Human papillomavirus infections and renal transplantation: a review / Infecções causadas por papilomavírus humanos e transplante renal: uma revisão

The immune suppressive therapy in renal allograft recipients provides a favorable environment to the development of viral infections. Among them,human papillomavirus (HPV) infections are usually related to potential life-threatening mucocutaneous neoplasias. Data from clinical surveys suggestthat transplant recipients may have up to 5-fold increased risk of developing multiple malignancies due to the increased susceptibility to persistent HPV infection. High risk HPV induced oncogenesis is a multi-step process in which a persistent infection is the initiating causative event, though subsequentgenetic and epigenetic alterations may be necessary for malignant transformation. The main tumoral types associated with persistent HPV infection areanogenital, oral and skin cancers, common conditions in transplant recipients and responsible for substantial morbidity and mortality. Since prophylactic vaccines with high rates of efficacy have been approved for human population, studies to evaluate its immunogenicity and efficacy should be considered forlong-term survivors after allogeneic transplantation. Hence, we conducted an extensive revision published data for the last 10 years regarding the theme.To achieve our objectives, we searched in diverse data basis such as Lilacs, ScIELO, Medline, Scopus. We concluded that, concerning the increase in thepopulation of transplant recipients as well as in the incidence of HPV associated diseases, measures for prevention and control are necessary, and includecapaciting human resources and the use of last generation methodologies of diagnosis and prophylaxis.

A terapia imunossupressora em pacientes receptores de transplante renal fornece um ambiente favorável ao desenvolvimento de infecções virais. Dentreestas infecções, aquelas causadas pelos papilomavírus humanos (HPV) são geralmente associadas a neoplasias mucocutâneas que podem ameaçar asobrevida pós-transplante. Pesquisas clínicas sugerem que receptores de transplante podem apresentar um risco até cinco vezes maior de desenvolverem quadros de doenças malignas múltiplas, devido à maior frequência da persistência do HPV. A oncogênese induzida por HPV de alto risco é um processo demúltiplos estágios, no qual a infecção persistente é o evento fundamental, apesar de alterações genéticas e epigenéticas adicionais serem necessárias para a transformação maligna. Os principais tipos tumorais relacionados à infecção persistente por HPV são os cânceres anogenitais, orais e de pele, comunsem receptores de transplante e responsáveis por grande morbidade e mortalidade. Uma vez que vacinas profiláticas de alta eficácia contra a infecçãopelo HPV foram aprovadas para uso na população humana, estudos para avaliar a imunogenicidade e eficácia destas vacinas em imunossuprimidos são recomendáveis. Assim, objetivamos fazer extensa revisão sobre o tema. Para tal, pesquisamos o assunto nas bases de dados Lilacs, ScIELO, Medline,Scopus nos últimos 10 anos. Concluímos que, com o aumento na população de receptores de transplantes e a crescente incidência das doenças associadasao HPV, medidas de prevenção e controle se fazem necessárias e englobam desde a formação de profissionais capacitados até a aplicação de metodologias de diagnóstico e profilaxia, de última geração.

Detection of human herpesvirus 6 and 7 DNA in saliva from healthy adults from Rio de Janeiro, Brazil

In this study, we aimed to evaluate virus shedding in the saliva of healthy adults from the metropolitan region of the city of Rio de Janeiro, Brazil, in order to verify the prevalence of both human herpesviruses 6 and 7 (HHV-6, HHV-7). The studied group comprised 182 healthy individuals at Pedro Ernesto University Hospital, who were being seen for annual odontologic revisions. Saliva specimens were subjected to a multiplex polymerase chain reaction (PCR) to detect the presence of HHV-6A, HHV-6B and HHV-7. The total Roseolovirus DNA prevalence was 22.4 percent. The PCR detected a HHV-6 prevalence of 9.8 percent, with HHV-6A detected in 7.1 percent of the samples and HHV-6B in 2.7 percent. HHV-7 DNA was revealed in 12.6 percent of the studied cases. Multiple infections caused by HHV-6A and 7 were found in 2.1 percent of the samples. No statistical differences were observed regarding age, but for HHV-7 infection, an upward trend was observed in female patients. Compared to studies from other countries, low prevalence rates of herpesvirus DNA were detected in saliva from the healthy individuals in our sample. PCR methodology thus proved to be a useful tool for Roseolovirus detection and it is important to consider possible geographic and populations differences that could explain the comparatively low prevalence rates described here.

Update in the human papillomavirus infection prevalence rates and risk fators associated with penile cancer cases / Atualização no conhecimento acerca da prevalência das infecções Causadas pelos papilomavírus humanos e fatores de risco associados aos casos de câncer de pênis

O carcinoma de pênis é uma doença rara e potencialmente mutilante, com etiologia ainda pouco conhecida. A infecção pelo papilomavírus humano (HPV) parece ter um papel importante no desenvolvimento de um subgrupo desses carcinomas e a sua presença parece estar relacionada com determinados tipos histológicos. A prevalência do HPV em tumores de pênis é descrita como sendo associada a uma variedade de alterações morfológicas. Recentemente,houve um aumento de conhecimento acerca da patogênese do câncer de pênis, dos fatores de risco associados ao desenvolvimento das lesões precursoras relacionadas com essa doença. Embora o carcinoma de pênis seja reconhecido como um processo que ocorre em várias etapas, demonstrando um perfil policlonal, uma parte dos carcinomas de pênis é atribuída à infecção pelo HPV de alto risco, enquanto nos outros carcinomas de pênis, mecanismos moleculares independentes do HPV podem apresentar papel subjacente relevante. Entretanto, mais pesquisas sobre os mecanismos por trás da carcinogênese são necessárias.

Penile carcinoma is an uncommon and potentially mutilating disease with a still unknown etiology. Human papillomavirus (HPV) infection seems to playan important role in the development of a subset of these carcinomas and its presence is thought to be related to the histological type of the lesion. HPV prevalence in penile tumors is reported to be associated to a variety of morphological changes. In recent years, increased insight has been gained into the pathogenesis of penile cancer, the risk factors associated with penile cancer development and the clinical and histological precursor lesions related to this disease. Although penile carcinoma is recognized to be a multi-step process showing a polyclonal profile, a proportion of penile carcinoma is attributable to high risk HPV infection, while in the remaining penile cancers molecular mechanisms independent of HPV are likely to represent the more common underlying events. However, research on the mechanisms behind penile carcinogenesis is warranted.

Risk factors associated with human papillomavirus infection in two populations from Rio de Janeiro, Brazil

We investigated human papillomavirus (HPV) infection in two female populations from diverse socio-economic strata from the state of Rio de Janeiro and we also investigated the possible co-factors related to infection and the progression to cancer. In Group I, the reference group of this study, 10.7 percent of the patients presented HPV infection, as detected by generic PCR, while in Group II (low socio-demographic conditions) HPV was detected in 31.1 percent of the samples. HPV16 was the most prevalent virus type found in both Groups I and II (5.3 percent and 10 percent, respectively), followed by HPV 18 (1.3 percent and 4.7 percent, respectively). Although only a small sample was analysed, we detected differences among the groups regarding the rates of HPV infection, HPV types, age, ethnicity, familial income, schooling, marital status, parity, tobacco smoking and oral contraceptive use. For Group I, the Papanicolaou test was the most powerful independent factor associated with HPV status, followed by an age of under 30 years old, the number of sexual partners and black ethnicity. Our data are in agreement with the co-factors that are typically described for the developed world. For Group II, the Pap test was also the most relevant variable that was analysed, but the history of other sexually transmitted diseases and the use of alcohol were additional factors that were implicated in infection. These findings point out the need for the development of general and specific strategies for HPV screening of all Brazilian women.

Comparação de dois pares de oligonucleotídeos utilizados na reação em cadeia da polimerase para detecção de Papilomavírus Humanos em esfregaços cervicais / Comparison of two pairs of primers used in polymerase chain reaction for the detection of Hunan Papillomaviruses in cervical smears

Introdução: o câncer de colo de útero é a neoplasia mais frequente em mulheres de países em desenvolvimento. Grande parte desses casos é causada por infecção persistente com diferentes tipos de papilomavírus humano (HPV) classificados em alto e baixo risco de acordo com o potencial oncogênico. Atualmente, acredita-se que a melhor rotina de identificação e acompanhamento das lesões por HPV de forma a prevenir o câncer cervical é a combinação da técnica de Papanicolaou com a reação em cadeia por polimerase (PCR) na qual ocorre a amplificação de regiões conservadas do genoma viral, com uso de primers degenerados e em seguida identificação do tipo viral. O primer mais utilizado em todo o mundo é o MY09/11, com boa sensibilidade e especificidade. Recentemente, foi descrito na literatura um novo conjunto de primers consensuais denominado PGMY reformulando o primer MY e adicionando um novo primer HMBO visando diminuir perdas do MY (falso negativo). Objetivo: comparar os dois pares de primers, MY e PGMY, a fim de apontar aquele mais adequado para o rastreamento de infecções causadas por HPV no colo uterino pela técnica de reação em cadeia da polimerase. Métodos: avaliamos 116 amostras de esfregaços cervicais. Após a extração do DNA, a técnica de PCR foi realizada de acordo com os protocolos descritos na literatura. Resultados: através desse trabalho, observamos que o par de primers PGMY apresenta maior sensibilidadee especificidade na detecção do DNA do HPV quando comparado com o par de primers MY, além de melhores valores preditivos negativo e positivo. Conclusão: o novo par de primers PGMY, deve ser usado para substituir o par MY a fim de melhorar a detecção do DNA viral.

Introduction: cervical cancer is the most frequent neoplasia among the women of countries in development. Great part of those cases is caused by persistent infection with different types of Human Papillomavirus (HPV) classified as high and low risk, according to the risk of cervical cancer development. Nowadays, it is believed that the best identification routine and follow up of the lesions in order to prevent the malignant transformation is the combination of the technique of Papanicolaou with the polymerase chain reaction (PCR), in which the amplification of conserved areas of the viral genome occurs, with use of degenerate primers, followed by type identification. The degenerate primers MY 09/11 are used worldwide, presenting good sensibility and specificity. Recently, a new group of consensual primers denominated PGMY was described in the literature reformulating the primer MY and adding a new primer HMBO seeking to reduce losses of MY (false negative). Objective: compare two pairs of primers, MY and PGMY, to discorer the most appropriate for the diagnosis of infections caused by HPV in the uterine cervix for the technique of Polymerase chain reaction. Methods: a hundred and sixteen samples from cervical smears were evaluated. After DNA extraction, the PCR was done according to the protocols described in the literature. Results: we observed that the primers pair PGMY presents better sensibility and specificity in the detection of DNA of HPV when compared to the primers pair MY, it also presents better negative and positive predictive values. Conclusion: the new primers pair PGMY should be used to substitute the pair MY to improve the detection of the viral DNA.

Avaliação do uso combinado do teste de triagem de papanicolaou e da reação em cadeia da polimerase para identificação de pacientes em risco de câncer cervical / Evaluation of the combined use of papanicolaou screen test and polymerase chain reaction for the identification of patients at risk of cervical cancer

Introduction: in the last few years, the interest on Human Papillomavirus (HPV) has emerged due to the evidence of their carcinogenic potential,especially on the female genital tract. In the last fi fty years, the screening diagnosis has been carried out by Papanicolaou test (Pap). Nevertheless,literature describes a high rate of false-negative and false-positive samples. Objective: since an early detection is crucial to diminish the risk of cervical cancer, we aimed to analyze the use of HPV DNA detection by PCR as complementary test to routine screening. Methods: nearly 450 female smears were obtained from the DNA Bank of the Virological Diagnosis Laboratory from UFF. HPV prevalence was evaluated by using MY09/11 consensus primers and was compared to Pap test. Results: our results showed that 67.5% of the studied samples were normal tissues, among them 85.6% were negative by PCR but 14.4% were HPV infected. The remaining 32.8% were altered by Pap test. Among them, HPV DNA detection by PCR revealed a prevalence of 56.7% in ASCUS, 87.5% in LSIL and 66,6% in carcinoma. Kappa index showed a good agreement between tests (0.80). The Positive Predictive Value was considered low (58%) pointing out that important cases may be misdiagnosed as false-negatives. On the other hand, the Negative Predictive Value was considered high (90,5%) indicating that PCR should not be used as a screening test, but as a complementary one, revealing true negatives when associated to a normal result in Pap test. HPV positive samples detected by MY PCR were typed and the prevalence obtained for the different types was: 48% HPV 16, 17% HPV 33, 13% HPV 18, 18% HPV 6 and 19% were undetermined because of non tested primers or technical problems. Conclusion: analyzing the results we concluded the combination of both tests is the best diagnostic procedure, allowing a more effi cient evaluation of cancer risk and thus helping in prevention programs.

Introdução: nos últimos anos, o interesse pelo estudo dos papilomavírus humanos (HPV) aumentou, uma vez demonstrada a evidência de seu potencial oncogênico, especialmente no trato genital feminino. A partir de 1950, o rastreamento das lesões genitais foi feito pelo teste de Papanicolaou (colpocitologia oncótica). Entretanto, a literatura o atribui altas taxas de falso-positivos e negativos. Objetivo: uma vez que a detecção precoce é crucial para prevenção do câncer cervical, analisamos o uso do PCR para detecção do DNA do HPV como teste complementar à atual rotina diagnóstica. Métodos: cerca de 450 esfregaços cervicais foram obtidos do banco de amostras do Laboratório de Diagnóstico Virológico da UFF. A prevalência do HPV foi avaliadapelo uso de primers consensuais MY09/11. Resultados: nossos resultados mostraram que 67,5% das amostras eram normais e dentre eles, 85,6% eram negativas pelo PCR, mas 14,4% estavam infectadas. As 32,5% amostras restantes tinham preventivo alterado e com alta prevalência de infecções por HPV, oscilando de 56,7% em ASCUS a 87,5% em LSIL. O índice Kappa apresentou boa concordância entre os testes (0,80). O valor preditivo positivo foi baixo (58%) indicando que casos relevantes podem ser subdiagnosticados como falso-negativos. Por outro lado, o valor preditivo positivo foi elevado (90,5%) revelando que o PCR, embora não deva ser usado como método de triagem, tem importante papel complementar ao preventivo, apontando os verdadeiros negativos, quando associado à colpocitologia oncótica normal. Amostras positivas para HPV pelo PCR-MY foram tipadas e a prevalência obtida revelou 48% HPV 16, 17% HPV 33, 13% HPV 18, 18% HPV 6 e 19% de HPV indeterminados. Conclusão: nossos resultados indicam que o uso combinado de ambos os testes parece ser a conduta diagnóstica mais adequada, permitindo avaliação efi ciente do risco de câncer e assim colaborar em programas de prevenção.