Human papillomavirus DNA testing with the urine sample is not yet available: the accuracy of two distinct kits

SUMMARY OBJECTIVE: The aim of this study was to assess the results and efficiency of two real-time polymerase chain reaction procedures for detecting human papillomavirus utilizing urine samples. METHODS: This study comprised 151 patients who had previously tested positive for human papillomavirus in their cervical samples. Two different commercial real-time polymerase chain reaction techniques were used for identification and genotyping human papillomavirus in urine specimens. The urine samples of 151 patients were evaluated via the Roche Cobas test, and the urine samples of 91 patients were also evaluated via the Qiagen test. RESULTS: The overall consistency of urine and cervical swab specimens for the identification of human papillomavirus in Roche Cobas and Qiagen tests were 44.8 and 44%, respectively. The rates of positive human papillomavirus results from urine samples were 57 and 70.3%, respectively. The overall concordance among Roche Cobas and Qiagen tests utilizing urine samples for human papillomavirus type 16/18 was 84.3% with a kappa value of 0.675, and for other high-risk-human papillomavirus, it was 75.60% with a kappa value of 0.535. Roche Cobas showed high concordance with Qiagen test. CONCLUSION: human papillomavirus positivity was not detected in all urine samples. It is still inappropriate to recommend the use of urine liquid biopsy for the accurate and reliable detection of human papillomavirus. Due to the lack of a standardized tool, the utilization of urine samples as a screening human papillomavirus test remains a challenge.

Prevalence of high-risk human papillomavirus genotypes among apparently healthy women with normal and abnormal cervical cytology in Kaduna State, Nigeria

Background: About 99.7% of cervical dysplasia and cancer cases are caused by persistent genital high-risk human papillomavirus (hrHPV) infection. Most HPV infections are subclinical and self-limiting but may persists in about 5 to 10% of infected women, resulting in pre-cancerous lesions that can progress to invasive cancer years later. This study is aimed at detecting hrHPV among apparently healthy women of reproductive age in Kaduna State, thus providing more information for effective control of HPV and cervical cancer in Nigeria. Methodology: Cervical smears were taken from 515 randomly selected apparently healthy women across selected secondary and tertiary facilities from 3 Local Government Areas (LGAs) in each Senatorial Zone of Kaduna State, Nigeria. Liquid-based cytology (LBC) technique was used to collect cervical smears and prepare smears for cytology study, while the remaining samples were stored at -80oC for molecular studies. HPV DNA were extracted from the samples and amplified by convectional PCR using specific hrHPV (HPV 16,18,31 and 45) primer sets and a broad spectrum MY09/11 and GP5+/6+ primers for a wider range of HPV genotypes. Data were analysed using the Statistical Package for Social Sciences (SPSS) version 23.0 and relationship between prevalence of hrHPV and socio-demographic factors such as age and marital status were determined using Chisquare or Fisher Exact test with p<0.05 considered statistically significant. Results: The prevalence of total HPV and hrHPV infections in the study population was 11.8% (61/515) and 9.3% (48/515) respectively. A total of 100 HPV genotypes were detected by PCR in the 61 positive smears, with 66 hrHPV types from 48 women, and 34 other HPV types from 13 women. The frequency of hrHPV genotypes detected was HPV 31 (5.8%, n=30), HPV 45 (4.1%, n=21), HPV 16 (1.7%, n=9), and HPV 18 (1.2%, n=6), with other HPV genotypes (6.6%, n=34). The frequency of cervical dysplasia was 6.4% (33/515), which was significantly associated with all HPV genotypes except HPV 16. Single HPV infection was seen in 31 (51.8%) women while multiple infections were seen in 30 (49.2%), with double infection in 21 (34.4%) and triple infections in 9 (14.7%). Conclusion: The prevalence of hrHPV infection was high among women in Kaduna State, Nigeria. DNA-based screening for hrHPV genotypes and production of new vaccine that will protect against the predominant hrHPV genotypes are thus recommended for the prevention of cervical cancer in Nigeria, Africa and beyond.

Research progress on diabetes and human papilloma virus infection and vaccination / 公共卫生与预防医学

Diabetes is a common chronic non-infectious disease. Diabetic patients not only suffer from metabolic disorders, but are also prone to immune deficiencies and are at a higher risk of being infected with human papillomavirus (HPV). Many studies at home and abroad have shown that the HPV infection rate of patients with diabetes is higher than that of non-diabetic patients. Patients with diabetes can benefit from HPV vaccination, and the tolerance is good. HPV vaccination is recommended for diabetic patients. This article reviews the research on diabetes, HPV infection, and HPV vaccine, which will provide references for HPV vaccination in diabetic patients.

Genotipificación del virus del papiloma humano en mujeres embarazadas VPH positivas / Genotyping of human papillomavirus in HPV-positive pregnant women

Resumen Antecedentes: Las embarazadas infectadas por el virus del papiloma humano presentan condiciones médicas que influyen en el curso de la enfermedad y pueden potenciar la posibilidad de transmisión vertical. Objetivo: Identificar los genotipos del virus del papiloma humano más frecuentes en mujeres embarazadas. Método: Estudio retrospectivo, observacional y descriptivo. Se emplearon muestras de raspado cervical. La extracción de material genético se hizo por la técnica de fenol-cloroformo y se amplificó empleando iniciadores universales MY09/MY11. Las muestras positivas se genotipificaron con un kit que detecta 37 genotipos diferentes. Resultados: Se identificaron 341 genotipos. Los más frecuentes fueron 16 (10.3%), 52 (8.8%) y 59 (8.6%). En el 75.9% la detección fue con un genotipo y en el 42.7% se detectaron infecciones múltiples. Conclusiones: Es sabido que la infección por virus del papiloma humano en mujeres embarazadas raramente evolucionará a lesiones invasivas. Se deberán considerar tanto las posibles complicaciones obstétricas a corto y largo plazo, así como las posibles repercusiones en la salud del recién nacido. La detección elevada del genotipo 16 sugiere un seguimiento estrecho para considerar un abordaje óptimo posterior a la gestación.

Abstract Background: Pregnant women infected with human papillomavirus have medical conditions that influence the course of the disease and can increase the possibility of vertical transmission. Objective: To identify the most common human papillomavirus genotypes in pregnant women. Method: Retrospective, observational and descriptive study. Cervical scraping samples were used. The extraction of genetic material was done by the phenol-chloroform technique and was amplified using universal primers MY09/MY11. Positive samples were genotyped with a kit that detects 37 different genotypes. Results: Three hundred forty-one genotypes were identified. The most frequent were 16 (10.3%), 52 (8.8%), and 59 (8.6%). In 75.9% the detection was with one genotype and in 42.7% multiple infections were detected. Conclusions: It is known that human papillomavirus infection in pregnant women will rarely evolve to invasive lesions. Both possible short- and long-term obstetric complications, as well as possible repercussions on the health of the newborn, should be considered. The high detection of genotype 16 suggests close follow-up to consider an optimal post-pregnancy approach.

Using High-Resolution Anoscopy to Detect Anal Dysplasia Due to Papillomavirus in Patients with Inflammatory Bowel Disease

Introduction: Anal squamous cell carcinoma is rare, but its incidence and mortality have been increasing globally; 90% of cases are related to human papillomavirus (HPV) infection(1,2). Patients with inflammatory bowel disease (IBD) have a higher risk of infection with this virus; an incidence of 5.5 per 100,000 patients has been identified in the IBD group compared to 1.8 in the non-IBD group(3). Materials and methods: A descriptive case series study was conducted with 21 patients with IBD and no perianal symptoms between January and July 2022 at the Institute of Coloproctology in Medellín. They underwent anal cytology, HPV genotyping, and high-resolution anoscopy after explanation and acceptance of the procedure. If lesions were found, ablative treatment was performed. Results: 23% of this cohort had low-grade squamous lesions, while 14.2% had high-grade lesions with dysplasia changes during anoscopy. Besides, 90.4% had positive HPV genotyping, of which 76.1% were high-grade. Conclusions: Our study suggests that this series of patients with IBD behaves as a high-risk group for developing premalignant lesions in association with HPV. High-resolution anoscopy is a cost-effective, painless, and affordable method that, in expert hands, may impact the diagnosis and management of premalignant lesions and decrease the incidence of anal cancer in patients with IBD.

Introducción: El carcinoma anal de células escamosas es raro, pero su incidencia y mortalidad han ido en aumento globalmente. El 90% de los casos están relacionados con la infección por el virus del papiloma humano (VPH)1,2 y los pacientes con enfermedad inflamatoria intestinal (EII) tienen un mayor riesgo de infección por este virus; se ha identificado una incidencia de 5,5 por 100.000 pacientes en el grupo de EII frente a 1,8 en el grupo sin EII3. Metodología: Se realizó un estudio descriptivo de serie de casos en el que se incluyó a 21 pacientes con EII, sin síntomas perianales, entre enero y julio de 2022 en el Instituto de Coloproctología de Medellín, a quienes se les realizó citología anal, genotipificación del VPH y anoscopia de alta resolución, previa explicación y aceptación del procedimiento. Si se encontraban lesiones, se realizaba tratamiento ablativo. Resultados: El 23% de esta cohorte tenía lesiones escamosas de bajo grado, mientras que el 14,2% presentaba lesiones de alto grado con cambios de displasia al momento de la anoscopia. El 90,4% tenían genotipificación positiva para VPH, de los cuales el 76,1% eran de alto grado. Conclusiones: Nuestro estudio sugiere que esta serie de pacientes con EII se comporta como un grupo de alto riesgo para desarrollar lesiones premalignas en asociación con el VPH. La anoscopia de alta resolución es un método rentable, indoloro y asequible que, en manos expertas, puede impactar el diagnóstico y manejo de lesiones premalignas y disminuir la incidencia de cáncer anal en pacientes con EII.

Percepción de usuarios de Facebook sobre la vacuna contra el VPH en publicaciones del Ministerio de Salud de Perú a partir de procesamiento de lenguaje natural

El objetivo de este estudio fue describir las percepciones de los usuarios de Facebook que realizaron comentarios, en las publicaciones realizadas desde la cuenta oficial del Ministerio de Salud de Perú (MINSA), referentes a la campaña de vacunación contra el VPH. Se analizaron 2748 comentarios en Python con procesamiento de lenguaje natural. Con este proceso se obtuvieron palabras claves que luego fueron interpretadas de manera manual. Se encontraron mayoritariamente cuatro tipos de discursos dentro de ellos: a) apoyo a la publicación sobre la vacuna contra el VPH; b) rechazo a la vacuna contra el VPH; c) Vacuna contra el VPH en niños; d) Dudas sobre la vacuna contra el VPH. En su mayoría, los usuarios que expresaron una postura de rechazo de esta vacuna se respaldaban de links a noticias donde se presentaba un evento supuestamente atribuido a la vacunación o inmunización pero que carecía de una fuente de información confiable y/o verificable.

The objective of this study was to describe the perceptions of Facebook users who commented on posts made by the official account of the Ministry of Health of Peru (MINSA) regarding the HPV vaccination campaign. We analyzed 2748 comments in Python with natural language processing. With this process we obtained keywords that were then interpreted manually. We found mostly four types of discourse, within them: a) support for the publications of the HPV vaccine; b) refusal of the HPV vaccine; c) HPV vaccine in children; d) doubts about the HPV vaccine. For the most part, users who expressed a position against this vaccine relied on links to online news stories that presented an event supposedly attributed to vaccination or immunization but lacked a reliable and/or verifiable source of information.

Comparación de protocolos de vacunación contra el virus del papiloma humano en Ecuador y América Latina / Comparation of vaccination protocols against the human papillomavirus in Ecuador and Latin America

INTRODUCCIÓN: El virus del papiloma humano (VPH), con más de 100 tipos, es de transmisión sexual. Varios países de América Latina han introducido las vacunas contra el VPH. Aunque América Latina es la región que más rápido avanzó en la vacunación contra el VPH, sus sistemas de seguimiento y vigilancia son aún deficientes. OBJETIVO: Comparar las diferentes estrategias de vacunación contra el VPH en Ecuador y América Latina. MÉTODO: Revisión bibliográfica, en la que se obtuvo información de documentos gubernamentales y artículos indexados en los últimos 5 años sobre las estrategias de vacunación contra el VPH en Ecuador y América Latina. RESULTADOS: La mayoría de los países de América Latina han logrado introducir la vacuna contra el VPH, excepto Venezuela, Martinica, Haití, Nicaragua y Cuba. CONCLUSIONES: Los protocolos de vacunación de Ecuador y América Latina necesitan mejorar sus sistemas de seguimiento y aumentar la expansión de datos de cobertura disponibles de manera consistente. Actualmente siguen existiendo desafíos para introducir las vacunas, lograr una alta cobertura y fortalecer el seguimiento, la evaluación y la notificación.

INTRODUCTION: The human papilloma virus (HPV), with more than 100 types, is a sexual transmission infection. Many Latin American countries have introduced the vaccines against the HPV. Although Latin América is the region which advanced faster against the HPV, its surveillance and follow-up systems are yet deficient. OBJECTIVE: To compare the different strategies to assume the vaccination against the HPV in Ecuador and Latin America. METHOD: Bibliographic review, in which information was obtained from government documents and articles indexed in the last five years on vaccination strategies against HPV in Ecuador and Latin America. RESULTS: Most Latin American countries have managed to introduce the vaccine against the HPV, except Venezuela, Martinica, Haiti, Nicaragua and Cuba. CONCLUSIONS: The vaccination protocols of Ecuador and Latin América need to improve their systems of follow-up and monitoring, and increase the expansion of available data in a consistent manner. Now, there are still existing challenges to introduce the vaccines, manage a high reach and fortify the follow-up, the evaluation, and the notification.

¿Está la virtud en el punto medio? La incertidumbre del CIN2 y el papel del VPH / Is virtue at the midpoint? The uncertainty of CIN2 and the role of HPV

Objetivo: La biopsia guiada por colposcopia (BGC) marca el manejo de la neoplasia intraepitelial cervical. El objetivo de este estudio fue evaluar la concordancia de los resultados entre la BGC y la escisión amplia de la zona de transformación (LLETZ, large loop excision of the transformation zone), y la utilidad del genotipado del virus del papiloma humano (VPH) para seleccionar a las pacientes con riesgo de lesión intraepitelial escamosa de alto grado/neoplasia intraepitelial cervical 3 (HSIL/CIN3). Método: Se compararon los resultados de la BGC y de la LLETZ, siendo esta última el método de referencia. Se evaluó la relación del genotipo del VPH con el diagnóstico final de HSIL/CIN3. Resultados: La precisión de la biopsia comparada con LLETZ fue del 61,4%. La tasa de concordancia fue del 64,4% para CIN1, del 31,4% para CIN2 y del 77,4% para CIN3. La tasa global de sobrediagnóstico fue del 18,68% y la de subdiagnóstico del 19,89%. En mujeres menores de 30 años, la concordancia fue del 62,79% (CIN1 65%, CIN2 39,58% y CIN3 73,08%), la tasa de sobrediagnóstico del 22,67% y la tasa de subdiagnóstico del 15,11%. La infección por VPH16 tuvo una odds ratio de 3,86 para el diagnóstico final de HSIL/CIN3+. Conclusiones: El diagnóstico de CIN2 por BGC parece insuficiente para seleccionar a las pacientes para tratamiento escisional, principalmente en mujeres jóvenes. El hallazgo de VPH16 es un factor de riesgo de HSIL/CIN3+ independientemente del resultado de la biopsia.

Objective: Colposcopy-guided biopsy (CGB) is a basic tool for the management of cervical intraepithelial neoplasia. The aim of this study is to evaluate the concordance of results between CGB and large loop excision of the transformation zone (LLETZ), and the usefulness of human papillomavirus (HPV) genotyping to select patients at risk of H-SIL/CIN3. Method: The results of colposcopy-guided biopsy and LLETZ were compared, with LLETZ being the gold standard. The relationship of HPV genotype to the final diagnosis of CIN3 was assessed. Results: The accuracy of CGB compared to LLETZ was 61.4%. The concordance rate was 64.4% for CIN1, 31.4% for CIN2 and 77.4% for CIN3. The overall overdiagnosis rate was 18.68% and underdiagnosis rate was 19.89%. In women under 30 years of age the concordance rate was 62.79% (CIN1 65%, CIN2 39.58% and CIN3 73.08%), and the rate of overdiagnosis and underdiagnosis was 22.67% and 15.11%, respectively. HPV16 infection had an odds ratio of 3.86 for the final diagnosis of CIN3+ and the result was significant regardless of the biopsy result. Conclusions: The CGB result as CIN2 is inaccurate and seems insufficient to select patients for excisional treatment, mainly in young women. HPV16 infection is a risk factor for CIN3+ regardless of the colposcopy-guided biopsy result.

Neoplasia cervical e infección por virus del papiloma humano como factores de riesgo para desarrollo de cáncer anal y lesiones precursoras / Cervical neoplasia and human papilloma virus infection as risk factors for the development of anal cancer and precursor lesions

RESUMEN La incidencia del cáncer anal ha presentado un incremento en los últimos 10 años, sobre todo en población considerada vulnerable. Las mujeres con antecedentes de infección por Virus del Papiloma Humano (VPH) en el tracto genital, tienen mayor riesgo de este tipo de cáncer. Se ha demostrado que, la infección con genotipos de VPH de alto riesgo (AR), en la región anogenital, desempeña un papel en la etiopatogenia de dicho cáncer. Se desconocen muchos aspectos de la historia natural de las lesiones anales, pero se considera que la zona de transición anal presenta un alto recambio celular, por lo que se ha planteado un mecanismo fisiopatológico de infección por VPH-AR y desarrollo de lesiones invasoras, similar al del cáncer cervical. El objetivo de este trabajo fue mostrar el estado actual sobre la información epidemiológica que vincula el riesgo de desarrollar cáncer anal en mujeres con lesiones precursoras de cáncer cervical asociadas a la infección por VPH. La relevancia de dicha información es proporcionar una base de recomendaciones para la detección oportuna de cáncer anal en mujeres consideradas de AR de padecerlo y, favorecer la realización de estudios prospectivos en la población.

ABSTRACT The incidence of anal cancer has increased in the last 10 years, especially in the population considered to be at risk. Women with a history of infection in the genital tract by Human Papillomavirus (HPV) have higher risk of developing this type of cancer. The presence of high-risk (HR) HPV genotypes in the anogenital region has been shown to play a role in the etiopathogenesis of anal cancer. Many aspects of the natural history of anal lesions are unknown, but the anal transition zone is considered to have a high cell replacement. This is why a pathophysiological mechanism of HR-HPV infection and development of invasive lesions similar to those of cervical cancer has been suggested. The aim of this work was to show the current status of the epidemiological information that links the risk of developing anal cancer in women with cervical cancer precursor lesions associated with HPV infection. The relevance of this information is to provide a basis of recommendations for the timely detection of anal cancer in women considered to be at HR of suffering it, and to encourage more prospective studies in this population.

A New Brazilian Device for Cervical Cancer Screening: Acceptability and Accuracy of Self-sampling / Um Novo Dispositivo Brasileiro para Diagnóstico de Câncer Cervical: Aceitabilidade e Precisão da Autoamostragem

Abstract Objective To evaluate the accuracy and patient acceptability toward self-sampling using a new device - SelfCervix® - for detecting HPV-DNA. Methods A total of 73 women aged 25-65 who underwent regular cervical cancer screening from March to October 2016 were included. Women performed self-sampling followed by a physician-sampling, and the samples were analyzed for HPV-DNA. After that, patients were surveyed about their acceptability of self-sampling. Results HPV-DNA detection rate of self-sampling presented high accuracy and was similar to physician-collection. Sixty-four (87.7%) patients answered the acceptability survey. Most patients (89%) considered the self-sampling comfortable, and 82.5% preferred self-sampling to physician-sampling. The reasons cited were time-saving and convenience. Fifty-one (79.7%) reported that they would recommend self-sampling. Conclusion Self-sampling using the new Brazilian device SelfCervix® is not inferior in HPV-DNA detection rate compared with physician-collection, and patients are supportive of the method. Therefore, it might be an option to reach under-screened populations in Brazil.

Resumo Objetivo Avaliar a acurácia e aceitabilidade da auto-coleta utilizando um novo coletor - SelfCervix® - para a detecção de DNA de HPV. Métodos Foram incluídas no estudo 73 mulheres com idade entre 25-65 anos que realizaram seu rastreamento regular do câncer de colo do útero entre Março e Outubro de 2016. Estas mulheres realizaram a auto-coleta, seguida de coleta profissional e as amostras foram analisadas paraa presença de DNA de HPV. Após, elas responderam um questionário sobre a experiência da auto-coleta. Resultados As taxas de detecção de DNA de HPV por auto-coleta foram altas e similares as da coleta profissional. Sessenta e quatro (87,7%) pacientes responderam o questionário de experiência. A maioria (89%) considerou a auto-coleta confortável, e 82,5% preferiram o método comparado a coleta profissional. As razões citadas foram economia de tempo e conveniência. Cinquenta e uma (79,7%) mulheres confirmaram que recomendariam a auto-coleta. Conclusão Auto-coleta utilizando o novo coletor desenvolvido no Brasil não é inferior na detecção de DNA de HPV quando comparada a coleta profissional, e apresenta uma boa aceitabilidade pelas mulheres. Desta maneira, pode ser uma opção para alcançar populações que não realizam o rastreamento padrão.

Efficacy of Different Pharmacological Interventions for Cervical High-risk HPV Infection: Bayesian Network Meta-analysis / 肿瘤防治研究

Objective To compare the efficacy of common clinical interventions in the treatment of cervical high-risk (HR) HPV infection based on Bayesian network meta-analysis. Methods Randomized controlled trials (RCTs) about common clinical interventions for cervical HR-HPV infection were searched in PubMed, Web of Science, Embase, The Cochrane Library, CBM, CNKI, Wanfang Data, and VIP databases from inception to July 31, 2021 using specific inclusion and exclusion criteria. The quality of the included studies was evaluated in accordance with the Cochrane systematic review manual. Meta-analysis was performed with Stata16 and RevMan5.3 software. Results Seventy-three RCTs were included, involving 3642 patients and eight treatment methods. Network meta-analysis showed that in the three months after treatment, the negative conversion rate was in the order: PTL > anti-HPV BPD > ALA-PDT > Nr-CWS > BFKS > CSJZS > rhIFNα-2b > FUO. In the six months after treatment, the negative conversion rate was in the order: Nr-CWS > ALA-PDT > PTL > anti-HPV BPD > BFKS > rhIFNα-2b > FUO > CSJZS. In the nine months after treatment, the negative conversion rate was in the order: PTL > ALA-PDT > BFKS > anti-HPV BPD > rhIFNα-2b > FUO. IN the 12 months after treatment, the negative conversion rate was in the order: Nr-CWS > ALA-PDT > anti-HPV BPD > PTL > BFKS > rhIFNα-2b > FUO > CSJZS. Conclusion In terms of HPV negative conversion rate, Nr-CWS and PTL are more effective and currently ideal compared with the other treatments. Owing to the quality of the evidence, the above conclusions must be confirmed by future high-quality studies.

Infection of human papillomavirus and head and neck cancer / 中华肿瘤杂志

High-risk human papillomavirus (HPV)-related cancers consist of cervical cancer, anal cancer, penile cancer, vulvar cancer, vaginal cancer, and head and neck cancer (HNC). Of these, the disease burden of HNC is second only to cervical cancer. HNC mostly originates from malignant lesions of squamous epithelial cells and mainly includes oral cavity cancer, pharyngeal cancer (including nasopharyngeal cancer, oropharyngeal cancer, and hypopharyngeal cancer), and laryngeal cancer. Tobacco use, alcohol abuse, and HPV infection are three primary risk factors. Recently, there is an upward trend of HNC incidence globally, especially in high-income countries. In China, the disease burden and trends of HPV-related HNC are still not clear. A few small sample size and single-center studies suggest a high HPV prevalence and increasing trend in HNC. Methodological differences in HPV testing and regional variabilities still exist among these studies. Among the anatomic sites, oropharyngeal cancer has been shown to be caused by HPV infection, but the association of HPV with other sites is still under debate. In addition, there is a paucity of relevant studies. Here, this review narrates the association between HPV infection and HNC, compares the differences between global and Chinese studies, and then explores the importance of HPV infection in various anatomical sites. The main objective is to highlight the research on HPV-related HNC and promote relevant prevention and treatment programs.

Assessment of the diagnostic value and prognosis of different detection markers in endocervical adenocarcinoma / 中华肿瘤杂志

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.

Impacto da imunização contra o papilomavírus humano na prevenção do câncer do colo do útero: uma revisão integrativa / Impact of immunization against human papillomavirus in the prevention of cervical cancer: an integrative review / Impacto de la inmunización contra el virus del papiloma humano en la prevención del cáncer de cuello uterino: una revisión integradora

Esta revisão integrativa teve como objetivo identificar na literatura a produção científica que estabeleça uma relação entre a vacinação contra o HPV e a prevenção do câncer do colo uterino. No período entre 24 de março e 28 de abril de 2023, foi realizada a busca bibliográfica seguindo os critérios de inclusão: artigos publicados nos últimos cinco anos, em português, inglês ou espanhol e Qualis CAPES mínimo B2. Para alcançar os objetivos dessa revisão, foram selecionados artigos a partir da análise dos títulos, dos resumos e da leitura integral, excluindo em cada etapa os que não se enquadravam nos critérios pré-estabelecidos. Após busca na base de dados, foram localizados um total de 973 artigos, 58 na PubMed e 915 na Biblioteca Virtual em Saúde. Destes, apenas oito artigos atenderam a todos os critérios e foram incluídos na presente revisão. Os trabalhos incluídos foram publicados, entre os anos de 2018 e 2022, em periódicos internacionais. Existem diversas evidências da relação entre a vacinação contra o HPV e a prevenção do câncer de colo uterino. Porém, a taxa de adesão à vacina ainda é muito baixa, por mais que esta tenha um papel fundamental na prevenção do câncer cervical, bem como na prevenção do câncer de pênis, anal e orofaríngeo e outras infecções pelo HPV.

This integrative review aimed to identify in the literature the scientific production that establishes a relationship between the immunization against HPV and the prevention of cervical cancer. In the period between 24 March and 28 April 2023 it was made a bibliography research following the inclusion criteria: articles published in the last five years, in Portuguese, English or Spanish, and Qualis CAPES minimum as B2. To reach this review goals, there were selected articles based on title analysis, summary and unabridged reading, excluding, in every stage, those that did not enter the preestablished criteria. After the research in the data base, there was found the total of 973 articles, 58 in PubMed and 915 in Virtual Health Library. Only eight articles met all criteria and were included in this review. All the articles included were published, between 2018 and 2022, in international periodicals. There is evidence of a link between HPV vaccination and the prevention to cervical cancer. However, the adhesion to the vaccine is still very low, even if it has a fundamental role in the prevention to cervical, penile, anal and oropharyngeal cancer, as well as in the prevention of other HPV infections.

Esta revisión integradora tuvo como objetivo identificar en la literatura la producción científica que establece una relación entre la inmunización contra el VPH y la prevención del cáncer de cuello uterino. En el período comprendido entre el 24 de marzo y el 28 de abril de 2023 se realizó una investigación bibliográfica siguiendo los criterios de inclusión: artículos publicados en los últimos cinco años, en portugués, inglés o español, y Qualis CAPES mínimo como B2. Para alcanzar los objetivos de esta revisión, se seleccionaron los artículos a partir del análisis del título, resumen y lectura íntegra, excluyendo, en cada etapa, aquellos que no entraban en los criterios preestablecidos. Después de la pesquisa en la base de datos, se encontró el total de 973 artículos, 58 en PubMed y 915 en la Biblioteca Virtual de Salud. Sólo ocho artículos cumplieron todos los criterios y fueron incluidos en esta revisión. Todos los artículos incluidos fueron publicados, entre 2018 y 2022, en publicaciones periódicas internacionales. Existen evidencias de la relación entre la vacunación frente al VPH y la prevención del cáncer de cuello de útero. Sin embargo, la adhesión a la vacuna es todavía muy baja, aunque tenga un papel fundamental en la prevención al cáncer de cuello uterino, pene, ano y orofaringe, así como en la prevención de otras infecciones por VPH.

High prevalence of HPV 18 and multiple infections with oncogenic HPV genotypes in women at risk of cervical cancer examined in Manaus, Brazil

Cervical cancer is a serious public health problem in Brazil, especially in Manaus (Amazonas), the city with the highest incidence rate of cervical cancer in the country. Persistent infection with oncogenic human papillomavirus (HPV) genotypes is the cause of disease development. The aim of this study was to investigate the prevalence of oncogenic genotypes in women at high risk for cervical precancer examined in two policlinics in Manaus. One hundred and two patients who underwent colposcopy took part in the research. The DNA samples obtained from the cervical epithelium were analyzed by PCR with type-specific primers for the detection of eight oncogenic genotypes, which were chosen based on previous studies. The presence of HPV virus was detected in all samples. The most prevalent oncogenic genotypes were 18 (47.1%) and 16 (45.1%). Interestingly, HPV 18 was considered uncommon in this region. In addition to these, genotypes 31 (19.6%), 58 (19.6%), 33 (18.6%), and 45 (15.7%) also had a relatively high frequency in this population. Fifty-six women (54.9%) had multiple infections with up to five oncogenic types. Also, the presence of genotypes other than 16 and 18 was observed in most samples (57.8%), which also deserves attention since they are not covered by currently available vaccines against HPV in Brazil. The high prevalence and multiple infections with several oncogenic HPV genotypes in association with precursor lesions for cervical cancer highlighted the need to improve strategies to prevent this disease in Amazonas.

Association of human papillomavirus (HPV), p16, p53 and p63 expression with non-bilharzia-associated squamous cell carcinoma of the bladder and algorithm construction for histopathological grading prediction

ABSTRACT Objective To investigate the expression of human papillomavirus (HPV), p16, p53, and p63 in non-schistosomiasis-related squamous cell carcinoma of the bladder and to develop an accurate and automated tool to predict histological classification based on clinicopathological features. Methods Twenty-eight patients with primary bladder pure squamous cell carcinoma who underwent cystectomy or transurethral resection of bladder tumor (TURBT) for bladder cancer between January 2011 and July 2017 were evaluated. Clinical data and follow-up information were obtained from medical records. Formalin-fixed, paraffin-embedded surgical specimens were used for immunohistochemical staining for p16, p53, and p63. Human papillomavirus detection was evaluated by PCR. Statistical analysis was performed, and statistical significance was set at p<0.05. Finally, decision trees were built to classify patients' prognostic features. Leave-one-out cross-validation was used to test the generalizability of the model. Results Neither direct HPV detection nor its indirect marker (p16 protein) was identified in most cases. The absence of p16 was correlated with less aggressive histological grading (p=0.040). The positive p16 staining detection found only in pT1 and pT2 cases in our sample suggests a possible role for this tumor suppressor protein in the initial stages of bladder squamous cell carcinoma. The decision trees constructed described the relationship between clinical features, such as hematuria/dysuria, the level of tumor invasion, HPV status, lymphovascular invasion, gender, age, compromised lymph nodes, and tumor degree differentiation, with high classification accuracy. Conclusion The algorithm classifier approach established decision pathways for semi-automatic tumor histological classification, laying the foundation for tailored semi-automated decision support systems for pathologists.

Anal cancer in systemic lupus erythematosus patients is a neglected condition / Câncer anal em pacientes com lúpus eritematoso sistêmico é uma condição negligenciada

Patients with systemic lupus erythematosus have a higher incidence of neoplasms associated with human papillomavirus infections, such as those that affect the vulva, the vagina, and the cervix; however, little is known about the frequency of anal cancer among these patients. Although there are recommendations for screening for this cancer in immunosuppressed individuals, it is possible that this procedure is not strictly followed. We describe the case of a 47-year-old woman with systemic lupus erythematosus who was treated with immunosuppressants and developed advanced anal squamous cell carcinoma after adequate treatment and healing of a high-grade cervical squamous intraepithelial lesion. Five years after the completion of the anal cancer treatment, the patient presented with cystic hepatic lesions that were histopathologically confirmed to be metastatic squamous cell carcinoma. This report aimed to highlight the need for anal cancer screening in patients with lupus, particularly if there was a history of cervical cytopathological alterations. (AU)

Resumo Pacientes com lúpus eritematoso sistêmico apresentam maior incidência de neoplasias associadas a infecções por HPV, como aquelas que acometem a vulva, a vagina e o colo do útero, mas pouco se sabe sobre a frequência de câncer anal entre essas pacientes. Embora existam recomendações para o rastreamento desse câncer em indivíduos imunossuprimidos, é possível que esse procedimento não esteja sendo rigorosamente seguido. Descrevemos uma mulher de 47 anos com lúpus eritematoso sistêmico, tratada com imunossupressores, que desenvolveu um carcinoma escamocelular anal avançado após tratamento adequado e cicatrização de lesão intraepitelial escamosa cervical de alto grau. Cinco anos após o término do tratamento do câncer anal, a paciente apresentou lesões císticas hepáticas cujo resultado citopatológico confirmou ser carcinoma escamocelular metastático. O presente relato teve como objetivo chamar atenção para a necessidade do rastreamento do câncer anal em pacientes com lúpus, principalmente se houver história prévia de alterações citopatológicas cervicais. (AU)

Small cell neuroendocrine carcinoma with adenocarcinoma and high grade squamous intraepithelial neoplasia of the cervix

ABSTRACT Neuroendocrine neoplasm (NEN) of the cervix is a malignant tumor and is classified into low and intermediate-grade neuroendocrine tumor (NET), and high-grade small cell neuroendocrine carcinoma (SCNEC), and large cells neuroendocrine carcinoma (LCNEC). SCNEC of the cervix is an Infrequent tumor with an incidence of less than 1% of all gynecological malignancies. It is characterized by small to medium-sized tumor cells with scant cytoplasm and neuroendocrine differentiation. Most cases of SCNEC of the cervix manifest in pure forms, and only cases show coexisting, non-neuroendocrine component of HPV-associated adenocarcinoma or squamous cell carcinoma. In this report, reviewing the literature, we present one such unique case of SCNEC of the cervix with adenocarcinoma and high-grade squamous intraepithelial neoplasia.

Clarity of publications on HPV in Instagram profiles of official health agencies in Brazil

Abstract The study analyzed the clarity of publications on human papillomavirus (HPV) in the Instagram profiles of official Brazilian health agencies. An infodemiological study analyzed publications on HPV in the 81 Instagram profiles selected from the Health Ministry, States' Health Departments, and dental councils and associations. The following data were collected: classification of content, type of profiles, type of media, how the content was addressed, number of posts, frequency, likes, comments, viewings, and hashtags, and how the HPV vaccine was addressed. The clarity of the educational publications was assessed using the Brazilian version of the Clear Communication Index (BR-CDC-CCI). Data analysis was performed with Spearman's correlation and the Mann-Whitney test (p < 0.05). A total of 504 publications on HPV were found. The average number of likes was 528.3 (SD = 2388.2) and the average BR-CDC-CCI score was 67.1 (SD = 14.1). The quality and clarity of the information was considered adequate (BR-CDC-CCI score ≥ 90) in 6.9% of the publications. A weak positive correlation was found between the number of likes and both the BR-CDC-CCI score (r = 0.195) and number of posts (r = 0.124). Publications from the Health Ministry had a significantly higher BR-CDC-CCI score (72.9) compared to the other profiles analyzed (p = 0.01). Most publications concerned government actions, had low engagement, and written educational information was of low clarity and quality. However, the effort to reach the population was evident, with an increase in publications over the years.

Diga sim à vacina contra o papilomavírus humano: produção e validação de um guia ilustrado / Diga sí a la vacuna contra el papilomavirus humano: producción y validación de una guía ilustrada / Say yes to the human papillomavirus vaccine: production and validation of an illustrated guide

Objetivos: produzir e validar um guia ilustrado como recurso tecnológico de informação para meninos e meninas sobre a vacina contra o Papilomavírus Humano. Método: estudo metodológico, conduzido em ambiente virtual guiado pelo modelo ADDIE (Analysis, Design, Development, Implementation e Evaluation) e pelo Design Instrucional Contextualizado. Participaram da validação de conteúdo e aparência 35 experts da área da saúde e 35 de outras áreas. Na avaliação semântica, participaram 20 meninos e 22 meninas. Resultados: a tecnologia educacional desenvolvida foi um guia ilustrado, constituído de 13 tópicos. A validação de conteúdo global foi 0,91; a validação de aparência, 0,95. Na avaliação, os textos tiveram 94,8% e as ilustrações, 88,8% de acordo total. A versão final constituiu-se de 18 páginas nas versões impressa e digital. Considerações finais: o guia mostrou-se válido e adequado para veicular informações com potencial enquanto recurso didático, para mediar práticas educativas com meninos e meninas sobre a vacina contra o Papilomavírus Humano.

Objetivos: producir y validar una guía ilustrada como recurso tecnológico de información para niños y niñas sobre la vacuna contra el Virus del Papiloma Humano. Método: estudio metodológico, conducido en ambiente virtual guiado por el modelo ADDIE (Analysis, Design, Development, Implementation y Evaluation) y por el Design Instrucional Contextualizado. Participaron en la validación de contenido y apariencia 35 experts en salud y 35 de otras áreas. En la evaluación semántica, participaron 20 niños y 22 niñas. Resultados: la tecnología educativa desarrollada fue una guía ilustrada, constituida por 13 tópicos. La validación de contenido global fue 0,91; la validación de apariencia, 0,95. En la evaluación, los textos tuvieron 94,8% y las ilustraciones, 88,8% de acuerdo total. La versión final constaba de 18 páginas en las versiones impresa y digital. Consideraciones finales: la guía se mostró válida y adecuada para transmitir información con potencial como recurso didáctico, para mediar prácticas educativas con niños y niñas sobre la vacuna contra el Virus del Papiloma Humano.

Objective: to produce and validate an illustrated guide as a technological resource of information for boys and girls about the vaccine against the Human Papillomavirus. Method: methodological study, conducted in a virtual environment guided by the ADDIE (Analysis, Design, Development, Implementation and Evaluation) model and by the Contextualized Instructional Design. The participants in the validation of content and appearance were 35 experts in the health area and 35 from other areas. In the semantic evaluation, 20 boys and 22 girls participated. Results: the developed educational technology was an illustrated guide, consisting of 13 topics. Overall content validation was 0.91; appearance validation was 0.95. In the evaluation, the texts had 94.8% and the illustrations, 88.8% of total agreement. The final version consisted of 18 pages in print and digital versions. Final considerations: the guide proved to be valid and adequate to convey information with potential as a didactic resource to mediate educational practices with boys and girls about the vaccine against the Human Papillomavirus.