Vacuna del virus del papiloma humano: valoración bioética de la discriminación por sexo

La infección por el virus del papiloma humano (VPH) constituye la causa necesaria, aunque no suficiente, de la enfermedad de transmisión sexual más frecuente en el mundo, responsable del 4,5 % de todos los cánceres en ambos sexos. La vacunación frente al VPH, con niveles de eficacia y seguridad similares en ambos sexos, está dirigida básicamente a mujeres, para reducir la incidencia de infección y sus consecuencias, como el cáncer de cérvix. La transmisibilidad del virus en ambos sexos y la inmunidad colectiva que proporciona la vacunación universal hace que su extensión al sexo masculino constituya una cuestión no solo de salud pública, sino también un dilema bioético relacionado con la protección de la salud y la equitativa distribución de los recursos. Este trabajo aborda el análisis bioético de la extensión de la vacunación contra VPH a ambos sexos.

Human Papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide, responsible for 4.5 % of all cancers in both sexes. HPV vaccination, with similar levels of efficacy and safety in both sexes, is aimed at women to prevent cervical cancer. The transmissibility of the virus in both sexes and the herd immunity provided by universal vaccination makes its extension to the male sex a matter not only of public health but also a bioethical dilemma related to the protection of health and the equitable distribution of resources. This research addresses the bioethical analysis of the extension of HPV vaccination to both sexes.

A infecção pelo vírus do papiloma humano (HPV, na sigla em inglês) constitui a causa principal, ainda que não suficiente, da doença de transmissão sexual mais frequente no mundo, responsável por 4,5 % de todos os cânceres em ambos os sexos. A vacinação contra o HPV, com níveis de eficácia e segurança semelhantes em ambos os sexos, está orientada basicamente a mulheres, para reduzir a incidência de infecção e suas consequências, como o câncer do colo do útero. A transmissão do vírus em ambos os sexos e a imunidade coletiva que a vacinação universal promove fazem com que sua extensão ao sexo masculino constitua uma questão não apenas de saúde pública, mas também um dilema bioético relacionado com a proteção da saúde e a equitativa distribuição dos recursos. Nesse sentido, neste trabalho, é abordada a análise bioética da extensão da vacinação contra o HPV em ambos os sexos.

Lineage and phylogenetic analysis of HPV-16, -18 in saliva of HNSCC patients

Aim: Head and Neck Squamous Cell Carcinoma (HNSCC) is a global health problem whose incidence varies by geographic region and race according to risk factors. Human papillomavirus (HPV) infection is a significant risk factor for HNSCC. HPV-16 and HPV-18 are two forms of HPV that are carcinogenic. HNSCCs that are HPV positive have a better prognosis rather than HPV negative. The purpose of this research was to characterize HPV-16, -18 variations in the saliva of HNSCC patients by examining the genetic diversity of HPV-16, -18 utilizing the full E6, E7, and L1 genes. Methods:The case-control research included 15 patients with HNSCC and 15 healthy volunteers. Unstimulated entire saliva samples were obtained from the case and control groups by spitting method. Genomic DNA was isolated from all saliva samples. A PCR reaction was used to determine the presence of HPV in saliva. HPV-positive samples were genotyped and data were analyzed. We conducted a variant study on the HPV-16, -18 E6, and E7 genes. Results: Three patients with HNSCC were HPV-positive for two HPV genotypes out of 30 people diagnosed with HPV-DNA. HPV-16 and -18 were the most common genotypes. The HPV-16, -18 E6, and E7 genes were sequenced and compared to the HPV-16, -18 (E6, E7) prototype sequence. In all, HPV-16 lineages A1 and HPV-18 lineages A3 were discovered. Conclusion: Regarding the variation of HPV found in Iranian HNSCC patients, the need for further studies in HPV genotyping was seen. Sequencing HPV genes in HNSCC may help answer questions about HPV genotyping in the Iranian population. HPV genotype analysis aids in the development of vaccinations against HNSCC, halting disease progression and preventing HPV-associated HNSCC

Virus del papiloma humano de alto riesgo y factores asociados en mujeres de Ecuador / High-risk human papillomavirus and associated factors in women in Ecuador / Papilomavírus humano de alto risco e fatores associados nas mulheres equatorianas

El cáncer de cérvix en el 99% de los casos, es causado por el Virus del Papiloma Humano (VPH) de alto riesgo, su prevalencia es elevada en países de bajos ingresos debido a la escasez de recursos para realizar programas generalizados de detección precoz, inmunización y tratamiento adecuado. El objetivo de la investigación fue identificar la frecuencia y los factores de riesgo de las infecciones del VPH de alto riesgo, en mujeres de 21 a 65 años de tres cantones de la zona 6 del Ecuador, periodo 2019. Este fue un estudio analítico, de corte transversal; con una muestra de registros clínicos de 109 pacientes encuestadas a partir del proyecto de epidemiologia en la provincia de El Oro que cumplieron los criterios inclusión. Los datos se recogieron en un formulario validado por método Delphi. Se usó programa SPSS v 24, para la asociación de las variables: Intervalo de Confianza 95%, Chi cuadrado (con valor de p < 0.05), Odds Ratio. Los resultados observados fueron de 31 (28,4%) casos de pacientes con VPH AR, de estas se identificó como el genotipo más común al VPH AR 39 (11,01%) en las participantes del estudio, seguido del VPH AR 31 (8,26%). Fueron factores considerados asociados a la infección del VPH AR sin significancia estadística el inicio de la vida sexual (IVSA) antes de los 20 años (OR = 1,2); y el número de parejas sexuales igual o mayor a 2 (OR = 1,7). Se concluye que el inicio de vida sexual temprano y el numero compañeros sexuales fueron factores asociados, pero sin significancia estadística.

Cervical cancer in 99% of cases is caused by high-risk Human Papillomavirus (HPV), its prevalence is high in low-income countries due to the scarcity of resources for widespread early detection programs, immunization and adequate treatment. The objective of the research was to identify the frequency and risk factors of high-risk HPV infections in women aged 21 to 65 years in three cantons of zone 6 of Ecuador, period 2019. This was an analytical, cross-sectional study; with a sample of clinical records of 109 patients surveyed from the epidemiology project in the province of El Oro who met the inclusion criteria. Data were collected in a form validated by Delphi method. SPSS v 24 software was used for the association of variables: 95% confidence interval, Chi-square (with p value < 0.05), Odds Ratio. The results observed were 31 (28.4%) cases of patients with AR HPV, of which AR HPV 39 (11.01%) was identified as the most common genotype in the study participants, followed by AR HPV 31 (8.26%). Factors considered to be associated with AR HPV infection without statistical significance were sexual debut before the age of 20 years (OR = 1.2); and the number of sexual partners equal to or greater than 2 (OR = 1.7). It was concluded that early sexual debut and the number of sexual partners were associated factors, but without statistical significance.

Em 99% dos casos, o câncer cervical é causado pelo papilomavírus humano de alto risco (HPV), e sua prevalência é alta em países de baixa renda devido à escassez de recursos para a detecção precoce generalizada, imunização e programas de tratamento adequados. O objetivo da pesquisa era identificar a freqüência e fatores de risco para infecções por HPV de alto risco em mulheres entre 21-65 anos de idade em três cantões da zona 6 do Equador, período 2019. Este foi um estudo analítico de corte transversal com uma amostra de registros clínicos de 109 pacientes pesquisados do projeto de epidemiologia na província de El Oro que preenchiam os critérios de inclusão. Os dados foram coletados em um formulário validado pelo método Delphi. O software SPSS v 24 foi utilizado para a associação de variáveis: Intervalo de confiança 95%, Qui-quadrado (com valor de p < 0,05), Odds Ratio. Os resultados observados foram 31 (28,4%) casos de pacientes com AR HPV, dos quais AR HPV 39 (11,01%) foi identificado como o genótipo mais comum nos participantes do estudo, seguido por AR HPV 31 (8,26%). Fatores considerados associados à infecção por AR HPV sem significado estatístico foram a iniciação sexual (SAIV) antes dos 20 anos de idade (OR = 1,2); e número de parceiros sexuais igual ou maior que 2 (OR = 1,7). Concluímos que a estreia sexual precoce e o número de parceiros sexuais foram fatores associados, mas sem significado estatístico.

Estudio clínico y morfológica de las lesiones cervicales de alto grado. Hospital General Docente Abel SantamaríaCuadrado, 2019-2021 / Clinical and morphological study of high-grade cervical lesions. Abel Santamaría Cuadrado General Teaching Hospital, 2019-2021

RESUMEN Introducción: la neoplasia intraepitelial cervical es una lesión donde parte del espesor del epitelio está sustituido por células con atipias. Objetivo: caracterizar clínico y morfológicamente las lesiones cervicales de alto grado, en las pacientes del Hospital "Abel Santamaría Cuadrado", en el 2019 - 2021. Métodos: se realizó un estudio observacional, descriptivo y transversal. El universo estuvo representado por 472 pacientes que se les realizó histerectomía, conización o amputación cervical, la muestra coincide de manera intencional. Se empleó la prueba de dependencia u homogeneidad de proporciones para datos cualitativos y cuantitativos, y el Chi Cuadrado. Resultados: existió un predominio de pacientes con color de la piel blanca y las edades más frecuentes fueron entre 15 y 29 años de edad. De acuerdo a los resultados colposcópicos y edad, existió una preponderancia de las pruebas Schiller negativo y dentro de las positivo, el grupo más frecuente fue entre 40-49 años. En cuanto a la clasificación histológica, fueron más frecuentes las lesiones Cervicales de Alto Grado NICII, en la mayoría de los grupos de edades. Dado el grado de compromiso de los bordes en una conización, existe una superioridad de los bordes libres. Los más frecuentes fueron la infección por el virus del Papiloma Humano, y la edad temprana de la primera relación sexual. Conclusiones: el diagnóstico precoz y el adecuado control de los factores de riesgo constituyen las herramientas necesarias para la disminución de la mortalidad atribuibles al cáncer cérvico-uterino.

ABSTRACT Introduction: cervical intraepithelial neoplasia is a lesion where part of the thickness of the epithelium is replaced by cells with atypia. Objective: to clinically and morphologically characterize high-grade cervical lesions in patients at the "Abel SantamaríaCuadrado" Hospital in 2019 - 2021. Methods: an observational, descriptive and cross-sectional study was conducted. The universe was represented by 472 patients who underwent hysterectomy, conization or cervical amputation, matching the sample intentionally. The test of dependence or homogeneity of proportions was used for qualitative and quantitative data, as well as the Chi-square test. Results: there was a predominance of patients with white skin color and the most frequent ages were between 15 and 29 years old. According to colposcopic findings and age, there was a preponderance of negative Schiller tests and within the positive ones, the most frequent group was between 40-49 years old. In terms of histological classification, High Grade CIN II cervical lesions were more frequent in most age groups. Given the degree of edge involvement in a conization, there is a superiority of free edges. The most frequent were infection by the Human Papilloma Virus, and early age of first sexual intercourse. Conclusions: early diagnosis and adequate control of risk factors are the necessary tools to reduce mortality attributable to cervical-uterine cancer.

Fatores associados à infecção pelo papilomavírus humano na gestação: Uma revisão integrativa / Factores asociados a la infección por el virus del papiloma humano durante el embarazo: Una revisión integradora / Factors associated with human papillomavirus infection during pregnancy: An integrative review

Objetivo: Identificar os fatores associados à infecção pelo papilomavírus humano em gestantes. Método: Revisão integrativa realizada nas seguintes bases de dados: BDENF, LILACS, MEDLINE e IBECS. Foram utilizados os seguintes descritores: "Papilomavirus Humano", "HPV", "Gravidez", "Infecções Sexualmente Transmissíveis" e "IST" (com respectivas traduções para o inglês). Resultados: Seis artigos compuseram a amostra final deste estudo. O design de pesquisa mais prevalente foi o estudo transversal (n: 03). Verificou-se que os fatores associados à infecção pelo HPV estavam relacionados a características sociodemográficas (menor idade, baixa escolaridade, estado civil solteira e consumo de álcool na gestação) e maternas (multiparidade). Conclusão: Verificou-se que alguns fatores podem estar associados à presença de infecção pelo HPV em gestantes, como características sociodemográficas e maternas. Faz-se necessário que os profissionais de saúde tenham um olhar mais atento a este público, afim de contribuir para disseminação da informação e consequente prevenção.(AU)

Objective: To identify factors associated with human papillomavirus infection in pregnant women. Method: Integrative review carried out in the following databases: BDENF, LILACS, MEDLINE and IBECS. The following descriptors were used: "Papilomavirus Humano", "HPV", "Gravidez", "Infecções Sexualmente Transmissíveis" and "IST" (with respective translations into English). Results: Six articles made up the final sample of this study. The most prevalent research design was the cross-sectional study (n: 03). It was found that the factors associated with HPV infection were related to sociodemographic (younger age, low education, single marital status and alcohol consumption during pregnancy) and maternal (multiparity) characteristics. Conclusion: It was found that some factors may be associated with the presence of HPV infection in pregnant women, such as sociodemographic and maternal characteristics. It is necessary that health professionals have a closer look at this public, in order to contribute to the dissemination of information and consequent prevention.(AU)

Objetivo: Identificar los factores asociados a la infección por el virus del papiloma humano en mujeres embarazadas. Método: Revisión integrativa realizada en las siguientes bases de datos: BDENF, LILACS, MEDLINE e IBECS. Se utilizaron los siguientes descriptores: "Papilomavirus Humano", "HPV", "Gravidez", "Infecções Sexualmente Transmissíveis" y "IST" (con sus respectivas traducciones al inglés). Resultados: Seis artículos constituyeron la muestra final de este estudio. El diseño de investigación más prevalente fue el estudio transversal (n: 03). Se encontró que los factores asociados a la infección por VPH se relacionaron con características sociodemográficas (menor edad, baja escolaridad, estado civil soltero y consumo de alcohol durante el embarazo) y maternas (multiparidad). Conclusión: Se encontró que algunos factores pueden estar asociados a la presencia de infección por VPH en gestantes, como las características sociodemográficas y maternas. Es necesario que los profesionales de la salud tengan una mirada más cercana a este público, a fin de contribuir a la difusión de información y consecuente prevención.(AU)

Infecciones múltiples por Alphapapillomavirus, especie 9, en mujeres ecuatorianas con lesiones intraepiteliales y cáncer cervicouterino / Multiple infections by Alphapapillomavirus, specie 9, in Ecuadorian women with intraepithelial lesions and cervical cancer

Introducción: El significado biológico de las infecciones múltiples con virus del papiloma humano de alto riesgo oncogénico (VPH-AR), pertenecientes a la familia Alphapapillomavirus, en la carcinogénesis cervical aún es controversial. Objetivo: Proporcionar información sobre la circulación del VPH-AR del género Alphapapillomavirus-especie 9, e infecciones múltiples en mujeres ecuatorianas con lesiones intraepiteliales y cáncer cervicouterino (CaCU). Métodos: Se estudiaron 300 mujeres, residentes en la región Litoral del Ecuador. Se detectó la infección viral en muestras cervicales, mediante PCR anidada con cebadores genéricos MY09/11 y GP5/GP6. Los genotipos virales fueron identificados con el sistema comercial ANYPLEX II VPH28. La razón de prevalencia (RP) fue utilizada como medida de asociación entre las lesiones citológicas y las infecciones simples, múltiples o combinaciones de genotipos. Resultados: Se detectó VPH en el 92,00 % (276/300) de las mujeres, con frecuencias altas de infección por genotipos individuales, principalmente de alto riesgo oncogénico. Los VPH-AR más frecuentes fueron VPH58 (18,17 por ciento), 70 (8,64 por ciento), 53 (8,34 por ciento), 35 (7,45 por ciento), 16 (7,37 por ciento), 33 (6,55 por ciento), 31 (5,58 por ciento) y 18 (4,24 por ciento). En el 91,66 por ciento (253/276) de las muestras se detectaron infecciones múltiples, hasta con 13 tipos en una misma paciente, incluyendo varias especies del género Alphapapillomavirus. La combinación VPH16/VPH58 fue la más frecuente en lesiones de alto grado (RP = 2,9; p = 0,000), y la coinfección triple VPH16/VPH58/VPH70 predominó en las mujeres con CaCU (RP = 3,5; p = 0,007). Conclusión: Los resultados demuestran que la combinación VPH16/VPH58 del género Alphapapillomavirus, especie 9, podría ser un factor clave en la aparición de lesiones premalignas y su progresión hacia el CaCU(AU)

Introduction: It is still controversial the biological connotation of multiple infections with high-risk human papillomaviruses (hrHPV), that belong to the genus Alphapapillomavirus, for the cervical carcinogenesis. Objective: To provide information on the circulation of hrHPV, genus Alphapapillomavirus, specie 9, and the multiple infections in Ecuadorian women with intraepithelial lesions and cervical cancer. Methods: 300 women, from the coastal region of Ecuador, were screened. Viral infection was detected in cervix samples by nested PCR with MY09/11 and GP5/GP6 generic primers. Viral genotypes were identified using the commercial kit ANYPLEX II VPH28. The prevalence ratio (PR) was used to measure the association between cytological lesions and the simple, multiple or combined genotype infections. Results: Ninety-two percent of women (276/300) tested positive for HPV. Frequency of infection for single genotypes was high, mainly those of high oncogenic risk. The most frequent hrHPV genotypes were HPV58 (18.17 percent), 70 (8.64 percent), 53 (8.34 percent), 35 (7.45 percent), 16 (7.37 percent), 33 (6.55 percent), 31 (5.58 percent) and 18 (4.24 percent). In 91.66 percent (253/300) of the samples, multiple infections were detected, with up to 13 types in a single patient, including various species from the genus Alphapapillomavirus. The combination HPV16/HPV58 was the most frequent on high-grade lesions (PR = 2.9; p = 0,000), and HPV16/HPV58/HPV70 triple co-infection prevailed in women with cervical cancer (PR = 3.5; p = 0.007). Conclusions: The results evidence that the combination HPV16/HPV58, genus Alphapapillomavirus, specie 9, could be a key factor in the occurrence of premalignant lesions and their evolution into cervical cancer(AU)

Implementación del diagnóstico molecular del VPH: experiencia chilena en curso / Molecular diagnosis of human papillomavirus infection: the Chilean experience

Cervical Cancer (CaCu) has a heterogeneous epidemiological behavior throughout the planet, depending on regional socioeconomic development level. Some developed countries predict a potential eradication of this cancer in the next 100 years, while in Chile it still constitutes a pending challenge. Incidence rates show a slow but sustained downward prob, however, mortality has continued to fluctuate between 500-600 cases per year. A few years ago, vaccination against Human Papillomavirus (HPV), the main causal agent for this tumor, was consolidated as a public policy, both in girls and in boys. However, the technological leap in the screening prob was pending, from cytology to molecular diagnosis of the agent (HPV). In this report, we update our most recent data (2018) regarding CaCu mortality, then review global guidelines and experiences in HPV screening. Finally, we offer an account of the strategies that our health system is promoting to address the screening of the disease and whose molecular approach generates the widest worldwide scientific consensus. We also recognize the main barriers and future challenges, which, if overcome, would allow us to be in line with the mandate of WHO to control this women's health problema.

Screening of differentially expressed genes in CD4 + T cells in peripheral blood of 45 leprosy patients / 中华皮肤科杂志

Objective:To detect the mRNA expression profile of CD4 + T cells in the peripheral blood of leprosy patients, and to screen and identify genes that may be closely related to the pathogenesis of leprosy. Methods:From July 2018 to May 2020, 45 leprosy patients were collected from Hunan Province, and 45 healthy volunteers from Health Examination Center of Changsha Central Hospital. CD4 + T cells were isolated from peripheral blood samples by using magnetic beads, and then RNA was extracted. Solexa sequencing was performed to screen differentially expressed genes between 6 patients and 6 healthy controls, who were randomly selected from the above subjects. Differentially expressed genes were defined as those with a fold change greater than 2 and a P value below 0.05, and then Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was performed. Real-time fluorescence-based quantitative PCR was conducted to verify the gene expression. Results:Genetic screening revealed 4 831 newly-discovered transcripts with protein-coding potential. Eight differentially expressed genes were screened out between the two groups. Among them, the mRNA expression of CXCL8, PPBP, RPS18 and IL-1β genes was up-regulated, while the mRNA expression of RNH1, RPL39, RPL15 and AMBRA1 genes was down-regulated. Verification results of real-time fluorescence-based quantitative PCR were consistent with the above-mentioned genetic screening results. KEGG analysis showed that the differentially expressed genes between leprosy patients and healthy controls were mainly enriched in mitochondrial autophagy, autophagy-related pathways and human papillomavirus infection pathways.Conclusion:Down-regulated mRNA expression of AMBRA1 and RNH1 genes and up-regulated mRNA expression of CXCL8, PPBP and IL-1β genes were identified in patients with leprosy, which may be involved in the pathogenesis of leprosy through the mitochondrial autophagy pathway and chemokine-mediated signaling pathway, respectively.

Diagnostic value of quantitative detection of SLIT2 methylation for cervical high grade precancerous lesion / 天津医药

Objective To explore the clinical diagnostic value of quantitative detection of the slit homologue 2 (SLIT2) methylation for cervical high grade precancerous lesions. Methods According to histopathologic diagnostic results, 178 patients infected with high-risk HPV were divided into normal cervix group (n=45), low-grade lesion group (n=50) and high-grade lesion group (n=83). The cervical exfoliated cells were collected in three groups. The methylation levels of SLIT2 were measured by pyrosequencing in three groups. The diagnostic threshold of SLIT2 in high grade precancerous lesions was estimated by receiver operating characteristic (ROC) curve. Results The percentages of SLIT2 methylation were (4.53 ± 1.37)%, (5.81 ± 2.26)% and (11.80 ± 8.47)% in normal cervix group, low-grade lesion group and high-grade lesion group, respectively. And the differences between three groups were statistically significant (F=27.61, P<0.001). The percentage of SLIT2 methylation was significantly higher in high-grade lesion group than that of normal cervix group and low-grade lesion group (P<0.001). There was no significant difference in the percentage of SLIT2 methylation between normal cervix group and low-grade lesion group (P=0.297). The area under the ROC curve was 0.895 and optimal cut-off value was 6.41%. The sensitivity and specificity were 80.7% and 83.2%, respectively for the detection by SLIT2 methylation. Conclusion The quantitative detection of SLIT2 gene methylation level in cervical exfoliated cells by pyrosequencing can effectively diagnose cervical high grade precancerous lesions.

Effects of photodynamic therapy on the proliferation and apoptosis of human papillomavirus type 16 E7 proteinexpressing HaCaT cells / 中华皮肤科杂志

Objective To explore the effects of aminolevulinic acid-based photodynamic therapy (ALA-PDT) on the proliferation and apoptosis of HaCaT cells stably expressing human papillomavirus type 16 E7 protein (HaCaT/HPVl6 E7 cells).Methods Cultured HaCaT/HPV16 E7 cells were divided into several groups: blank control group receiving no treatment, ALA group treated with ALA alone, irradiation group irradiated with 630-nm red laser (30 mW/cm2,12 J/cm2), ALA-PDT groups pretreated with ALA for 5 hours followed by 630-nm red laser radiation at 4, 8, 12 J/cm2 respectively.CCK8 assay was performed to determine the survival rate of cells at 24 hours after PDT, and flow cytometetry and confocal microscopy were conducted to detect cell apoptosis and observe cell morphology respectively at 3 hours.Results At 24 hours, the survival rate of cells was 68.98％ ± 1.03％, 46.03％ ± 2.96％ and 23.57％ ± 3.83％ in the 4-,8-and 12-J/cm2 ALA-PDT groups respectively, significantly lower than that in the blank control group, ALA group and irradiation group (99.15％ ± 0.64％, 98.13％ ± 0.83％ and 96.85％ ± 1.37％ respectively, all P ＜ 0.05).With the increase in radiation dose, cell apoptosis was accelerated with obvious morphological changes and shrinkage of cells in the ALA-PDT groups.Conclusion ALA-PDT can inhibit the proliferation, and promote the apoptosis of HPV-infected HaCaT cells in a dose-dependent manner within a certain range of radiation dose.

Genotyping of human papillomavirus among human immunodeficiency virus-positive populations / 中华皮肤科杂志

Objective To compare the prevalence and genotype distribution of human papillomavirus (HPV) between human immunodeficiency virus (HIV)-positive and-negative populations.Methods Patients with condyloma acuminatum or persons who recently had sexual contact with patients with condyloma acuminatum were enrolled into this study,and classified into HIV-positive group (n =62) and HIV-negative group (n =2 716).GeneChip analysis was performed to detect HPV and determine HPV genotypes in mucocutaneous samples collected from the external genitalia of these subjects.Statistical analysis was carried out by chi-square test using the SPSS software version 19.0.Results The prevalence rates of HPV infection,high-risk HPV types and low-risk HPV types were significantly higher in HIV-positive persons than in HIV-negative persons (74.19％ (46/62) vs.42.30％ (1 149/2 716),67.74％ (42/62) vs.29.57％ (803/2 716),58.06％ (36/62) vs.24.71％ (671/2 716),respectively,all P＜ 0.01).The detection rate of HPV was also increased in HIV-positive men compared with HIV-negative men (92.11％ (35/38) vs.37.38％ (382/1 022),x2 =45.98,P ＜ 0.01).Although the top three genotypes of low-risk HPV were types 6,43 and 11 in both HIV-positive and-negative groups,the prevalence rate of HPV 6 was 37.10％ (23/62) in HIV-positive group,but only 11.12％ (302/2 716) in HIV-negative group.The top five genotypes of high-risk HPV were types 16 (22.58％,14/62),52,66,58 and 18 in HIV-positive group,and types 16 (7.77％,211/2716),58,56,66 and 52 in HIV-negative group.Coinfections with multiple HPV subtypes were common in both groups,and the number of concurrent HPV genotypes was as high as 8 in HIV-positive group,and 9 in HIV-negative group.The prevalence rate of coinfections with three or more HPV genotypes in HIV-positive group was significantly higher than that in HIV-negative group (65.21％ (30/46) vs.16.71％ (192/1 149)).Conclusions Compared with HIV-negative populations,HIV-positive populations show elevated prevalence of HPV infection,high-risk HPV genotypes and low-risk HPV genotypes.Moreover,the prevalence of HPV is higher in HIV-positive men than in HIV-negative men.These findings are worthy of further attention in clinic.

Expressions of zinc finger protein A20 and nuclear factor-κB in cutaneous squamous cell carcinoma tissue and their correlation with human papillomavirus infection / 中华皮肤科杂志

Objective To measure the expressions of zinc finger protein A20 and nuclear factor (NF)-κB in cutaneous squamous cell carcinoma (CSCC) tissue and their correlation with human papillomavirus (HPV) infection.Methods Tissue specimens were obtained from the lesions of 43 patients with CSCC and normal skin of 21 healthy human controls.Gene chips were used to detect the DNA of 21 HPV subtypes in these specimens.The expression levels of zinc finger protein A20 and NF-κB were determined by immunohistochemistry.The correlation between clinicopathological features of CSCC and HPV infection was estimated by Spearman rank correlation analysis.Results No significant difference was found in the expression level of either zinc finger protein A20 or NF-κB among patients of different age groups,gender,and with CSCC of different primary sites or histological grade (all P ＞ 0.05).However,there was a significant difference in the expression levels of zinc finger protein A20 and NF-κB between 39 patients with histological grade Ⅰ or Ⅱ and 4 patients with grade Ⅲ (25.85 ± 3.84 vs.48.34± 7.69 for zinc finger protein A20,46.64 ± 8.93 vs.57.34 ± 10.02 for NF-κB,both P ＜ 0.05),and between 3 patients with nodular metastasis and 40 patients without (35.34 ± 6.02 vs.26.51 ± 4.09 for zinc finger protein A20,57.53 ± 13.32 vs.45.45 ± 9.64 for NF-κB,P ＜ 0.05 or 0.01).The expression rate was 2/8,5/13 and 1/3 for zinc finger protein A20 (P ＞ 0.05),3/8,10/13 and 2/3 for NF-κB (P ＞ 0.05),in CSCC tissue specimens infected with low-risk HPV subtypes,high-risk subtypes,concurrent low-and high-risk HPV subtypes respectively.In HPV-infected CSCC tissue,a significantly positive correlation was found between the staining scores for zinc finger protein A20 and for NF-κB p65(r =3.14,P ＜ 0.05).Conclusion The high expressions of NF-κB and zinc finger protein A20 may play an important role in the oncogenesis of CSCC induced by HPV infection.

Correlation between polymorphisms at position 4 and 14 in exon 2 of the p73 gene and susceptibility to human papillomavirus infection / 中华皮肤科杂志

Objective To analyze the correlation between polymorphisms at position 4 and 14 in exon 2 of the p73 gene and susceptibility to human papillomavirus (HPV) infection.Methods Tissue specimens were obtained from the lesions of 83 patients with condyloma acuminatum and 11 patients with bowenoid papulosis,and blood samples from all the patients as well as 150 health checkup examinees with high risk for sexually transmitted diseases (STDs) at STD clinics (negative control group).PCR was performed to detect HPV DNA in lesional tissue specimens,followed by direct sequencing and nucleotide alignment using the BLAST program for the determination of HPV genotypes.To assess polymorphisms at position 4 and 14 in exon 2 of the p73 gene,DNA was extracted from all the blood samples,and the p73 gene was amplified by PCR with the primer shP73 followed by gene sequencing.The association between the polymorphisms and susceptibility to HPV infection was analyzed.Results Of the 83 tissue specimens from patients with condyloma acuminatum,42.2％ (35/83) were positive for HPV 6,and 41.0％ (34/83) for HPV 11.Among the 11 tisssue specimens from bowenoid papulosis lesions,5 were positive for HPV 16,and 3 for HPV 6.The p73 gene was successfully amplified and sequenced from all the patients with condyloma acuminatum or bowenoid papulosis as well as from 132 out of 150 health checkup examinees.There were three genotypes at position 4 and 14 in exon 2 of the p73 gene,including A4T14/G4C14,A4T14/A4T14,G4C14/G4C14,of which,A4T14/A4T14 was associated with a higher risk for condyloma acuminatum (OR 4.89,95％ CI 1.50-15.91) as well as bowenoid papulosis (OR 7.11,95％ CI 1.144-44.20),and G4C14/G4C14 with a lower risk for bowenoid papulosis (OR 0.16,95％ CI0.04-0.65),in patients with HPV infection.Conclusions The A4T14 allele in exon 2 of the p73 gene increases the risk for bowenoid papulosis and condyloma acuminatum,but no significant correlation is found between the susceptibility to high-or low-risk HPV infection and polymorphisms at the two positions in the p73 gene.

Association between hTERT Gene Amplification and High-Risk HPV Infection in Cervical Lesions / 天津医药

Objective To investigate the relationship between the amplification of human telomerase reverse tran-scriptase (hTERT) gene and high-risk human papillomavirus (HR-HPV) infections in cervical intraepithelial neoplasia (CIN) and cervical carcinoma. Methods The cervical epithelial cells were collected from 34 samples of normal cervical epithelium, 31 samples of CIN (gradeⅠ), 33 samples of CIN (gradeⅡ), 34 samples of CIN (gradeⅢ) and 20 samples of cer-vical carcinoma. HPV DNA was detected by polymerase chain reaction-reverse dot blot hybridization (PCR-RDB) and the amplification of hTERT gene was detected by fluorescence in situ hybridization (FISH). Results Twenty subtypes of HR-HPV were detected including HPV16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 73 and 82. The inci-dence of HR-HPV infection was higher in CINⅡgroup (72.73%), CINⅢgroup (85.29%) and cervical carcinoma group (90.00%) than that of normal cervical epithelium group (20.59%). There was no significant difference in the positive rate of HR-HPV DNA between CINⅠ group (54.84%) and normal cervical epithelium group (P < 0.005). The positive rate of hTERT gene amplification was higher in cervical carcinoma group (80.00%) than that of normal cervical epithelium group (0). There were no significant differences in the positive rates of hTERT gene amplification between CINⅠgroup ( 3.22%), CIN Ⅱ group (18.18%), cervical carcinoma group and CIN Ⅲ group (41.18%). There was positive correlation between hTERT gene amplification and HR-HPV infection (r=0.238, P<0.05). Conclusion The incidence of HR-HPV infection was positively correlated with hTERT gene amplification in cervical lesions. HR-HPV infection may be an early event of ab-normal amplification of hTERT gene. The detection of HPV-DNA and hTERT gene can be used in the clinical diagnosis of early cervical lesions.

Expressions of TLR7, MyD88 and TRAF6 in peripheral blood from patients with condyloma acuminatum / 中华皮肤科杂志

Objective To explore the role of Toll-like receptor 7 (TLR7) and related signal transduction molecules in mechanisms underlying human papilloma virus (HPV) infection and condyloma acuminatum (CA) recurrence.Methods Peripheral blood was obtained from 30 healthy controls,35 patients with primary CA,32 patiens with recurrent CA and 30 patients with recurrent CA treated by imiquimod and ALA-PDT.Two-color flow cytometric analysis was used to detect TLR7 expression in different peripheral blood T cell subsets,Western blot to determine the expression levels of an adapter protein myeloid differentiation primary response gene 88 (MyD88),and signaling molecules including tumor necrosis factor receptor-associated factor (TRAF6),phosphatidylinositol3-kinase (PI3K),protein kinase B (AKT),p42/44 and nuclear factor-kappa B (NF-κB) in peripheral blood CD3+ T cells,from these subjects.Statistical analysis was carried out by Student's t test using the software SPSS 13.0.Results TLR7 was expressed in peripheral blood CD3+CD4+ T cells and CD3+CD8+ T cells from the healthy controls.Compared with the healthy controls,the patients with primary and recurrent CA showed no significant changes in TLR7 expression in CD3+CD8+ T cells,but a statistical increase in TLR7 expression in CD3+CD4+ T cells (23.3％ ± 8.4％ and 32.8％ ± 8.9％ vs.12.6％ ± 6.3％,t =4.72,10.76,both P ＜ 0.01).Decreased expression of TLR7 in CD3+CD4+ T cells was observed in patients treated with imiquimod and ALAPDT compared with the patients with recurrent CA (20.3％ ± 5.7％ vs.32.8％ ±8.9％,t =5.41,P ＜ 0.01).The protein expressions of MyD88,TRAF6,PI3K,p42/44 and NF-κB were significantly increased in CD3 + T cells,while the AKT protein expression experienced no significant changes in patients with primary or recurrent CA compared with the healthy controls.A significant decrease was observed in the protein expression of MyD88,TRAF6,p42/44 and NF-κB in the treated patients compared with those with recurrent CA.Conclusions TLR7,which is highly expressed in peripheral blood CD3+CD4+ T cells in patients with CA,may take part in the host immune response against HPV and serve as a recognition receptor for HPV infection.