Prevalencia y genotipicación de virus papiloma humano vaginal y cervical en trabajadoras sexuales de un centro de salud sexual en la zona Norte de Santiago, Chile / Prevalence and genotypes of cervical and vaginal HPV in female sex workers attending a Sexual Control Centre, North Area of Santiago, Chile

INTRODUCCIÓN: En Chile, el cáncer de cuello uterino (CCU) es la segunda causa de muerte por neoplasias malignas en la mujer. El principal agente causal es el virus papiloma humano (VPH). Comparando con la población general, los o las trabajadoras(es) sexuales (TS) tienen alto riesgo de adquirir VPH. OBJETIVO: Analizar la prevalencia y genotipos del VPH cervical y vaginal en TS que se atienden en un Centro de Salud Sexual de Santiago, Chile. Pacientes y MÉTODO: Se realizó un estudio transversal en 97 mujeres TS, de 19 a 70 años de edad. Se obtuvieron dos muestras por paciente, una de exocérvix y otra de paredes vaginales. El ADN de VPH fue identificado por reacción de polimerasa en cadena (RPC) y su genotipo fue investigado para 32 tipos de VPH. RESULTADOS: La prevalencia de VPH global fue de 45%, observándose portación cervical en 41,2% y vaginal en 36,1%, con una coinfección de 32%. El 63% de las muestras tenía genotipos de alto riesgo. Los VPH de alto riesgo más frecuentes fueron el VPH 66 (12%), VPH 58 (9,3%), seguidos por VPH 16, VPH 59 y VPH 82 con igual frecuencia (8% c/u). Treinta y dos mujeres (43%) fueron infectadas con genotipos múltiples. CONCLUSIÓN: El VPH es una infección frecuente entre las TS. Este es el primer estudio en Chile sobre prevalencia y genotipos de VPH en TS.

BACKGROUND: In Chile, cervical cancer is the second leading cause of death from malignancy in women. The main causal agent of cervical cancer is the human papillomavirus (HPV). Compared with the general population, sex workers (SW) are at increased risk of acquiring HPV. AIM: To analyze the prevalence and genotypes of cervical and vaginal HPV in female SW attending a Sexual Control Centre. METHODS: A cross-sectional study was carried out on 97 women (19-70 years old). Two samples were taken per patient, one from exocervix and the other from vaginal walls. HPV DNA. was identified by polymerase chain reaction (PCR) and genotyping using specific probes for 32 types of HPV. RESULTS: The overall frequency of HPV was 45%, 41.2% in cervical carrier and 36.1% in vaginal carrier, 32% were co-infected, 63% of HPV were high-risk genotypes. The most frequent high-risk HPV was HPV 66 (12%), HPV 58 (9.3%), followed by HPV 16, HPV 59 and HPV 82 with the same frequency (8% each one). Thirty two (43%) of females were infected with multiple genotypes. CONCLUSION: HPV is frequent infection among SW. This is the first study in Chile on the prevalence and genotypes of HPV in sex workers.

Prevalence and frequencies of human papilloma virus types in adenocarcinoma in situ of the uterine cervix / 中华病理学杂志

Objective: To examine the prevalence and frequencies of human papillomavirus (HPV) genotypes in cervical adenocarcinoma in situ (AIS). Methods: The cases of cervical AIS with concurrent tests of cytology and HPV typing from January 2007 to February 2020 in the Obstetrics and Gynecology Hospital of Fudan University were collected and analyzed. Results: A total of 478 cases of cervical AIS were obtained. The average age of the patients was 39.4 years (range, 19-81 years). The largest age group was 30-39 years (44.8%), followed by 40-49 years (34.7%). Among the 478 patients, 355 underwent high-risk HPV (hrHPV) testing and had a hrHPV-positive rate of 93.8%. Of the 355 patients, 277 also underwent HPV typing and were mostly positive for either or both HPV16 and HPV18 (93.1%), with 55.6% positive for HPV18 and 48.7% positive for HPV16. Among the 478 cases, 266 cases (55.6%) were diagnosed with both AIS and squamous intraepithelial lesion (SIL), while 212 cases (44.4%) were diagnosed with only AIS. Patients infected with HPV16 in the AIS and SIL group significantly outnumbered those in the AIS alone group (P<0.05). Moreover, the rate of positive cytology was 55.9% (167/299 cases), while that of negative cytology was 44.1% (132/299). Among the 109 patients with negative cytology results and co-tested hrHPV, there were 101 HPV-positive cases (92.7%), of which 88 cases were subject to HPV typing and showed an HPV16/18 positive rate of 94.3% (83/88 cases). Conclusions: The combination of HPV typing and cytological screening can maximize the detection rate of cervical AIS, and should continue to be utilized, ideally on a larger scale, in the future.

Infection and distribution characteristics of HPV of middle-aged and elderly women from a certain hospital in Guangxi Zhuang Autonomous Region from 2018 to 2020 / 中华预防医学杂志

Objectives: To analyze the type and distribution characteristics of human papillomavirus (HPV) infection along with cervical cytology in middle-aged and elderly women in Guangxi and to provide a basis for the prevention and treatment of cervical cancer in elderly women. Methods: 21 subtypes of HPV and cervical cytology of women over 45-year-old visiting the First Affiliated Hospital of Guangxi Medical University from January 2019 to December 2020 were collected. They were divided into two groups by age, 45-64 years group and over 65 years group. The HPV, HR-HPV, and multiple HPV infection prevalence were analyzed, as well as HPV genotypes, the age distribution of HPV infection rate, and cervical cytology. Results: A total of 6 657 eligible women were included. 6 238 women were in the 45-64 years group, with a HPV prevalence about 20.86% (1 301), while 419 women were in the over 65 years group, with a HPV prevalence about 32.94% (138). The age-associated HPV and HR-HPV prevalence increased with the age, peaking at the age group of 70-74 years (P<0.001). The most prevalent genotype was HPV52, and the infection rate was 5.3% (353), followed by HPV16 and HPV 58, about 4.63% (308) and 3.08% (205) respectively. The majority cytology of HPV-positive middle-aged and elderly women was normal. 8.70% (88) of them were ASC-US, 6.52% (66) for HSIL, 4.55% (46) for LSIL, and 2.96% (30) for ASC-H, and 0.10% (1) for SCC. Compared to middle-aged women, elderly women had a lower negative cytology rate, 69.79% (67) vs. 77.95% (714), but a higher HSIL rate, 13.54% (13) vs. 5.79% (53) (P<0.05). Conclusions: HPV and HR-HPV prevalence of elderly women in a medical center of Guangxi are higher than those of middle-aged women. The most prevalent genotype is HPV16 in elderly women, followed by HPV52 and HPV58.

Human papillomavirus infection and oral squamous cell carcinoma - a systematic review / Infecção por papilomavírus humano e carcinoma espinocelular oral - Uma revisão sistemática

Abstract Introduction The association between uterine cervix and anogenital carcinomas and human papillomavirus, HPV, is well established, however the involvement of this virus in the development of oral squamous cell carcinomas remains controversial. Objectives To evaluate the relationship between HPV infection and oral squamous cell carcinomas, and to estimate the incidence of this infection in these patients. Methods Four electronic databases were searched to find studies that met the following inclusion criteria: i) performed in humans; ii) were cohort, case-control or cross-sectional; iii) assessed the HPV oncogenic activity by the E6 and E7 mRNA; iv) included primary oral squamous cell carcinomas which; v) diagnosis had been confirmed by biopsy. Information about the country; study period; sample obtainment; sites of oral squamous cell carcinomas; number, gender and age range of the population; the prevalence of HPV infection and subtypes detected; use of tobacco or alcohol and oral sex practice were extracted. The methodological quality of included articles was assessed using 14 criteria. Results The search strategy retrieved 2129 articles. Assessment of the full text was done for 626 articles, but five were included. The total of participants included was 383, most of them male with mean age between 51.0 and 63.5 years old. Seventeen patients were HPV/mRNA-positive, being the subtypes 16 and 18 detected more frequently. Nine of the HPV/mRNA-positive oral squamous cell carcinomas occurred on the tongue. The quality score average of included articles was five points. Conclusions Among the 383 oral squamous cell carcinoma patients included, 17 (4.4%) were HPV/mRNA-positive, nevertheless it was not possible to assess if HPV infection was associated with oral squamous cell carcinomas because none of the studies included was longitudinal and cross-sectional investigations do not have control group.

Resumo Introdução A associação entre os carcinomas de colo uterino e anogenitais e o papilomavírus humano (HPV) está bem estabelecida; entretanto, o envolvimento desse vírus no desenvolvimento de carcinomas espinocelulares orais permanece controverso. Objetivos Avaliar a relação entre a infecção pelo HPV e os carcinomas espinocelulares orais e estimar a proporção dessa infecção nesses pacientes. Método Quatro bases de dados eletrônicas foram pesquisadas para encontrar estudos que atendessem aos seguintes critérios de inclusão: i) feitos em humanos; ii) estudos do tipo coorte, caso-controle ou transversal; iii) avaliaram a atividade oncogênica do HPV pelo mRNA E6 e E7; iv) incluíram CECOs primários, cujo diagnóstico foi confirmado por biópsia; v) o diagnóstico foi confirmado por biópsia. Informações sobre o país; período do estudos; obtenção da amostra; locais dos carcinomas espinocelulares orais; número, sexo e faixa etária da população; prevalência de infecção por HPV e subtipos detectados; informações sobre o uso de tabaco ou álcool e a prática de sexo oral foram obtidas. A qualidade metodológica dos artigos incluídos foi avaliada através de 14 critérios. Resultados A estratégia de busca recuperou 2.129 artigos. A avaliação de texto completo foi feita em 626 artigos, mas apenas cinco foram incluídos. O total de participantes incluídos foi de 383, a maioria do sexo masculino e com média de idade entre 51,0 e 63,5 anos. Dezessete pacientes eram HPV/mRNA-positivos, os subtipos 16 e 18 foram detectados com maior frequência. Nove dos carcinomas espinocelulares orais HPV/mRNA-positivos ocorreram na língua. A média do escore de qualidade dos artigos incluídos foi de cinco pontos. Conclusões Entre os 383 pacientes incluídos com carcinomas espinocelulares orais, 17 (4,4%) eram HPV/mRNA-positivos; entretanto, não foi possível avaliar se a infecção por HPV estava associada com carcinomas espinocelulares orais porque nenhum dos estudos incluídos era longitudinal e as investigações transversais não têm grupo controle.

Optimización de unidades formadoras de colonias y detección del virus de papiloma humano en sangre de cordón umbilical / Colony-forming units optimization and human papillomavirus detection in umbilical cord blood

Resumen Introducción: Se requiere analizar diversos parámetros para el control de calidad adecuado de las unidades de sangre de cordón umbilical (USCU) cuando se utilizan con fines terapéuticos. Objetivo: Optimizar las unidades formadoras de colonias (UFC) de cultivos clonogénicos y detectar el genoma del virus del papiloma humano (VPH) en USCU. Métodos: Se incluyeron 141 muestras de sangre de cordón umbilical (SCU), de segmento y de UFC de cultivos clonogénicos de USCU. Se realizó extracción de ADN, cuantificación y amplificación por PCR del gen endógeno GAPDH. Se detectó el gen L1 del VPH con los oligonucleótidos MY09/MY11 y GP5/GP6+; los productos de PCR se migraron en electroforesis de agarosa. El ADN purificado de las UFC se analizó mediante electroforesis de agarosa y algunos ADN, con la técnica sequence specific priming. Resultados: La concentración de ADN extraído de UFC fue superior comparada con la de SCU (p = 0.0041) y la de segmento (p < 0.0001); así como la de SCU comparada con la de segmento (p < 0.0001). Todas las muestras fueron positivas para la amplificación de GAPDH y negativas para MY09/MY11 y GP5/GP6+. Conclusiones: Las USCU criopreservadas fueron VPH netativas; además, es factible obtener ADN en altas concentraciones y con alta pureza a partir de UFC de los cultivos clonogénicos.

Abstract Introduction: Analysis of several markers is required for adequate quality control in umbilical cord blood units (UCBU) when are used for therapeutic purposes. Objective: To optimize colony-forming units (CFU) from clonogenic cultures and to detect the human papillomavirus (HPV) genome in UCBU. Methods: One hundred and forty-one umbilical cord blood (UCB), segment or CFU samples from UCBU clonogenic cultures were included. DNA extraction, quantification and endogenous GAPDH gene PCR amplification were carried out. Subsequently, HPV L1 gene was detected using the MY09/MY11 and GP5/GP6+ oligonucleotides. PCR products were analyzed with electrophoresis in agarose gel. CFU-extracted purified DNA was analyzed by electrophoresis in agarose gel, as well as some DNAs, using the SSP technique. Results: CFU-extracted DNA concentration was higher in comparison with that of UCB (p = 0.0041) and that of the segment (p < 0.0001), as well as that of UCB in comparison with that of the segment (p < 0.0001). All samples were positive for GAPDH amplification and negative for MY09/MY11 and GP5/GP6+. Conclusions: Cryopreserved UCBUs were HPV-negative. Obtaining CFU DNA from clonogenic cultures with high concentrations and purity is feasible.

Virus del papiloma humano en carcinoma colorrectal / Human papilloma virus in colorectal carcinoma

Resumen Introducción: Previos trabajos han reportado una asociación entre la infección del virus del papiloma humano (VPH) y el desarrollo de cáncer colorrectal, aunque existe controversia al respecto. Materiales y Método: Estudio observacional, transversal, descriptivo, retrospectivo, no ciego. Se utilizaron 50 muestras de patología con diagnóstico de adenocarcinoma colorrectal, incluidas en parafina, para aislar ADN de las muestras. Se realizó la extracción de ADN mediante protocolos establecidos para extracción, lisis y rehidratación de muestra. Se identificó y genotipicó el ADN del virus para amplificar y detectar subtipos oncogénicos de entre 35 subtipos diferentes incluidos en la prueba, secuenciando las muestras positivas, utilizando protocolos ya establecidos de purificación y análisis de muestra, mediante microarreglos. Resultados: Se identificaron 14 muestras de 50 (28%) estudiadas positivas para el virus de papiloma humano de las cuales 11 (22%) incluyen uno o más subtipos de alto riesgo para neoplasia. No se identificaron diferencias estadísticamente significativas entre grupos en cuanto a edad, sexo, localización del tumor, grado de diferenciación, infiltración, ganglios afectados, metástasis o número de paquetes/año. Conclusión: La detección de los subtipos de VPH de alto riesgo en un alto porcentaje de las muestras positivas, sugiere una asociación entre la infección con el desarrollo de cáncer colorrectal.

Introduction: Previous works have reported an association between human papilloma virus (HPV) infection and the development of colorectal cancer, and although controversy regarding this association exists. Materials and Method: This was an observational, cross-sectional, descriptive, retrospective unblinded study. Fifty pathology samples embedded in paraffin with a diagnosis of colorectal adenocarcinoma were used to isolate DNA from the tissue. DNA was extracted according to established protocols for extraction, lysis and sample rehydration. Viral DNA was identified and genotypified to amplify and detect oncogenic subtypes among 35 different subtypes included in the study, sequencing positive samples with established protocols of purification and sample analysis using microarrays. Results: Fourteen of 50 (28%) samples were identified as positive for human papilloma virus; of these 11 (22%) included one or more high-risk subtypes for neoplasia. Statistically significant differences were not found between the groups regarding age, sex, tumor location, degree of differentiation, infiltration, affected lymph nodes, metastasis and number of pack years. Conclusion: The detection of high-risk VPH subtypes in a high percentage of positive samples, suggests an association between infection and the development of colorectal cancer.

Human papillomavirus distribution and cervical cancer epidemiological characteristics in rural population of Xinjiang, China / 中华医学杂志(英文版)

BACKGROUND@#Cervical cancer remains a major public health issue for the Uyghur women and other women living mainly in rural areas of Xinjiang. This study aims to investigate the distribution of human papillomavirus (HPV) infection and cervical cancer in rural areas of Xinjiang, China.@*METHODS@#Cervical cancer screening was performed on rural women aged 35 to 64 years from Xinjiang, China in 2017 through gynecological examination, vaginal discharge smear microscopy, cytology, and HPV testing. If necessary, colposcopy and biopsy were performed on women with suspicious or abnormal screening results.@*RESULTS@#Of the 216,754 women screened, 15,518 received HPV testing. The HPV-positive rate was 6.75% (1047/15,518). Compared with the age 35-44 years group, the odds ratios (ORs) of HPV positivity in the age 45-54 years and 55-64 years groups were 1.18 (95% confidence interval [CI]: 1.02-1.37) and 1.84 (95% CI: 1.53-2.21), respectively. Compared with women with primary or lower education level, the ORs for HPV infection rates of women with high school and college education or above were 1.37 (95% CI: 1.09-1.72) and 1.62 (95% CI: 1.23-2.12), respectively. Uyghur women were less likely to have HPV infection than Han women, with an OR (95% CI) of 0.78 (0.61-0.99). The most prevalent HPV types among Xinjiang women were HPV 16 (24.00%), HPV 33 (12.70%), and HPV 52 (11.80%). The detection rate of cervical intraepithelial neoplasia (CIN)2+ was 0.14% and the early diagnosis rate of cervical cancer was 85.91%. The detection rates of vaginitis and cervicitis were 19.28% and 21.32%, respectively.@*CONCLUSIONS@#The HPV infection rate in Xinjiang is low, but the detection rate of cervical cancer and precancerous lesions is higher than the national average level. Cervical cancer is a prominent public health problem in Xinjiang, especially in southern Xinjiang.

Características operativas de técnicas moleculares empleadas para la detección del virus del papiloma humano en el proyecto ESTAMPA / Operational characteristics of molecular techniques used to detect human papillomavirus in the ESTAMPA project

Resumen El desarrollo y la innovación de nuevas tecnologías ha permitido mejorar la detección de la infección por el virus del papiloma humano de alto riesgo. La captura de híbridos II es un ensayo que se basa en hibridación y quimioluminiscencia. Cobas VPH Test es una PCR cualitativa y Aptima VPH Assay permite detectar la expresión de ARN mensajero de las oncoproteínas E6/E7 del VPH de alto riesgo. Estas técnicas presentan ventajas en comparación con la citología convencional, que se utiliza como prueba de rutina para la detección temprana del cáncer de cuello uterino. En el estudio ESTAMPA se realizaron 13.691 procesamientos que permitieron identificar que para el planteamiento de proyectos de investigación o para la implementación de pruebas de tamizaje de VPH es necesario analizar las ventajas y desventajas de las pruebas del mercado.

Abstract The development and innovation of new technologies has improved the detection of high-risk human papillomavirus infection. Hybrid capture II is an assay that is based on hybridization and chemiluminescence. Cobas HPV Test is a qualitative PCR and Aptima HPV Assay allows to detect the expression of messenger RNA of the high- risk HPV E6 / E7 oncoproteins. These techniques have advantages, in comparison, with conventional cytology that is routinely used for the detection of cervical cancer. In the ESTAMPA study, 13,691 prosecutions were carried out that allowed to identify that for the planning of research projects or for the implementation of HPV screening tests, it is necessary to analyze the advantages and disadvantages of market tests.

Teste de micronúcleo para detecção de instabilidade genômica em lesão cervical por papilomavírus humano / Prueba de micronúcleo para detectar inestabilidad genómica en lesión cervical por virus del papiloma humano / Micronucleus test to detect genomic instability in cervical lesion by human papillomavirus

Objetivo: analisar a produção científica acerca do teste de micronúcleo como instrumento para detecção de instabilidade genômica e dos fatores de risco para lesão intraepitelial cervical em pacientes com papilomavírus humano. Método: revisão integrativa de publicações dos últimos 10 anos, realizada no período de agosto de 2017 a junho de 2018, através da Medical Literature Analysis and Retrieval System, Literatura Latino-americana e do Caribe em Ciências da Saúde e PubMed Central. Resultados: quatro artigos foram analisados em que o teste de micronúcleo foi utilizado para detectar instabilidade genômica e risco de lesão intraepitelial cervical e seis artigos como biomarcador em diferentes estágios pré-neoplásicos, neoplásicos em lesões intraepiteliais e fatores de risco para o câncer cervical. Conclusões: o teste de micronúcleo é um método simples, rápido, barato e importante para detectar instabilidade genômica em células intraepiteliais cervicais que apresentam lesão sugestiva para o câncer de colo uterino.(AU)

Objective: to analyze the scientific production about the micronucleus test as an instrument for detecting genomic instability and risk factors for cervical intraepithelial injury in patients with human papillomavirus. Method: integrative review of publications from the last 10 years, carried out from August 2017 to June 2018, through Medical Literature Analysis and Retrieval System, Latin American and Caribbean Literature in Health Sciences and PubMed Central. Results: four articles were analyzed in which the micronucleus test was used to detect genomic instability and risk of cervical intraepithelial injury and in six articles as a biomarker in different pre-neoplastic stages, neoplastic in intraepithelial injuries and risk factors for cervical cancer. Conclusions: the micronucleus test is a simple, fast, inexpensive and important method to detect genomic instability in cervical intraepithelial cells that present lesions suggestive of cervical cancer.(AU)

Objetivo: analizar la producción científica sobre la prueba de micronúcleos como instrumento para detectar la inestabilidad genómica y los factores de riesgo de lesión intraepitelial cervical en pacientes con virus del papiloma humano. Método: revisión integradora de publicaciones de los últimos 10 años, realizada desde agosto de 2017 hasta junio de 2018, a través de la Medical Literature Analysis and Retrieval System, Literatura Latinoamericana y del Caribe en Ciencias de la Salud y PubMed Central. Resultados: se analizaron cuatro artículos en los que se utilizó la prueba de micronúcleos para detectar la inestabilidad genómica y el riesgo de lesión intraepitelial cervical y en seis artículos como biomarcador en diferentes etapas preneoplásicas, neoplásico en lesiones intraepiteliales y factores de riesgo de cáncer cervical. Conclusiones: la prueba de micronúcleos es un método simple, rápido, económico e importante para detectar la inestabilidad genómica en células intraepiteliales cervicales que presentan lesiones sugestivas de cáncer cervical.(AU)

Comparison between anal cytology, high-resolution anoscopy and HPV DNA genotyping by polymerase chain reaction in the post-treatment follow-up of condylomata acuminata / Comparação entre citologia anal, colposcopia anal e genotipagem do HPV por reação em cadeia da polimerase no seguimento pós-operatório de condiloma acuminado

ABSTRACT Aim: to evaluate the presence of subclinical HPV-induced anal lesions with anal cytology, High-Resolution Anoscopy (HRA) and HPV genotyping by polymerase chain reaction (PCR) in the follow-up of treated condylomata acuminata (CA). Methods: seventy-nine male patients were included. One month after anal CA eradication, the patients underwent brush samples collection for anal cytology and PCR, and HRA with biopsy of acetowhite lesions. These methods were compared within all patients and between groups, according to Human Immunodeficiency Virus (HIV) infection status: HIV-negative; HIV-positive with TCD4 count above and below 350 cells/mm3. Results: the most frequent HPV types were 6 and 16. HPV DNA was isolated in 92%. HIV infection was associated with a higher number of oncogenic HPV types (p=0.038). All patients with negative PCR had negative HRA and cytology. There were no differences in cytological, HRA or histopathological findings between groups. Conclusion: the association of the findings of cytopathology, HRA and genotyping of HPV refined the diagnosis of HPV-induced lesions. The degree of immunodeficiency was not associated with increase in remnant HPV-induced anal lesions.

RESUMO Objetivo: avaliar a presença de lesões anais subclínicas HPV-induzidas com citologia anal, colposcopia anal e genotipagem de HPV por reação em cadeia da polimerase (PCR) no seguimento de condilomas anais tratados. Método: foram incluídos 79 pacientes do sexo masculino. Após um mês da erradicação de lesões condilomatosas anais, os participantes voltaram em consulta para coleta de amostras com escova para citologia anal e PCR, e colposcopia anal com biópsia de lesões acetobrancas. Os métodos de detecção das lesões foram comparados entre os pacientes e entre grupos, de acordo com o status de infecção pelo vírus da imunodeficiência humana (HIV): HIV-negativo; HIV-positivo com TCD4 acima ou abaixo de 350 células/mm3. Resultados: os tipos de HPV mais frequentes foram 6 e 16. Infecção pelo HIV foi associada a maior número de tipos de HPV oncogênicos (p=0,038). Todos os pacientes com PCR negativo apresentaram colposcopia e citologia negativos. Não houve diferença nos achados citológico, colposcópico ou histopatológico entre grupos. Conclusão: a associação dos achados citopatológico, colposcópico e PCR melhorou a acurácia do diagnóstico de lesões anais HPV-induzidas. O grau de imunodeficiência não foi associado a maior frequência de lesões anais HPV-induzidas remanescentes.

Human papillomavirus infection in men with condyloma acuminatum: Genotype analysis of 70 cases / 中华男科学杂志

Objective@#To investigate the distribution of the gene subtypes of human papillomavirus (HPV) in male patients with condyloma acuminatum (CA) and analyze the characteristics of the gene subtypes.@*METHODS@#We extracted genomic DNA of the HPV virus from the genital tissue of 70 male CA patients, detected the DNA subtypes of HPV using the PCR-reverse dot hybridization technique, and analyzed the rates of different subtypes identified and their characteristics of distribution in different age groups.@*RESULTS@#The male HPV-positive patients were mainly infected at the age of 20－39 years, primarily with high- and low-risk mixed infection of various subtypes, which accounted for 61.54% in the 20- to 29-year-olds and 42.86% in the 30- to 39-year-olds. Among the 70 CA patients, 22 HPV subtypes were identified, the top five subtypes including HPV 11 (21.08%), HPV 6 (19.46%), HPV 42 (6.49%), HPV 59 (6.49%) and HPV 53 (5.95%); 20 infected with a single subtype (28.57%), 19 with two subtypes (27.14%) and 31 with three or more (44.29%); and 30 infected with a low-risk single subtype (42.86%) and 40 with both high- and low-risk multiple subtypes (57.14%).@*CONCLUSIONS@#Male patients with CA are mainly infected with HPV 11 and HPV 6, with a significantly higher rate of multi-subtype than single-subtype infection, and the multi-subtype patients chiefly with high- and low-risk mixed infection. Men aged 20－39 years old are most commonly affected by CA.

Human papillomavirus and risk factors for cervical adenocarcinoma in the state of Pernambuco, Brazil / Papilomavírus humano e fatores de risco para adenocarcinoma cervical no estado de Pernambuco, Brasil

Abstract Objectives: to determine the incidence of the main high oncogenic risk types of the human papillomavirus (HPV) ( 16, 18, 31 and 33) and the risk factors for cervical adenocarcinoma. Methods: a case-control study was carried out with 324 women (69 with adenocarcinoma and 260 healthy controls) between 2001 and 2014. Information on risk factors associated with adenocarcinomawere collected and the detection performed on HPVby using Polymerase Chain Reaction (PCR) method. Results: adenocarcinoma was associated with age ≥40 years old (OR=2.95; 95%CI=1.13-7.71), ≤3 years of schooling (OR=2.34; 95%CI=1.02-5.37), presence of HPV (OR=6.75; 95%CI=2.41-18.91),women in menopausal status (OR=4.76; 95%CI:1.70-13.31) black race (OR=6.71; 95%CI= 2.11-21.32) and never had undergone cervical cancer screening (OR=9.92; 95%CI:2.41-40.81). Andamong the HPV types detected, HPV 18 was observed to be strongly associated with adenocarcinoma of the cervix (OR=99.1; 95%CI=12.96-757.78). Conclusions: the factors associated with cervical adenocarcinoma were ≥40 years old, ≤3 years of schooling, black race, menopausal status, never had undergone cervical cancer screening and the presence of HPV.

Resumo Objetivos: determinar a incidência dos principais Papilomavirus Humano (HPV) de alto risco oncogênico (16, 18, 31 e 33) e os fatores associados ao adenocarcinoma do colo uterino. Métodos: realizado estudo de caso-controle com 324 mulheres (69 com adenocarcinoma e 260 controles saudáveis), de 2001 a 2014. Foram colhidas informações sobre fatores de risco associados ao adenocarcinoma e realizada a detecção do HPV pelo método da Reação em Cadeia da Polimerase (PCR). Resultados: o adenocarcinoma foi associado à idade >40 anos (OR=2,95; IC95%=1,13 - 7,71), escolaridade <3 anos (OR=2,34; IC95%=1,02 - 5,37), presença do HPV (OR=6,75; IC95%=2,41 - 18,91), mulher no estado menopausal (OR=4,76; IC 95%=1,70 - 13,31), raça negra (OR=6,71; IC95%=2,11 - 21,32) e nunca ter feito o exame de prevenção de Papanicolau (OR=9,92; IC95%=2,41 - 40,81). Entre os tipos de HPV encontrados observou-se que HPV 18 teve forte associação (OR=99,1; IC95%=12,96 - 757,78) com o adenocarcinoma de colo uterino. Conclusões: os fatores associados ao adenocarcinoma de colo uterino foram idade >40 anos, escolaridade <3 anos, raça negra, estado menopausal, nunca ter realizado o Papanicolau e presença do HPV.

Frecuencia de alteraciones citológicas cervicales y virus papiloma humano en una muestra de estudiantes universitarias en Temuco, Chile / Frequency of cervical cytological alterations and human papilloma virus in a sample of university students in Temuco, Chile

Resumen Introducción: El inicio precoz de actividad sexual puede favorecer el desarrollo de alteraciones cervicales y de infecciones de transmisión sexual, en especial del virus papiloma humano (VPH) muy frecuente en adolescentes y jóvenes. Objetivo: Analizar el estado del cuello uterino, presencia del VPH y conductas sexuales en mujeres menores de 25 años. Material y Métodos: Participaron 182 estudiantes universitarias de 18-24 años, sanas, sexualmente activas y no vacunadas para VPH. Se realizó Papanicolaou (Pap) y clasificación del VPH en alto y bajo riesgo (AR y BR) mediante reacción de polimerasa en cadena en tiempo real. Las conductas sexuales fueron consultadas privadamente. Resultados: El 46,9% de los Pap presentaron alteraciones citológicas (inflamación inespecífica/hemorrágico: 29,4% y frotis atípicos (FA):10,2%). La frecuencia de los VPH-AR fue 24,3%; de éstos, 67,4% presentó un Pap alterado. Hubo asociación entre alteraciones citológicas y presencia de VPH (p < 0,0001) y años de actividad sexual y FA o neoplasia intraepitelial grado I (NIE I) (p = 0,009). El 11,9% de las jóvenes estudiadas (21/177) presentó FA o NIE I, con 66,7% de casos VPH-AR. Conclusiones: Estos hallazgos alertan la vulnerabilidad de estas jóvenes que tendrían un riesgo potencial de persistencia viral, NIE y eventualmente cáncer. Es importante enfatizar consejería y prevención previo a la edad normada de ingreso al programa de cribado para cáncer cérvico uterino en Chile.

Background: The early onset of sexual activity can promote the development of cervical alterations and sexually transmitted infections, especially the human papillomavirus (HPV) very common in adolescents and young people. Aim: The condition of the cervix, HPV and sexual behavior in young women under 25 years of age were analyzed. Methods: 182 university students, healthy, sexually active, 18-24 years old, without vaccine for HPV participated. Papanicolaou (Pap) test and classification of high and low risk HPV (HR and LR) were performed by real time polymerase chain reaction. The sexual behaviors were consulted in private. Results: The 46.9% of Pap presented cytological alterations, non-specific inflammation/hemorrhagic (29.4%) and atypical smear (10.2%) being de most frequent. The overall frequency of HPV-HR was 24.3%, of these 67.4% presented an altered Pap. There was an association between cytological alterations and HPV (p < 0.0001) and years of sexual activity and atypical smear or cervical intraepithelial neoplasia grade I (CIN I) (p = 0.009). 11.9% of young women (21/177) presented atypical smear or CIN I, with 66.7% of cases HPV-HR. Conclusions: These findings alert the vulnerability of these young women who would have a potential risk of viral persistence, CIN and eventually cancer. It is important to emphasize counseling and prevention prior to the regular age of admission to the screening program for cervical cancer. This study was financed by the Universidad de La Frontera through Projects DI15-0047 and DI17-0123.

Genotipificación de VPH en papilomas orales de pacientes con infección por VIH del Hospital San Juan de Dios / HPV genotypes in oral papilloma in Hospital San Juan de Dios HIV (+) patients

Resumen Introducción: Pacientes con infección por VIH presentan mayor riesgo de infecciones orales con genotipos de virus papiloma humano (VPH) de alto riesgo oncogénico (VPH-AR). Objetivo: Determinar los genotipos de VPH en lesiones papilomatosas orales de pacientes con infección por VIH y describir los factores clínicos, histopatológicos y recuento de linfocitos T CD4+ y carga viral asociados. Métodos: Se estudiaron ocho sujetos adultos con infección por VIH y lesiones papilomatosas por VPH. Se extrajo el ADN de la lesión y se detectó el genoma y los genotipos de VPH mediante reacción de polimerasa en cadena e hibridación con el kit comercial HPV 3.5 LCD-Array (Chipron®) y se describieron factores asociados. Resultados: El 63% de los pacientes exhibió más de un genotipo de VPH y 75% de ellos exhibió al menos un genotipo VPH-AR. El genotipo más frecuente fue el VPH 52 (27%), seguido del VPH16 y 56 (18%). El recuento medio de linfocitos T CD4+ en pacientes con al menos un genotipo VPH-AR fue de 330,6 céls/mm3. Conclusiones: Se detectó una mayor frecuencia de infecciones múltiples por VPH, incluido al menos un genotipo de alto riesgo. El genotipo VPH-AR 52 fue el más frecuente. El recuento medio de LT CD4+ en pacientes que presentan al menos un genotipo VPH-AR indica una inmunosupresión moderada. Se requiere aumentar el número de pacientes.

Background: HIV (+) patients have a higher risk of oral infections with high oncogenic risk HPV (HPV-HR). Aim: To determine the HPV genotypes in oral papillomatous lesions in HIV (+) patients and describe the associated factors. Methods: Eight adults HIV (+) subjects with papillomatous HPV lesions were studied. The lesions DNA was extracted and HPV genome and genotypes were detected by PCR and the commercial kit HPV 3.5 LCD-Array Kit (Chipron®) and associated factors were described. Results: 63% of patients exhibited more than one HPV genotype and 75% of them exhibited at least 1 HPV-HR genotype. The most frequent genotype was HPV 52 (27%), followed by HPV 16 and 56 (18%). The mean CD4 T lymphocyte count in patients with at least one HPV-HR genotype was 330.6 cells/mm3. Conclusions: A higher frequency of multiple HPV infections was detected, including at least one high-risk genotype. The genotype HPV-AR 52 was the most frequent. The mean CD4 T lymphocyte count in patients with at least one HPV-HR genotype indicates moderate immunosuppression. It is required to increase the number of patients.

Detección y tipificación del Virus Papiloma Humano en el marco del tamizaje virológico para la detección de lesiones del cuello uterino en Asunción, Paraguay / Detection and typing of Human Papilloma Virus during a virological screening for detection of cervical lesions in Asunción, Paraguay

En Paraguay la incidencia de cáncer de cuello uterino (CCU) es superior a las observadas en otros países de la región. El agente etiológico asociado al CCU es el virus papiloma humano (VPH), esencialmente tipos de alto riesgo oncogénicos. El objetivo es describir aspectos epidemiológicos de la infección genital por el virus papiloma humano de alto riesgo (VPH-AR) en mujeres de 25 a 64 años que consultaron en servicios de Patología Cervical del MSPyBS, de mayo a diciembre de 2013. Se utilizó el Cobas 4800 HPV Test (Roche) que permite la detección individual de VPH-16 y VPH-18 y un pool de otros VPH-AR que incluye 12 genotipos de alto riesgo. Los otros VPH-AR fueron tipificados por hibridación reversa en línea (RLB). Entre las 495 mujeres incluidas, se detectaron 72 casos positivos (14,5%) de VPH-AR. Se identificaron 19 tipos virales; siendo el más frecuente VPH-16 (2,1%), seguido del VPH-31, 33, 58 y 66; el VPH-18 aparece en sexto lugar. Este trabajo aporta los primeros datos sobre la implementación de técnicas moleculares para detección y tipificación de VPH como parte del sistema de salud pública de Paraguay. El predominio de VPH-16, confirma su amplia circulación a nivel mundial y dado su mayor potencial oncogénico, representa una alerta a considerar, en especial en las mujeres mayores de 30 años portadoras de una infección persistente. Estos resultados apoyan la importancia de la implementación criteriosa y la utilización apropiada de las pruebas moleculares actualmente disponibles para la prevención y control del CCU(AU)

¿Permiten la citología, el genotipado y la anoscopia de alta resolución establecer un protocolo para la detección precoz del carcinoma epidermoide de canal anal en población de riesgo? / Do cytology, genotyping, and high resolution anoscopy allow to establish a protocol for early detection of squamous cell carcinoma of the anal canal in risk population?

Introducción: El cáncer anal ha experimentado un aumento de incidencia en los últimos años. Está mediado por el VPH y precedido de cambios precancerosos planteando la posibilidad de dirigir los esfuerzos preventivos hacia los grupos de alto riesgo. Sigue siendo controvertida la indicación de cribado y los métodos de detección ideales. Objetivo: Validar las pruebas de cribado implementadas en la actualidad comparadas con la biopsia como "gold standard". Material y Métodos: Estudio transversal con recogida de datos prospectiva, en una cohorte de hombres VIH+ que tienen sexo con hombres, pertenecientes al Hospital Gregorio Marañón e Infanta Leonor en un periodo de 2 años. Resultados: Se seleccionaron 179 pacientes con 286 visitas a la consulta de screening en las que se llevaron a cabo 3 pruebas de cribado en paralelo (citología anal, genotipado del VPH y anoscopia de alta resolución (AAR) con toma de biopsia dirigida sobre zona sospechosa o aleatoria). La sensibilidad y especificidad para la detección de displasia de alto grado y cáncer y su grado de concordancia con la biopsia fue la siguiente: citología 3,23%/94,43% (k: 0,03), genotipado de VPH de alto riesgo 90,32%/27,45% (k: 0,05), AAR 32,26%/87,45 (k: 0, 17) siendo el rendimiento diagnóstico de las tres pruebas muy bajo. Conclusión: La citología presenta un rendimiento diagnóstico muy bajo comparado con el genotipado que representa el mayor. A la luz de nuestros resultados, los protocolos clínicos tal y como vienen desarrollándose en la actualidad deberían de ser abandonados.

Introduction: The incidence of anal cancer has increased in recent years. It is mediated by HPV and preceded by precancerous changes, raising the possibility of directing preventive efforts towards high-risk groups. The indication of screening remains controversial and which methods would be the ideal ones. Objective: To validate the screening tests established actually, comparing it with the biopsy considered as the "gold standard". Materials and Methods: A cross-sectional study was performed, with prospective data collection in a cohort of VIH+ patients, who have male homosexual anal relations, belonging to Gregorio Marañón and Infanta Leonor Hospitals in a period of 2 years. Results: A total of 179 patients were selected with 286 visits to the screening Outpatient Clinic in which 3 parallel screening tests were performed (anal cytology, HPV genotyping and high resolution anoscopy (AAR) with a biopsy directed on a suspicious or random area). The sensitivity and specificity for the detection of high-grade dysplasia and cancer and their degree of agreement with the biopsy was as follows: cytology 3.23%/94.43% (k: 0.03), high HPV genotyping. risk 90.32%/27.45% (k: 0.05), AAR 32.26%/87.45 (k: 0, 17), the diagnostic accuracy of the three tests being very low. Conclusion: Cytology shows a very low diagnostic accuracy compared to the genotype that represents the highest one. In light of our results, clinical protocols as they are currently being developed should be abandoned.

Detección del virus del papiloma humano en muestras obtenidas mediante técnica de autotoma en un grupo de universitarias peruanas / Detection of the human papillomavirus in samples obtained by self-collection technique in a group of peruvian college students

RESUMEN Estudio transversal que determinó la frecuencia y genotipos del virus del papiloma humano de alto riesgo (VPH-AR) a través de la técnica de autotoma en un grupo de universitarias de Lima. Participaron 221 estudiantes y se detectó el ADN del VPH-AR con el método de reacción en cadena de la polimerasa (PCR). La frecuencia del VPH-AR en las participantes fue de 43,4%; de este grupo se encontraron los genotipos VPH 16 en el 15,6% y VPH 18 en el 4,2% y otros VPH-AR en el 80,2%. Se concluye que la frecuencia del VPH-AR es mayor en el grupo de universitarias de este estudio en comparación a investigaciones nacionales previas.

ABSTRACT Cross-sectional study that determined the frequency and the genotypes of the (HR-HPV) high-risk human papillomavirus through the self-collection technique in a group of college students of Lima. Two hundred twenty-one (221) students participated and the DNA of the HR-HPV was detected with polymerase chain reaction (PCR). The frequency of HR-HPV in participants was 43.4%; of this group, genotype HPV 16 was present in 15.6%, HPV 18 in 4.2%, and another HR-HPV in 80.2%. We can conclude that the frequency of HR-HPV is greater in the group of college students of this study in comparison with previous national investigations.

PCR-RFLP assay as an option for primary HPV test

Persistent human papillomavirus (HPV) infection is an essential factor of cervical cancer. This study evaluated the analytical performance of restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) assay compared to PapilloCheck® microarray to identify human papilloma virus (HPV) in cervical cells. Three hundred and twenty-five women were analyzed. One sample was used for conventional cytology and another sample was collected using BD SurePath™ kit for HPV tests. Eighty samples (24.6%) were positive for HPV gene by PCR-Multiplex and were then submitted to PCR-RFLP and PapilloCheck® microarray. There was a genotyping agreement in 71.25% (57/80) on at least one HPV type between PCR-RFLP and PapilloCheck® microarray. In 22 samples (27.5%), the results were discordant and those samples were additionally analyzed by DNA sequencing. HPV 16 was the most prevalent HPV type found in both methods, followed by HPVs 53, 68, 18, 39, and 66 using PCR-RFLP analysis, and HPVs 39, 53, 68, 56, 31, and 66 using PapilloCheck® microarray. In the present study, a perfect agreement using Cohen's kappa (κ) was found in HPV 33 and 58 (κ=1), very good for HPV 51, and good for types 16, 18, 53, 59, 66, 68, 70, and 73. PCR-RFLP analysis identified only 25% (20/80) HPV coinfection, and PapilloCheck® microarray found 62.5% (50/80). Our Cohen's kappa results indicate that our in-house HPV genotyping testing (PCR-RFLP analysis) could be applied as a primary HPV test screening, especially in low income countries. If multiple HPV types are found in this primary test, a more descriptive test, such as PapilloCheck® microarray, could be performed.