16ink4a expression by E7. Several studies use p16ink4a overexpression to identify dysplastic cells in histological samples and cytological smears. This review focuses on biomarkers studies and their possible role in screening cervical cancer and precursor lesions.

Resultados do exame anátomo-patológico e "Polymerase Chain Reaction (PCR)" na forma clinica e subclinica da infecção anal pelo Papilomavirus Humano (HPV): estudo em quatro grupos de pacientes / Histopathological and PCR results for clinical and subclinical forms of HPV anal infection: study of four groups of patients

O Papilomavírus Humano tem alta incidência na população. O objetivo deste trabalho é o estudo dos resultados encontrados no exame anatomo-patológico e no PCR das formas clínica e subclínica da infecção anal por HPV em quatro grupos de pacientes. MÉTODO: Foram estudados 10 pacientes com prurido anal idiopático, seis com infecção genital pelo HPV, tratada, seis com condiloma anal tratado e oito com condiloma anal. As verrugas foram biopsiadas nos oito pacientes com condiloma e feito exame de anuscopia de alta resolução com biópsia dirigida nos outros 22 pacientes. O material foi encaminhado para exame anátomo-patológico e depois, a partir do mesmo bloco de parafina, foi feito o exame de PCR. Resultados: O anátomo-patológico foi positivo para HPV em todos os pacientes, sendo que nos oito com condiloma confirmou-se a forma clínica e em 22 diagnosticou-se a subclínica com 13 casos de neoplasia intraepitelial associada. O PCR foi positivo em 91,9 por cento dos 22 pacientes da forma subclínica ao anátomo-patológico e em 87,5 por cento dos oito pacientes da forma clínica. O tipo predominante nos casos de HPV anal subclínico foi o 16 e o predominante nas verrugas foi o 11. CONCLUSÕES: O exame anátomo-patológico foi positivo para HPV em todos os pacientes, propiciando também o diagnóstico de 13 casos de neoplasia intraepitelial, sendo dois de carcinoma "in situ". O PCR foi positivo em 91,9 por cento dos pacientes da forma subclínica ao anátomo-patológico e em 87,5 por cento da forma clínica ao anátomo-patológico. O tipo predominante da forma subclinica foi o 16 e das verrugas foi o 11.

The purpose of this study is to analyze the results found in the pathological examination and PCR test for clinical and subclinical HPV anal infections in four groups of patients. Methods: The four groups studied were: ten patients with idiopathic anal pruritus, six with treated HPV genital infection, six with treated anal condyloma, and eight with anal condyloma. Eight patients with condyloma underwent wart biopsy, and high-resolution anoscopy with directed biopsy was performed in the remaining 22 patients. Paraffin wax embedded biopsy specimens were sent to pathological analysis, and later PCR was carried out on the same samples. Results: Through the pathological examination, the presence of HPV is positive in all patients studied: clinically in the eight patients with condyloma, and subclinically in the others 22. Thirteen of these 22 patients presented and associated intraepithelial neoplasia. PCR was positive in 91,9 percent of the 22 patients those who presented the subclinical infection at pathology examination and 87,5 percent of the eight patients that presented the clinical infection the most common type of anal subclinical HPV infection was HPV-16 and HPV-11 when warts were presented. Conclusions: Pathological findings related to HPV were presented in all patients studied, and 13 cases were diagnosed two of them were carcinoma in situ. PCR was positive in 91,9 percent of patients presenting the subclinical infection, and in 87,5 percent with the clinical infection was HPV-16, and for warts HPV-11.

Vacinas contra rotavírus e papilomavírus humano (HPV) / Vaccines against rotavirus and human papillomavirus (HPV)

OBJETIVOS: Sintetizar as estratégias para a obtenção de uma vacina contra rotavírus e papilomavírus humano (HPV), enfatizando-se o estágio atual das investigações quanto à segurança, reatogenicidade, imunogenicidade e eficácia. FONTE DOS DADOS: Os artigos publicados de 1996 a 2006, particularmente ao longo dos últimos 5 anos, representaram a fonte primária (base de dados: MEDLINE, PubMed, NIH, EUA), conferindo-se destaque aos recentes estudos envolvendo uma vacina contendo rotavírus atenuado de origem humana e dois tipos de vacinas para HPV testadas em humanos: as profiláticas e as terapêuticas. SíNTESE DOS DADOS: Em relação às vacinas contra rotavírus, o contexto de estratégias compreendeu desde as preparações jennerianas até o advento da vacina com rotavírus atenuado de origem humana. Duas vacinas despontam como eficazes e seguras: uma, pentavalente, envolvendo vírus de bovinos e do homem; outra, de rotavírus atenuado oriundo da espécie humana, sendo que esta é avaliada em mais de 70.000 crianças no mundo. As vacinas contra HPV profiláticas visam impedir a infecção por esses vírus, enquanto que as vacinas terapêuticas pretendem tratar o indivíduo já infectado ou até o portador de uma lesão causada por HPV. As pesquisas com vacinas profiláticas começaram há alguns anos nos EUA e, hoje, aproximadamente 25.000 mulheres, em vários países, participam de estudos sobre essa vacina, que até o momento tem se mostrado segura, bem tolerada, altamente imunogênica e eficaz contra os tipos de HPV que causam as verrugas genitais e 70 por cento dos casos de câncer do colo do útero. CONCLUSÕES:Uma vacina eficaz e segura contra rotavírus resultará em impacto significativo quanto à doença grave por esse enteropatógeno. Um programa global de imunizações que consiga atingir 60 a 80 por cento das crianças durante os próximos 10 anos pode reduzir em pelo menos 50 por cento as hospitalizações e a mortalidade por rotavírus. Antecipa-se que a implementação de vacinas de elevada eficácia na prevenção de tumores benignos e malignos causados por alguns tipos de HPV leve a uma queda acentuada das taxas desses tumores, os quais afetam milhões de pessoas em todo o mundo.

Comparação de três protocolos de extração de DNA a partir de tecido fixado em formol e incluído em parafina / Comparison of three DNA extraction protocols from formaldehyde-fixed and paraffin-embedded tissues

OBJETIVO: Padronizar um método alternativo para extração de DNA a partir de tecido fixado em formol e conservado em arquivos de blocos de parafina, visando à realização de estudos retrospectivos. MÉTODOS: Comparou-se a eficiência de protocolos de extração de DNA a partir de tecido parafinado, para análise por reação em cadeia de polimerase (PCR), tomando-se como parâmetro um protocolo baseado em um kit comercial. Foram feitas extrações do DNA de 60 espécimes por três métodos: o protocolo A, baseado no kit GlassMAX; o B, utilizando-se o kit GFX TM; e o C, tendo como base o método de Banerjee et al.(2). A integridade e a suficiência do DNA presente na amostra foram avaliadas pela amplificação por PCR de um segmento de 110pb do gene da beta-globina humana, com visualização por meio de eletroforese em gel de poliacrilamida, corado pela prata. Resultados: Das 60 amostras analisadas, 45 apresentaram resultado positivo na PCR quando o DNA foi extraído por qualquer um dos três protocolos. Em seis amostras, a amplificação foi positiva apenas para o DNA extraído pelos protocolos A e C. Em três amostras, o resultado foi positivo apenas para o DNA extraído pelo protocolo A, e em duas, apenas para o DNA extraído pelo protocolo C. CONCLUSÕES: O protocolo C apresentou desempenho semelhante ao do protocolo A, com as vantagens de apresentar menor custo, dispensar o uso de kit comercial, além de não utilizar solventes orgânicos, revelando-se uma alternativa viável para a obtenção de DNA a partir de tecido fixado em formol e incluído em parafina.