Update on human papilloma virus - part I: epidemiology, pathogenesis, and clinical spectrum

Abstract Infection with human papilloma virus (HPV) is related to a great number of cutaneous and mucosal manifestations. The spectrum of HPV ranges from inapparent infections, through various clinical benign presentations including cutaneous and mucosal disease, to malignant and premalignant conditions. New HPV types are currently described in the literature; many of them are characterized as high-risk types due to their oncogenic potential. Knowledge regarding their epidemiology and pathogenesis is important to understand not only infection and disease processes, but also to formulate the clinical and laboratory basis for diagnosis, therapeutics, and prophylactic measures. This non-systematic review aims to discuss and to update those aspects, with an emphasis on relevant topics for dermatologists. HPV infection and related diseases in the Brazilian scenario are highlighted, including common dermatologic conditions seen at clinics as well as the condition of a public health problem as a sexually transmitted infection. The oncogenicity of the virus and the variety of clinical outcomes - especially in the immunocompromised individuals - are addressed.

Update on human papilloma virus - part I: epidemiology, pathogenesis, and clinical spectrum.

Infection with human papilloma virus (HPV) is related to a great number of cutaneous and mucosal manifestations. The spectrum of HPV ranges from inapparent infections, through various clinical benign presentations including cutaneous and mucosal disease, to malignant and premalignant conditions. New HPV types are currently described in the literature; many of them are characterized as high-risk types due to their oncogenic potential. Knowledge regarding their epidemiology and pathogenesis is important to understand not only infection and disease processes, but also to formulate the clinical and laboratory basis for diagnosis, therapeutics, and prophylactic measures. This non-systematic review aims to discuss and to update those aspects, with an emphasis on relevant topics for dermatologists. HPV infection and related diseases in the Brazilian scenario are highlighted, including common dermatologic conditions seen at clinics as well as the condition of a public health problem as a sexually transmitted infection. The oncogenicity of the virus and the variety of clinical outcomes - especially in the immunocompromised individuals - are addressed.

Prevalence of oncogenic human papillomavirus in patients with cervical lesion. / Prevalencia del virus del papiloma humano oncogénico en pacientes con lesión cervical.

BACKGROUND: High risk human papillomavirus (hrHPV) infection is associated with the development of cervical cancer (CC) in 99.7%. The prevalence of HPV varies according to the geographic region, lesion degree, method of detection, among other variables. OBJECTIVE: To determine the prevalence of hrHPV and identify some risk factors in a group of women with cervical lesions from Mexico City. MATERIAL AND METHODS: Of 421 women, 310 were included. Questionnaires of risk factors were administered, and cervical samples which included the entire spectrum of cervical lesions according to the Bethesda system were obtained. HPV genotyping was made with INNO-LiPA system. Population characteristics were analyzed with descriptive statistics. Risk factors' odds ratio (OR) was calculated with chi squared using SPSS software, version 24.0. RESULTS: 91.6% of the samples were positive for hrHPV. The prevalent types were 16, 66, 52 and 51. By age group there were not statistically significant differences in the risk of HPV infection. Having had three or more sexual partners increased the risk of infection by hrHPV (OR: 2.99; 95% confidence interval [95% CI]: 1.247.24). Sexually transmitted diseases increased the probability of infection by hrHPV different to types 16, and 18 (OR: 2.47; 95% CI, 1.24-7.24 and 1.50-4.06). CONCLUSIONS: The high prevalence of types 66, 52 and 51 is a finding that has not been described previously in our population. We hope that this study will help to improve health services in order to decrease the incidence of cervical ­cancer.

INTRODUCCIÓN: La infección por el virus del papiloma humano (VPH) de alto riesgo oncogénico (VPHar) se asocia al cáncer cervicouterino en el 99.7% de los casos. La prevalencia de VPH varía según la región geográfica, el grado de lesión y el método de detección, entre otras variables. OBJETIVO: Determinar la prevalencia de VPHar e identificar factores de riesgo en mujeres con lesión cervical de la Ciudad de Mexico. MATERIAL Y MÉTODOS: De 421 mujeres, se incluyeron 310. Se aplicaron cuestionarios y se obtuvieron muestras que incluyeron todo el espectro de las lesiones cervicales según el sistema Bethesda. La tipificación del VPH se hizo mediante el sistema INNO-LiPA. Las características de la población se analizaron con estadística descriptiva. Con la prueba de chi cuadrada se calculó la razón de momios (RM) de los factores de riesgo con el programa SPSS, versión 24.0. RESULTADOS: El 91.6% de las muestras fueron positivas para VPHar. Los VPH prevalentes fueron los tipos 16, 66, 52 y 51. Por edad no hubo significación estadística para riesgo de infección por VPHar. Haber tenido tres o más parejas sexuales elevó el riesgo de infección por HPVar (RM: 2.99; intervalo de confianza del 95 [IC 95%]: 1.247.24). Las infecciones de transmisión sexual favorecieron el riesgo de infección por otros VPHar distintos de los tipos 16 y 18 (RM: 2.47; IC 95%: 1.24-7.24 y 1.50-4.06). CONCLUSIÓN: La elevada prevalencia de VPH 66, 52 y 51 es un hallazgo que no ha sido descrito previamente en nuestra población. Esperamos que este estudio contribuya a mejorar los programas de los servicios de salud dirigidos a disminuir la incidencia de cáncer cervicouterino.

Current status and progress in the research for viral nfection-associated gastric cancer / 国际外科学杂志

Gastric cancer is one of the malignant tumors with high morbidity and high mortality in China.Research has shown that viral infection is closely related to the occurrence of gastric cancer.EpsteinBarr virus-associated gastric cancer characterized by EB virus infection has been classified as a subtype of gastric cancer,whose epidemiology,pathogenesis,clinical and histopathologic features have been studied in detail.At the same time,oncolytic viruses reveal the inhibitory effect of the virus on tumors,and their ability to target and kill tumor cells is used in the treatment of some advanced cancers.This article will review the research advances about relevance to gastric cancer of several viruses that have been reported and the latest progress in anticancer mechanisms and combined therapies for oncolytic viruses.

Acceptance of human papillomavirus vaccination and associated factors in the city of Resistencia, Argentina.

INTRODUCTION: In Argentina, every year, 3000 new cases of cervical cancer are diagnosed and more than 2000 deaths occur as a result of this disease. Human papillomavirus (HPV) is the main risk factor for cervical carcinogenesis. OBJECTIVES: To establish the extent of acceptance of HPV vaccines and associated factors among legal guardians of candidate girls in an area of Resistencia, Chaco. METHODS: Qualitative and quantitative study. A single randomized sampling was done based on school enrollment lists. Guardians who reported making decisions regarding girls' health in 2012 were included. A structured questionnaire made up of four constructs was used to measure overall acceptability. The association between overall acceptability and sociodemographic outcome measures was assessed. RESULTS: The rate of acceptance was 46.6% (95% confidence interval: 34.8-58.6). Among guardians, 84.2% were women; their mean age was 38.3 years old (95% confidence interval: 36.7-39.8). Religion was practiced by 86.8% (77.1-93.5), 55.2% were Catholic and 44.8%, Evangelical Protestants. Guardians with more than one candidate girl for the vaccine accounted for 18.9%. Also, 85.5% referred having heard about the virus at some point, and 52.7% knew that a vaccine could prevent it. Acceptance was significantly higher among guardians of those girls who had received the first vaccine dose (OR: 8.02, 95% confidence interval: 2.29-28.01, p= 0.0011). CONCLUSIONS: The rate of acceptance was low and no association was observed between sociodemographic and psychosocial factors and the decision to have girls vaccinated with the HPV vaccine.

INTRODUCCIÓN: En Argentina, se diagnostican 3000 nuevos casos y más de 2000 muertes por cáncer de cuello uterino cada año. El virus del papiloma humano es el principal factor de riesgo en la carcinogénesis cervical. OBJETIVOS: Determinar el nivel de aceptación de la vacuna contra el virus del papiloma humano por parte de los tutores de las niñas candidatas y los factores asociados en un área de Resistencia, Chaco. MÉTODOS: Estudio cualicuantitativo. Se utilizó un muestreo aleatorio simple sobre la base de listas escolares. Se incluyeron los tutores que refirieron tomar decisiones respecto a la salud de sus niñas, en el año 2012. Se utilizó un cuestionario estructurado en 4 constructos, que medían la aceptabilidad global. Se estudió la asociación entre aceptabilidad global y las variables sociodemográficas. RESULTADOS: La frecuencia de aceptación fue 46,6% (IC 95%: 34,8-58,6). De los tutores, el 84,2% fueron mujeres; la media de edad fue 38,3 años (IC 95%: 36,7-39,8). La frecuencia de práctica de religión fue 86,8% (77,1-93,5); el 55,2% practicaban la religión católica y el 44,8%, evangelista. El 18,9% tenia más de una niña candidata a recibir la vacuna. El 85,5% refirió que había escuchado hablar del virus en algún momento y el 52,7% conocía la existencia de la vacuna para prevenirlo. La aceptación fue significativamente mayor en los tutores de las niñas que habían recibido la primera dosis de la vacuna (OR 8,02; IC 95%: 2,29-28,01; p= 0,0011). CONCLUSIONES: La frecuencia de aceptación fue baja y no se encontró una asociación de los factores sociodemográficos y psicosociales con la decisión de vacunar a las niñas contra el virus del papiloma humano.

Aceptación de la vacuna contra el virus del papiloma humano y los factores asociados en la ciudad de Resistencia, Chaco / Acceptance of human papillomavirus vaccination and associated factors in the city of Resistencia, Argentina

Introducción. En Argentina, se diagnostican 3000 nuevos casos y más de 2000 muertes por cáncer de cuello uterino cada año. El virus del papiloma humano es el principal factor de riesgo en la carcinogénesis cervical. Objetivos. Determinar el nivel de aceptación de la vacuna contra el virus del papiloma humano por parte de los tutores de las niñas candidatas y los factores asociados en un área de Resistencia, Chaco. Métodos. Estudio cualicuantitativo. Se utilizó un muestreo aleatorio simple sobre la base de listas escolares. Se incluyeron los tutores que refirieron tomar decisiones respecto a la salud de sus niñas, en el año 2012. Se utilizó un cuestionario estructurado en 4 constructos, que medían la aceptabilidad global. Se estudió la asociación entre aceptabilidad global y las variables sociodemográficas. Resultados. La frecuencia de aceptación fue 46,6% (IC 95%: 34,8-58,6). De los tutores, el 84,2% fueron mujeres; la media de edad fue 38,3 años (IC 95%: 36,7-39,8). La frecuencia de práctica de religión fue 86,8% (77,1-93,5); el 55,2% practicaban la religión católica y el 44,8%, evangelista. El 18,9% tenia más de una niña candidata a recibir la vacuna. El 85,5% refirió que había escuchado hablar del virus en algún momento y el 52,7% conocía la existencia de la vacuna para prevenirlo. La aceptación fue significativamente mayor en los tutores de las niñas que habían recibido la primera dosis de la vacuna (OR 8,02; IC 95%: 2,29-28,01; p= 0,0011). Conclusiones. La frecuencia de aceptación fue baja y no se encontró una asociación de los factores sociodemográficos y psicosociales con la decisión de vacunar a las niñas contra el virus del papiloma humano.

Introduction, In Argentina, every year, 3000new cases of cervical cancer are diagnosed and more than 2000 deaths occur as a result of this disease. Human papillomavirus (HPV) is the main risk factor for cervical carcinogenesis. Objectives. To establish the extent of acceptance of HPV vaccines and associated factors among legal guardians of candidate girls in an area of Resistencia, Chaco. Methods. Qualitative and quantitative study. A single randomized sampling was done based on school enrollment lists. Guardians who reported making decisions regarding girls' health in 2012 were included. A structured questionnaire made up offour constructs was used to measure overall acceptability. The association between overall acceptability and sociodemographic outcome measures was assessed. Results. The rate of acceptance was 46.6% (95% confidence interval: 34.8-58.6). Among guardians, 84.2% were women; their mean age was 38.3 years old (95% confidence interval: 36.7-39.8). Religion was practiced by 86.8% (77.1-93.5), 55.2% were Catholic and 44.8%, Evangelical Protestants. Guardians with more than one candidate girl for the vaccine accounted for 18.9%. Also, 85.5% referred having heard about the virus at some point, and 52.7% knew that a vaccine could prevent it. Acceptance was significantly higher among guardians of those girls who had received the first vaccine dose (OR: 8.02, 95% confidence interval: 2.29-28.01, p= 0.0011). Conclusions. The rate of acceptance was low and no association was observed between sociodemographic and psychosocial factors and the decision to have girls vaccinated with the HPV vaccine.

Pathology of tumors in fish associated with retroviruses: a review.

Thirteen proliferative diseases in fish have been associated in the literature with 1 or more retroviruses. Typically, these occur as seasonal epizootics affecting farmed and wild fish, and most lesions resolve spontaneously. Spontaneous resolution and lifelong resistance to reinfection are 2 features of some piscine retrovirus-induced tumors that have stimulated research interest in this field. The purpose of this review is to present the reader with the epidemiological and morphological features of proliferative diseases in fish that have been associated with retroviruses by 1 or more of the following methods: detection of C-type retrovirus-like particles or reverse transcriptase activity in tumor tissues; successful tumor transmission trials using well-characterized, tumor-derived, cell-free inocula; or molecular characterization of the virus from spontaneous and experimentally induced tumors. Two of the diseases included in this review, European smelt spawning papillomatosis and bicolor damselfish neurofibromatosis, at one time were attributed to a retroviral etiology, but both are now believed to involve additional viral agents based on more recent investigations. We include the latter 2 entities to update the reader about these developments.

Prevalencia del VPH en el proceso de malignización de lesiones de vías aérodigestivas superiores / HPV prevalence on malignant lesion process of the upper aerodigestive tract

Los papilovirus o virus del papiloma son considerados el grupo más prevalente de virus causantes de tumores de cabeza y cuello asociados a la infección con virus del papiloma humano (VPH). Según revisiones sistemáticas en México y Colombia, la prevalencia de VPH en el proceso de malignización de lesiones de vías aerodigestivas superiores (VADS) se presenta con una incidencia en orofarìnge de 35,6 por ciento, en cavidad oral 23,5 por ciento y en laringe 24,0 por ciento. En ésta revisión también destacan los genotipos de VPH de bajo riesgo (VPH 31, 45, 6 y 11), los cuales inducen la aparición de algunas lesiones precancerosas. La falta de un diagnostico oportuno del VPH y de las lesiones que deriven de este virus, puede complicar el tratamiento del mismo. En cuanto a los métodos de su diagnóstico, se demuestra la efectividad del método PCR-RFLP como el punto de partida del monitoreo de la infección y su progresión a cáncer. Estos métodos pueden permitir comprender la virulencia del mismo y contribuir a la disminución de las tasas de incidencia a causa de las imprecisiones de diagnostico clínico por metodologías convencionales ya que dificultan la detección precoz del cáncer de las vías aerodigestivas superiores.

Papilovirus or papillomaviruses are considered the most prevalent group of viruses that cause tumors of head and neck associated with infection with human papilloma virus (HPV). According to systematic reviews in Mexico and Colombia, the prevalence of HPV in the process of malignant lesions of the upper aerodigestive tract, can be shown with a clinical prevalence of 35,6 percent in oropharynx, 23.5 percent in oral cavity and 24.0 percent in larynx. This review highlights the genotypes of low-risk HPV (HPV 31, 45, 6 and 11), which induce the appearance of precancerous lesions. It demonstrates the effectiveness of PCR-RFLP method as a starting point for the monitoring of infection and progression to cancer this method can facilitate understanding of its virulence activity and contribute to reduced incidence rates because of the inaccuracies of clinical diagnosis by conventional methods that hinder the early detection of cancer of upper aerodigestive tract.

Avaliação da eficácia do cidofovir na papilomatose respiratória recorrente juvenil / Efficacy of cidofovir in recurrent juvenile respiratory papillomatosis

O uso do cidofovir para papilomatose respiratória recorrente juvenil (PRRJ) ainda não tem estudos caso-controle suficientes que comprovem sua eficácia em literatura. OBJETIVO: Avaliar fatores que influenciem o prognóstico da PRRJ, e observar a atuação do cidofovir na erradicação da PRRJ. DESENHO DO ESTUDO: Retrospectivo. MATERIAIS E MÉTODOS: 22 crianças com PRRJ foram avaliadas num centro terciário. Todas as crianças foram submetidas ao tratamento cirúrgico, seguido (Grupo 2) ou não (Grupo 1) pelo uso do cidofovir. A idade ao diagnóstico foi correlacionada ao escore de Derkay e à evolução da doença. Os Grupos 1 e 2 tiveram suas evoluções comparadas entre si. RESULTADOS: Quinze crianças foram consideradas curadas, 8 no Grupo 2 e 7 no Grupo 1. Houve uma correlação negativa entre idade e Escores Total e Clínico (P<0,05). O número médio de cirurgias necessárias para controlar a doença foi semelhante entre os Grupos, mas a duração do tratamento até remissão foi significativamente maior no Grupo 1 quando comparado ao Grupo 2 (P<0,05). CONCLUSÕES: A PRRJ é mais agressiva quanto mais nova a idade do paciente ao diagnóstico. Pacientes tratados com cidofovir apresentaram duração significativamente menor de tratamento até erradicação da PRRJ do que os submetidos apenas ao tratamento cirúrgico.

The efficacy of cidofovir in juvenile recurrent respiratory papillomatosis (JRRP) remains uncertain due to the lack of published case-control studies. AIM: To establish factors affecting the progression of JRRP prognosis, and to evaluate cidofovir for eradicating JRRP. STUDY DESIGN: Retrospective. METHODS: 22 children with JRRP were evaluated at a referral center. All children underwent surgical debulking, followed by cidofovir injection (Group 2) or not (Group 1). Age at diagnosis was correlated with the Derkay score and disease outcome. Disease progression was compared between groups 1 and 2. RESULTS: fifteen children were considered disease-free; 8 were in Group 2 and 7 in Group 1. Age and total and clinical scores (P<0.05) were negatively correlated. The mean number of surgeries required to control the disease was identical in both groups; the duration of treatment until remission was significantly higher in Group 1 (P<0,05). CONCLUSION: JRRP is more aggressive in earlier onset disease. The duration of treatment was significantly lower in patients treated with cidofovir until eradication of JRRP compared to patients treated with surgery only.

Aplicação local de cidofovir como tratamento adjuvante na papilomatose laríngea recorrente em crianças / Local application of cidofovir as adjuvant therapy in recurrent laryngeal papillomatosis in children

OBJETIVO: Avaliar a eficácia da aplicação local de cidofovir em associação com o tratamento cirúrgico na papilomatose laríngea recorrente (PLR) em crianças. Desenho do estudo: Prospectivo. MÉTODOS: Quatorze pacientes, com idade média de 4.7 anos e com duas ou mais recidivas após tratamento cirúrgico, foram submetidos à ressecção dos papilomas e injeção de 22.5 mg de cidofovir (7,5 mg/ml) no tecido de onde as lesões foram removidas. Após intervalos de 2-3 semanas, a mesma dose de cidofovir foi repetida duas ou três vezes. Em caso de recidiva, um novo ciclo de cirurgia seguido de aplicações locais de cidofovir era reiniciado. Cinco crianças apresentavam HPV-6 e cinco HPV-11; em quatro casos a tipagem não foi realizada. RESULTADOS: Antes do início do estudo, os pacientes eram submetidos, em média, a duas cirurgias por ano para o controle das recidivas; após o tratamento com cidofovir, a taxa anual de cirurgia diminuiu para 1,1 (p = 0,013). O intervalo médio entre as recidivas antes do início do estudo era de 1.6 meses; ao final do estudo, o intervalo aumentou para 4,4 meses (p = 0,014). Os pacientes com HPV-6 não apresentaram alteração significante nos intervalos entre as recidivas após o tratamento com cidofovir, enquanto 60 por cento das crianças com HPV-11 encontravam-se livres de doença ao final do estudo. CONCLUSÃO: O cidofovir é um adjuvante eficaz no tratamento da PLR em crianças, quando utilizado sob a forma de aplicações locais em associação com a ressecção cirúrgica das lesões. O HPV-11 pode ser mais susceptível aos efeitos benéficos do cidofovir.

OBJECTIVE: Evaluate the efficacy of local application of cidofovir in association with surgical treatment of recurrent laryngeal papillomatosis in children. Study design: Prospective. METHODS: Fourteen patients, with an average age of 4.7 years and with two or more relapses after surgical treatment, were submitted to resection of the papillomas and injection of 22.5 mg of cidofovir (7.5 mg/ml) in the tissue where the lesions had been removed. After 2 to 3 week intervals, the same dose of cidofovir was repeated two or three times. In the case of relapse, a new cycle of surgery followed by local applications of cidofovir was repeated. Five children presented HPV-6 and five HPV-11, while in four, the type was not determined. RESULTS: Before beginning of the study, patients were submitted, on the average, to 2 operations a year for control of relapses. After treatment with cidofovir, the annual rate for surgery dropped to 1.1 (p = 0.013). The average interval between relapses before beginning of the study was 1.4 months; at the end of the study, the interval reached 4.4 months (p = 0.014). Patients with HPV-6 did not show a significant change in the intervals between relapses after treatment with cidofovir, while 60 percent of the children with HPV-11 were disease free at the study end. CONCLUSION: Cidofovir was found to be an effective adjuvant in the treatment of recurrent laryngeal papillomatosis in children, when used in the form of local applications in association with surgical resection of the lesions. HPV-11 may be more susceptible to the beneficial effects of cidofovir.

Establishment of HBV-Marker-Producing Nude Mice Model of Human Transplanted Liver Cancer / 广州中医药大学学报

【Objective】To establish a HBV-marker-producing nude mice model of human transplanted liver cancer(HTLC).【Methods】2.2.15 cells,a HePG2 cell line transfected with HBV genome,were injected subcutaneously into athymic BALB/c-nu mice aged 4～6 weeks.The growth of tumor was observed every week.After 36 days the nude mice were executed and HBV markers of HBsAg,HBeAg,and HBV-DNA as well as alpha-fetoprotein(AFP)in serum were detected.The pathological features of tumor tissues were examined under light microscope.【Results】The incidence of HTLC and the time of HTLC appearing were correlated with the number of transplanted 2.2.15 cells.Serum HBsAg,HBeAg,and HBV-DNA were positive in the HTLC transplanted mice,the serum content of AFP was(350?11.5) ?g/L,and pathological changes under light microscope were similar to human,indicating that the model has some similar histological characteristics of the human liver cancer infected by HBV.【Conclusion】The nude mice model of human transplanted liver cancer,which can produce HBV markers,is established successfully in this study.