Research progress on the treatment improvement of HPV-associated oropharyngeal cancer / 临床耳鼻咽喉头颈外科杂志

The number of new cases of oropharyngeal cancer is increasing year by year among the world, and HPV infection is one of the risk factors for this malignant tumor. Compared with HPV-negative oropharyngeal cancer, HPV-positive patients are more sensitive to radiotherapy and have a better prognosis, but there is no accepted treatment for HPV-positive patients. Reducing treatment intensity moderately and exploring the best option to minimize side effects of treatment are urgent issues to be addressed. This article reviews the research progress on the treatment improvement of HPV-associated oropharyngeal cancer in recent years.

Factors Associated with Presence of Human Papillomavirus Infection among Women: Findings from New Cervical Cancer Screening in Kelantan, Malaysia

@#Introduction: Human papillomavirus (HPV) infection is known to cause cervical cancer worldwide. Recently, Malaysia introduced HPV DNA detection testing for cervical cancer screening program. However, knowledge regarding factors for HPV infection among women still limited. Thus, this study aimed to determine the prevalence and factors associated with HPV infection among women in Kelantan, a north-eastern state of Malaysia. Methods: This study used secondary data extracted from HPV DNA test registry book and HPV DNA laboratory request forms. Data on all Malaysian women aged 30 to 49 years old in 2019 reported in registry book were included. Simple random sampling was applied. All information from book and forms were collected using proforma and analysed using SPSS. The outcomes were categorised into HPV infection and non-HPV infection. The parameters related to factors associated with HPV infection were determined using multivariable logistic analysis. Results: The prevalence of HPV infection among women attending the new cervical screening was 8.4% (95% CI 6.4%, 10.3%). Those aged between 30 and 39 years old (AdjOR 2.09; 95% CI 1.16, 3.78, p=0.014), had 5 or more parities (AdjOR 2.82; 95% CI 1.58, 5.06, p<0.001) and hormonal contraception users (AdjOR 7.48; 95% CI 4.07, 13.76, p<0.001) were significantly associated with HPV infection. Conclusion: Overall, the prevalence of HPV infection from this study is comparable to the local and international studies. Age, number of parities and hormonal contraception users influence the HPV infection. This finding could help in designing more targeted screening for cervical cancer.

Safety of human papilloma virus vaccine based on Vaccine Adverse Event Reporting System from 2006 to 2021 / 中国生物制品学杂志

@#Objective To investigate the characteristics of distribution of adverse event(AE)associated with human papillomavirus(HPV)vaccine by analysis of data on AE collected from the Vaccine Adverse Event Reporting System(VAERS).Methods The data on AE reported in VAERS from January 1st,2006 to December 31st,2021 were analyzed and compared by using Pearson Chi-square test and Mann-Whitney U test.Results A total of 53 571 cases of AE were included in the study,in which the ratio of male to female was 0. 25∶1,and the median age of vaccinees was 15 years. A portion of 36. 1%of AE occurred after the first dose,while 90. 7% occurred within 3 d after vaccination. Both the gender ratios(χ~2=72. 570,P < 0. 001) and the median ages(Z = 4. 255,P < 0. 001)of vaccinees in non-serious and serious adverse event(SAE)showed significant difference. In terms of classification of SAE,hospitalization,prolonged hospitalization and disability were more common in females than in males,of which the percentages decreased with the increasing age. Among the AE,syncope was the most common clinical symptom. In the SAE,the highest proportion of deaths was caused by HPV2 vaccine,which was 19. 0%. The proportion of prolonged hospitalization caused by HPV4 vaccine was higher than that by HPV9vaccine. In general,HPV4 vaccine was more prone to cause SAE than HPV9 vaccine(χ~2=183. 267,P < 0. 001).Conclusion In all the AE,the largest proportion occurred in the age group of 9 ～ 17 years,followed by those in the groups of 18 ～ 26 and 27 ～ 45 years. Most of the AE occurred after the first dose. The clinical symptoms of AE caused by three vaccines were different. The analysis of distribution characteristics of AE may provide a reference for the study on clinical safety of HPV vaccine and optimization of vaccination.

Effects of recombinant human interferon α2a suppository on levels of inflammatory factors in cervical mucus of HPV-infected patients / 中国生物制品学杂志

@#Objective To investigate the effects of recombinant human interferon α2a(rhIFNα2a) suppository on the levels of inflammatory factors in the cervical mucus of patients infected with human papillomavirus(HPV).Methods A total of60 HPV-positive patients admitted to the Second Affiliated Hospital of Xi'an Jiaotong University from March to August in 2022 were selected as study objects,and then divided into observation and control groups,30 cases for each group,according to the random number table method.The observation group was given rhIFNα2a suppository therapy by vaginal medication,once every other day,continuous 10 times a month as a course of treatment,and 3 consecutive courses of treatment.The control group did not use drugs.The cervical secretions were collected and the levels of IL-1β,IL-2R,IL-6,IL-8,IL-10 and tumor necrosis factor-α(TNF-α) were measured by chemiluminescence assay.Results After 3 months of treatment,the levels inflammatory factors IL-1β,IL-6,IL-8 and TNF-α in cervical mucus of patients in the observation group were significantly lower than those in the control group(t=-2.717,-2.686,-3.178 and-3.25,respectively,each P <0.05).Compared with before treatment,the levels of IL-1β,IL-6,IL-8 and TNF-α in cervical mucus of patients in the observation group also decreased significantly(t=5.934,4.092,6.495 and 3.287,respectively,each P <0.01),while in the control group,only the level of IL-8 in cervical mucus was significantly different(t=2.345,P=0.024).Conclusion rhIFNα2a suppository can reduce the level of inflammatory factors in cervical mucus,attenuate the inflammatory response and accelerate the clearance of HPV.

Distribución de virus de papiloma humano de alto riesgo oncogénico y otras infecciones de transmisión sexual en mujeres paraguayas con y sin virus de la inmunodeficiencia humana

El virus de papiloma humano de alto riesgo oncogénico (VPH-AR) es causa necesaria pero no suficiente para la ocurrencia de cáncer de cuello uterino (CCU). Mujeres portadoras del virus de inmunodeficiencia humana (VIH) presentan mayor riesgo de desarrollar lesiones precursoras del cáncer de cuello de útero, por ello, el objetivo del presente trabajo prospectivo de corte transversal fue determinar la frecuencia de VPH-AR y otras infecciones de transmisión sexual-ITS (condilomas, sífilis, virus del herpes simple, gonorrea, citomegalovirus, hepatitis B) en 218 mujeres con y sin VIH que acudieron al Programa Nacional de Lucha contra el SIDA (PRONASIDA) desde julio 2017 hasta marzo 2021. Se encontró que 16/54 (29,6%) mujeres VIH-positivas presentaron infección por VPH-AR en comparación a 41/164 (25%) mujeres VIH-negativas (p>0,05). En relación a la edad, mujeres VIH positivas presentaron una frecuencia comparable de infección por VPH-AR (30 años 30,2%), a diferencia de mujeres VIH negativas donde hubo una disminución significativa de la infección por VPH-AR luego de los 30 años (30 años 18,8%, p= 0,028). Esto podría explicarse por la inmunosupresión observada en mujeres VIH positivas que podría favorecer infecciones persistentes, sugiriendo que deben ser controladas más cercanamente. Además, se observó mayor frecuencia de otras ITS en mujeres VIH positivas (29,6% vs 15,8%, p=0,026), lo cual sugiere que aparte del monitoreo más cercano, es fundamental fortalecer la educación sobre factores de riesgo para la ITS sobre todo VPH y VIH, así como la realización de prevención primaria por vacunación contra el VPH.

High-risk human papillomavirus (HPV-HR) is a necessary but not sufficient cause for cervical cancer (CC). Women carriers of human immunodeficiency virus (HIV) present an increased risk for the development of cervical cancer precursor lesions, therefore, the objective of the present prospective cross-sectional study was to determine the frequency of HPV-HR and other sexually transmitted infections-STIs (condylomas, syphilis, herpes simplex virus, gonorrhoea, cytomegalovirus, hepatitis B) in 218 women with and without HIV who attended the Ministry of Health from July 2017 to March 2021. It was found that 16/54 (29.6%) HIV-positive women had HPV infection compared to 41/164 (25%) HIV-negative women (p>0.05). In relation to age, HIV-positive women had a comparable frequency of HPV infection (30 years 30.2%), unlike HIV-negative women whom above 30 years of age presented a significant decrease in HPV-AR infection (30 years 18.8%, p:0.028). This could be explained by the immunosuppression observed in HIV-positive women which could favour persistent infections, suggesting that they should be controlled more closely. In addition, other STIs were observed to be more frequent in HIV-positive women (29.6% vs 15.8%, p:0.026), which suggests that apart from closer monitoring, it is essential to strengthen education on risk factors for STIs, especially HPV and HIV, as well as the implementation of primary prevention by vaccination against HPV.

Cáncer de cérvix: una mirada práctica / Cervical cancer, a practical view

Resumen Introducción: El cáncer de cérvix (CC) es un problema de salud pública en países desarrollados y no desarrollados; esta patología tiene repercusiones socioeconómicas en mujeres en edad reproductiva. Objetivo: Describir las características sobre métodos de prevención, tamizaje, diagnóstico y tratamiento del cáncer de cérvix. Método: Se realizó una búsqueda bibliográfica exhaustiva en un período de seis años (2016-2021) en la base de datos de la Fundación Universitaria del Área Andina, utilizando motores de búsqueda como Dialnet, Science Direct, Medline, LIlacs, Scopus para revisar los conceptos generales sobre cáncer de cérvix. Resultados: El CC es el segundo cáncer más frecuente en Colombia, la principal etiología del cáncer de cérvix es el virus del papiloma humano (VPH), el cual es un virus prevenible mediante la adecuada educación e información y seguimiento a sus lesiones precancerosas. Conclusión: El CC es una patología con altas tasas de mortalidad, especialmente en países en vía de desarrollo y en las infecciones asociadas a VPH de alto riesgo, afectando principalmente a mujeres en edad reproductiva y estratos socioeconómicos bajos. Los principales pilares para el manejo de esta patología siguen siendo las estrategias de salud pública, como la vacunación y realización de las pruebas de tamizaje.

Abstract Introduction: Cervical cancer (CC) is a public health problem in both developed and undeveloped countries; besides it has socio-economic repercussions in women of reproductive age. Objective: To describe the characteristics of cervical cancer prevention, screening, diagnosis, and treatment methods. Method: An exhaustive bibliographic search was carried out within a period of 6 years (2016-2021) in the database of the Fundación Universitaria del Área Andina, using search engines such as Dialnet, Science Direct, Medline, Lilacs, and Scopus to review the concepts general information about cervical cancer. Results: The main etiology of cervical cancer is the human papillomavirus (HPV) which is a preventable virus through adequate education and information and follow-up of its precancerous lesions. It is the second most frequent cancer in Colombia. Conclusion: CC is a pathology that mainly affects women of reproductive age belonging to low socioeconomic strata. This type of cancer has high mortality rates, especially in developing countries and in high-risk HPV infections. Regarding the management of this pathology, public health strategies, such as vaccination and conducting screening tests continue being the fundamental pillars.

Factors influencing women to participate in cervical cancer screening by providing menstrual pads: A population?based study from rural areas of Maharashtra State, India

Background: India accounts for a quarter of the world cervical cancer burden. Cervical cancer is highly preventable. However, low level of participating women in screening is one of the major issues. The aim of this work was to study the factors that influence women to participate in cervical cancer screening by providing menstrual pads for human papillomavirus (HPV) testing. Methods: Menstrual clothes were collected from two different populations from the rural areas of Maharashtra state for HPV testing to screen for cervical cancer. For this study, out of 945 participated women, 557 (58.9%) provided their menstrual pads. Multivariate logistic regression was applied to calculate the odds ratio (OR) and 95% confidence interval (95% CI). Results: The probability of providing the menstrual pads was high among the women who were highly educated compared to those with less education (OR: 1.4; 95% CI: 1.0–1.9), having mobile phone facilities as compared to those with no mobile phones (OR: 1.4; 95% CI: 1.0–2.0), who were using new cloths as menstrual pads compared to those who did not use the same (OR: 8.5; 95% CI: 5.0–14.3), who did not have tobacco habit as compared to those who had tobacco habit (OR: 1.4; 95% CI: 1.1–1.9) and in the village where health worker was stationed as compared to the village where health worker was not stationed (OR: 1.8; 95% CI: 1.4–2.5). Conclusion: Factors including health worker availability, using mobile phones for communication and high education level facilitate women’s participation. To improve the participation, there is need to apply special strategies for older age group, less educated women and women having tobacco habit.

Usos conceptuales del género y la vulnerabilidad en políticas públicas de atención al Virus del Papiloma Humano (VPH) y al Cáncer Cervicouterino (CaCu) en México / Conceptual uses of gender and vulnerability in public policies for the Human Papillomavirus (HPV) and Cervical Cancer in Mexico

RESUMO El Virus del Papiloma Humano (VPH) es un padecimiento de alto impacto a nivel global: más del 80% de las personas con vida sexual activa lo adquirirá en algún momento. La prevalencia y estragos es mayor en mujeres, pues este virus puede derivar en Cáncer Cervicouterino (CaCu). Desde hace tres décadas, ante el llamado de atención de muchas feministas, organismos de salud internacionales y gobiernos de muchos países han incorporado la perspectiva de género en la atención de estos y otros padecimientos de la salud sexual donde se ha destacado la noción de vulnerabilidad. El objetivo de este artículo es analizar, desde una perspectiva feminista, cuáles son los usos conceptuales que se hacen de la dupla género-vulnerabilidad en algunos documentos de políticas públicas para la atención del VPH y el CaCu de la Organización Mundial de la Salud, la Organización Panamericana de la Salud y la Secretaría de Salud mexicana. A través de un análisis textual de estos documentos, es señalado que el uso conceptual de la vulnerabilidad a la que están expuestas las mujeres por mandatos de género requiere ser vislumbrado desde ópticas que permita reconocer su agencia. Asimismo, se destaca la relevancia de incorporar a los varones a las políticas públicas de atención a estos padecimientos.

ABSTRACT The Human Papillomavirus (HPV) currently represents one of the most relevant sexual health problems worldwide, since at least, 80% of the sexually active population might acquire it at any time. Prevalence and injuries are more present among women, where this virus might cause cervical cancer. From three decades ago, several international health organizations as well as countries have adopted a feminist agenda at incorporating gender perspective to pay attention to these and other women's sexual health issues. The objective of this text is to analyze from a feminist perspective the conceptual uses of gender and vulnerability in some documents written by the World Health Organization, the Pan American Health Organization and the Mexican Health Secretariat for HPV and cervical cancer treatment. Throughout textual analyses to health attention documents, I highlight that these uses of vulnerability that Mexican women are exposed to need perspectives that shed light on women's agency. I also emphasize the necessity to incorporate men to these public policies.

Prevalence of anal intraepithelial lesions in patients with inflammatory bowel disease

Introduction: Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal canal associated with HPV, with a higher prevalence in immunosuppressed individuals. Patients with inflammatory bowel disease (IBD) are at potential risk for their development, due to the use of immunosuppressants and certain characteristics of the disease. Method: This is a prospective, cross-sectional, and interventional study that included 53 patients with IBD treated at a tertiary outpatient clinic, who underwent anal smear for cytology in order to assess the prevalence of AIN and associated risk factors. Results: Forty-eight samples were negative for dysplasia and 2 were positive (4%). Both positive samples occurred in women, with Crohn's disease (CD), who were immunosuppressed and had a history of receptive anal intercourse. Discussion: The prevalence of anal dysplasia in IBD patients in this study is similar to that described in low-risk populations. Literature data are scarce and conflicting and there is no evidence to recommend screening with routine anal cytology in patients with IBD. Female gender, history of receptive anal intercourse, immunosuppression and CD seem to be risk factors. (AU)

Virus del papiloma humano (VPH) y cáncer / Human papillomavirus (HPV) and cancer

Cada año, más de medio millón de mujeres en el mundo son diagnosticadas con cáncer cervical, usualmente asociado a la infección por virus del papiloma humano (VPH) de alto riesgo. Aunque la mayoría de las infecciones por VPH se resuelven dentro de un término menor de 2 años, algunos tipos virales, en particular el VPH16, pueden persistir por décadas y originar diferentes tipos de cáncer, siendo el cervical el más común. La historia natural de la infección por VPH de alto riesgo y el periodo prolongado en que ocurre su progresión, permite la prevención de la enfermedad. La infección por VPH de alto riesgo que evoluciona a cáncer incluye varios procesos como la integración del genoma viral, la división celular incontrolada, y la participación de cambios celulares y epigenéticos. La prueba de citología convencional que se viene practicando para la tamización hace más de 50 años continúa teniendo vigencia, especialmente en países de ingresos bajos y medios, pero está siendo reemplazada por otros métodos como las pruebas moleculares que detectan directamente la presencia del virus, con mayor efectividad como prueba de tamización. En 2014, el Ministerio de Salud y Protección Social de Colombia desarrolló una guía de práctica clínica para la detección y manejo de lesiones premalignas de cuello uterino, en la cual se recomienda la prueba de ADN-VPH para la tamización inicial en las mujeres mayores de 30 años. Hasta el momento se han encontrado resultados positivos con la implementación de la prueba, no obstante, se requieren estudios adicionales que confirmen estos hallazgos, dada su importancia en el control de la morbilidad y mortalidad asociadas a la infección

Each year, more than half a million women in the world are diagnosed with cervical cancer, usually associated with high-risk human papillomavirus (HPV) infection. Although most HPV infections resolve within 2 years, some viral types, particularly HPV16, can persist for decades and cause different types of cancer, being the cervical type the most common. The natural history of high-risk HPV infection and the prolonged period in which its progression occurs, allows for the prevention of the disease. High-risk HPV infection that progresses to cancer includes several processes such as viral genome integration, uncontrolled cell division, and the participation of cellular and epigenetic changes. The conventional Pap smear test that has been practiced as a screening method for more than 50 years continues to be used, especially in low- and middle-income countries, but it is being replaced by other methods such as molecular tests that directly detect the presence of the virus, with greater effectiveness as a screening test. In 2014, the Ministry of Health and Social Protection of Colombia developed a clinical practice guide for the detection and management of premalignant cervical lesions, in which the DNA-HPV test is recommended for initial screening in women over 30 years. So far, positive results have been found with the implementation of the test, however, additional studies are required to confirm these findings given its importance in controlling the morbidity and mortality associated with the infection

Prevalencia de los genotipos de HPV en lesiones pre invasoras de alto grado de malignidad y cáncer de cuello uterino en la población del Hospital de Clínicas: Montevideo-Uruguay / Prevalence of HPV genotypes in cervical high risk intraepithelial lesions and cervical cancer in the population of Hospital de Clínicas: Montevideo-Uruguay / Prevalência de genótipos de HPV em lesões pré-invasivas com alto grau de malignidade e câncer de colo do útero na população do Hospital de Clínicas: Montevidéu, Uruguai

El Cáncer de Cuello Uterino (CCU) es un problema de Salud pública a nivel mundial. Su indiscutible asociación con el Virus del papiloma humano (HPV) hace necesario su estudio. El objetivo de este trabajo, es conocer la prevalencia de los diferentes genotipos de HPV, en lesiones pre invasoras de alto grado de malignidad (HSIL) y/o cáncer de cuello uterino. Material y Métodos: Todas las Mujeres que fueron derivadas a pol de TGI del H Clínicas entre enero del 2011 y diciembre de 2012, por un PAP sospechoso de lesión y en las que se confirmó luego un HSIL o cáncer cervical fueron tipificadas. Se recabaron datos de edad, tipo de lesión y genotipificación. La extracción de ADN viral se realizó a partir de muestras cervico vaginales conservadas en medio de transporte comercial (Sacace) mediante el kit QIAamp DNA Mini Kit (QIAGEN). Se buscaron 14 genotipos de alto riesgo. Resultados: Se tipificaron 75 pacientes, 19 con CCU y 56 con HSIL. El HPV 16 fue el más prevalente en un 61,5 % para las infecciones únicas y en un casi 100 % para las múltiples y un 60% para el total de las lesiones, seguido en prevalencia por los HPV 31,33 y 45. El HPV 18 fue muy poco prevalente. Conclusiones: En esta muestra, la prevalencia del HPV 16 está acorde con las publicaciones nacionales siendo el más frecuente. El HPV 18 tiene muy baja prevalencia siendo 2 casos en 75, siempre en infecciones múltiples.

Cervical Cancer (CC) is a public health problem worldwide. Its indisputable association with the Human Papilloma Virus (HPV) makes its study necessary. The objective of this work is to know the prevalence of the different HPV genotypes, in pre-invasive high-grade malignant lesions (HSIL) and / or cervical cancer. Material and Methods: All women who were referred to Low genital tract service in the Hospital de Clinicas between January 2011 and December 2012, for a PAP suspected of injury and in which HSIL or cervical cancer was later confirmed were typified. Data on age, type of lesion and genotyping were collected. The viral DNA extraction was carried out from cervico-vaginal samples preserved in commercial transport medium (Sacace) using the QIAamp DNA Mini Kit (QIAGEN). 14 high-risk genotypes were searched. Results: 75 patients were typified, 19 with CCU and 56 with HSIL. HPV 16 was the most prevalent in 61.5% for single infections and almost 100% for multiple infections and 60% for all lesions, followed in prevalence by HPV 31,33 and 45. The HPV 18 was very rare. Conclusions: In this sample, the prevalence of HPV 16 is in accordance with national publications, being the most frequent. HPV 18 has a very low prevalence, being 2 cases in 75, always in multiple infections.

O câncer cervical é um problema de saúde pública em todo o mundo. E um câncer com uma ligação comprovada com o vírus do papiloma humano. O objetivo é conhecer a prevalência dos diferentes genótipos do HPV em mulheres que apresentam neoplasias pré-invasivas de alto grau e câncer de colo do útero, que foram tratadas e diagnosticadas no Hospital de Clínicas entre janeiro de 2011 e dezembro de 2012. Material e Métodos: o estudo foi realizado em 75 pacientes do Hospital de Clinicas, com diagnóstico histológico de Câncer Cervical e lesões intraepiteliais de alto grau para as quais foi realizado o tipageme do HPV alto risco. Resultados: 75 pacientes foram tipificados, 19 com CCU e 56 com HSIL. O HPV 16 foi o mais prevalente em 61,5% para infecções únicas e quase 100% para infecções múltiplas e 60% para todas as lesões, seguido em prevalência pelo HPV 31,33 e 45. O HPV 18 era muito raro. Conclusões: Nesta amostra, a prevalência do HPV 16 está de acordo com as publicações nacionais, sendo a mais frequente. O HPV 18 tem prevalência muito baixa, sendo 2 casos em 75, sempre em infecções múltiplas.

Vacunas terapéuticas del virus del papiloma humano: revisión de la evidencia actual / Therapeutic vaccines of the human papilloma virus: current evidence review

Resumen: OBJETIVO: Evaluar la inmunogenicidad de los distintos tipos de vacunas terapéuticas y de su efecto en las lesiones causadas por el virus del papiloma humano (VPH) después de su aplicación. Además, analizar los estudios de seguridad y las perspectivas de las vacunas terapéuticas contra el VPH. METODOLOGÍA: Estudio retrospectivo efectuado mediante la búsqueda bibliográfica sistemática en la base de datos PubMed, sin restricción de fecha de publicación. Criterio de inclusión: ensayos clínicos aleatorizados (metanálisis y revisiones sistemáticas). Criterios de exclusión: ensayos clínicos en fase preclínica del desarrollo y publicaciones en idiomas distintos al inglés o español. RESULTADOS: Se seleccionaron 30 artículos publicados entre 2000 y 2020. Entre ellos, 5 ensayos clínicos aleatorizados con vacunas terapéuticas que ya han finalizado o aún están en estudio. Las 25 publicaciones restantes incluyen: metanálisis y revisiones sistemáticas de aspectos seleccionados con objetivos primarios y secundarios. CONCLUSIONES: Las vacunas terapéuticas contra VPH se encuentran en fase experimental; hasta ahora se han conseguido resultados prometedores con algunas de ellas. Si bien existen distintos tipos de vacunas terapéuticas, los mejores resultados se han conseguido con las basadas en ADN. Las vacunas VGX-3100 y TS, en fase III, han demostrado diferencias significativas en el aclaramiento viral y la regresión de las lesiones de alto grado en pacientes vacunadas. Una vacuna terapéutica efectiva tendría una repercusión inmediata en la morbilidad y mortalidad por lesiones asociadas al virus.

Abstract: OBJECTIVE: To assess the immunogenicity of different types of therapeutic vaccines and their effect on human papillomavirus (HPV) lesions after application. In addition, to analyze the safety studies and prospects of therapeutic HPV vaccines. METHODOLOGY: Retrospective study based on a systematic literature search of the PubMed database, with no publication date restrictions. Inclusion criteria: randomized clinical trials (meta-analyses and systematic reviews). Exclusion criteria: clinical trials in the pre-clinical phase of development and publications in languages other than English or Spanish. RESULTS: 30 articles published between 2000 and 2020 were selected. Among them, 5 randomized clinical trials with therapeutic vaccines that have already been completed or are still under study. The remaining 25 publications include: meta-analyses and systematic reviews of selected aspects with primary and secondary objectives. CONCLUSIONS: Therapeutic HPV vaccines are in the experimental phase; so far promising results have been achieved with some of them. Although different types of therapeutic vaccines exist, the best results have been achieved with DNA-based vaccines. The VGX-3100 and TS vaccines, in phase III, have demonstrated significant differences in viral clearance and regression of high-grade lesions in vaccinated patients. An effective therapeutic vaccine would have an immediate impact on morbidity and mortality from virus-associated lesions.

Detection of human papillomavirus in oropharyngeal squamous cell carcinoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) etiologically attributed to oncogenic human papillomavirus (HPV). Reliable and accurate identification and detection tools are important as the incidence of HPV-related cancer is on the rise. Several HPV detection methods for OPSCC have been developed and each has its own advantages and disadvantages in regard to sensitivity, specificity, and technical difficulty. This review summarizes our current knowledge of molecular methods for detecting HPV in OPSCC, including HPV DNA/RNA polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), p16 immunohistochemistry (IHC), and DNA/RNA in situ hybridization (ISH) assays. This summary may facilitate the selection of a suitable method for detecting HPV infection, and therefore may help in the early diagnosis of HPV-related carcinoma to reduce its mortality, incidence, and morbidity.

Detection of human papillomavirus in oropharyngeal squamous cell carcinoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) etiologically attributed to oncogenic human papillomavirus (HPV). Reliable and accurate identification and detection tools are important as the incidence of HPV-related cancer is on the rise. Several HPV detection methods for OPSCC have been developed and each has its own advantages and disadvantages in regard to sensitivity, specificity, and technical difficulty. This review summarizes our current knowledge of molecular methods for detecting HPV in OPSCC, including HPV DNA/RNA polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), p16 immunohistochemistry (IHC), and DNA/RNA in situ hybridization (ISH) assays. This summary may facilitate the selection of a suitable method for detecting HPV infection, and therefore may help in the early diagnosis of HPV-related carcinoma to reduce its mortality, incidence, and morbidity.

Evolução da técnica de PCR: sua contribuição no diagnóstico da infecção por HPV / Evolution of techinique PCR: its contribution to infection diagnosis by HPV

Introdução: a reação em cadeia da polimerase (PCR) é a técnica de biologia molecular mais utilizada na detecção viral, principalmente em situações onde a quantidade de DNA disponível é pequena. O papilomavírus humano (HPV) representa um dos mais graves problemas de saúde pública e está associado ao câncer do colo do útero, especialmente em países em desenvolvimento, como o Brasil, que desde 2009 já apresentava 40 mil novos casos por ano. Objetivo: descrever a evolução da PCR e sua contribuição no diagnóstico do HPV. Metodologia: realizou-se uma revisão de literatura a partir de publicações disponíveis em base de dados eletrônicos, como Science Direct, SciELO, Pubmed, Instituto Nacional do Câncer e Ministério da Saúde do Brasil, nos últimos cinco anos. Resultados: dentre as técnicas citadas nesta revisão de literatura, todas têm alta relevância na detecção de genotipagem do HPV, embora a escolha quanto ao melhor desempenho fique a critério do pesquisador. A técnica de Nested PCR demonstra ser a mais vantajosa na detecção do vírus, pelo fato de ter uma maior sensibilidade, em comparação com as demais. Conclusão: a técnica PCR possui alta sensibilidade (90-100%) e apresenta 92,8 a 100% de especificidade, sendo padrão ouro para a detecção de DNA do HPV, em amostras citológicas do câncer de colo do útero. Assim, os dados obtidos permitem constatar que a técnica PCR, utilizada para o rastreamento do HPV, é considerada padrão ouro, tendo maior sensibilidade, especificidade e velocidade de análise, devendo ser o método de escolha para o diagnóstico eficiente do HPV.

Introduction: polymerase chain reaction (PCR) is the most widely used molecular biology technique for viral detection, especially in situations where the amount of available DNA is small. Human papillomavirus (HPV) represents one of the most serious public health problems and is associated with cervical cancer, especially in developing countries such as Brazil that has had 40,000 (forty thousand) new cases a year, since 2009. Objective: to describe the evolution of PCR and its contribution to HPV diagnosis. Methodology: a literature review was conducted from publications available in electronic databases, such as Science Direct, SciELO, Pubmed, National Cancer Institute and Ministry of Health of Brazil, in the last five years. Results: among the techniques cited in this literature review, all have high relevance in the detection of HPV genotyping, although the choice for the best performance is at the discretion of the researcher. The Nested PCR technique proves to be the most advantageous in detecting the virus because it has a higher sensitivity compared to the others. Conclusion: the PCR technique has high sensitivity (90-100%) and presents 92.8 to 100% specificity, being the gold standard for the HPV DNA detection in cytology samples of uterus cervix cancer. Thus, the data obtained show that the PCR technique used for HPV screening is considered the gold standard, having greater sensitivity, specificity and speed of analysis, and should be the method of choice for the efficient diagnosis of HPV.

Research progress on the role and mechanism of miR-155 in the development of oral squamous cell carcinoma / 口腔疾病防治

@#Oral squamous cell carcinoma (OSCC) is the most common oral cancer. Previous studies have found significantly high miR-155 expression in OSCC. However, the mechanism by which miR-155 plays a role in OSCC oncogenesis is not yet clear. This article reviews the function of the relationship between miR-155 and tumors and the potential role of miR-155 in the development of OSCC. A literature review showed that mir-155, as a small carcinogenic RNA, can inhibit CDC73, BCL6, P27Kip1 and other target genes that play a role in cancer inhibition; promote the proliferation, migration and invasion of OSCC cells; and inhibit apoptosis. miR-155 can also be combined with biological factors (Epstein-Barr virus, human papillomavirus) to promote the development of OSCC.

Cáncer orofaríngeo y virus del papiloma humano en cabeza y cuello: relaciones fisiopatológicas y epidemiológicas / Oropharyngeal carcinoma and papiloma virus in head and neck: phisiopathological and epidemiological relations

Resumen El Virus del Papiloma Humano (VPH) es una enfermedad diagnóstico frecuente, transmitida por contacto entre piel y mucosas. Se han descrito múltiples relaciones etiológicas con neoplasias en órganos del sistema genital y reproductor y a nivel de cabeza y cuello. Éste se ha agrupado y caracterizado mediante análisis filogenéticos y en su secuencia de nucleótidos y aminoácidos. EL VPH progresa por las capas de epitelio de piel o mucosa induciendo malignización celular. El diagnóstico se realiza mediante diversas técnicas de PCR o de hibridación in situ. El carcinoma orofaríngeo es una patología neoplásica con una presentación clínica variada. Su asociación a VPH es inmunohistoquímicamente detectable, y se asocia a una presentación más frecuente en jóvenes, en hombres, con una localización anatómica mejor definida, y con una expresión clínica más florida y temprana. Actualmente se ha documentado un incremento en los casos de carcinoma orofaríngeo a pesar del descenso de su principal factor de riesgo; el tabaquismo. Su incidencia y mortalidad continúan siendo relativamente bajas en comparación con otros tumores en cabeza y cuello. Este incremento se ha asociado etiológicamente a la infección de VPH con subtipos de mayor riesgo de malignidad como el VPH 16 y 18. A nivel nacional existen diferencias estadísticas con respecto a los datos foráneos, sin embargo la cantidad de estudios realizados en nuestra población y los sesgos asociados al subregistro de la enfermedad son un factor importante a tomar en cuenta. Es necesario realizar una mayor cantidad de estudios en la población costarricense para determinar el comportamiento real de esta enfermedad y su relación etiológica con el carcinoma de orofaringe en nuestro país.

Abstract The Human Papilloma Virus (HPV) is a frequently diagnosed sexually transmitted disease, transmitted by contact between skin and mucous membranes. There are multiple etiological relationships between HPV infections and neoplasms in organs of the reproductive and genital system and at head and neck. Those belonging to HPV have been grouped and characterized by phylogenetic analysis and by its sequence of nucleotides and amino acids. HPV progresses through the layers of skin or mucosal epithelium inducing malignant transformation in these cells. The diagnosis of this infection is performed using various techniques of PCR and in situ hybridization. Oropharyngeal carcinoma is a neoplastic disease with a varied clinical presentation. Its association with HPV is detectable by immunohistochemic methods. It's also associated more frequent with young people, men, presentation with a better defined anatomic location and an earlier clinical expression. Currently it has been documented an increase in cases of oropharyngeal carcinoma despite the fall of their main risk factor; smoking. Its incidence and mortality continue to be relatively low in comparison with other head and neck tumors. This increase has etiologically been associated with HPV infection; and with subtypes of increased risk of malignancy such as HPV 16 and 18; as with changes in the behavior of the disease. National statistics differ from the foreign data, however the low amount of studies in our population and the biases associated with underreporting of the disease are an important factor to take into account. It is necessary to perform a greater number of studies in the Costa Rican population to determine the actual behavior of this disease and its etiological relation to carcinoma of the oropharynx.

Infección por el virus del papiloma humano en adolescentes y adultas jóvenes / Infection with human papillomavirus in adolescents and young adults

La infección por el virus del papiloma humano (VPH) se encuentra asociada a diferentes lesiones que van desde benignas hasta malignas. Los mayores picos de prevalencia de dicha infección se encuentran en mujeres entre los 15-24 años de edad. El objetivo es realizar una revisión de la literatura científica actual sobre la prevalencia de la infección por el VPH en mujeres menores de 25 años a nivel mundial. Para este fin se utilizaron las bases de datos, PubMed, MedLine, BioMed Central y SciELO. En este grupo etario se observó una alta frecuencia de infección por VPH, así como un elevado riesgo de desarrollar lesiones premalignas. La edad de la primera relación sexual, el número de compañeros sexuales, el tipo de VPH infectante y la persistencia viral, mostraron ser factores de riesgo significativos para la transformación maligna. La prevención, como un método para evitar la infección por estos virus, es un arma promisoria en la lucha contra el cáncer cérvico uterino(AU)

Human papilloma virus (HPV) infection is associated with different lesions ranging from benign to malignant. The highest prevalence peaks of this infection are found in women between 15-24 years of age. To conduct a review of the current scientific literature on the prevalence of HPV infection in women under 25 years of age worldwide. Databases, PubMed, MedLine, BioMed Central and SciELO were used for this purpose. In this age group a high frequency of HPV infection was observed, as well as a high risk of developing premalignant lesions. The age of first intercourse, the number of sexual partners, the type of HPV infection and viral persistence, were significant risk factors for malignant transformation. Prevention, as a method to avoid infection by these viruses, is a promising weapon in the fight against cervical cancer(AU)

Regulation of HPV transcription

Human papillomavirus infection is associated with the development of malignant and benign neoplasms. Approximately 40 viral types can infect the anogenital mucosa and are categorized into high- and low-risk oncogenic human papillomavirus, depending on their association with the development of cervical carcinoma. High-risk human papillomavirus 16 and 18 are detected in 55% and 15% of all invasive cervical squamous cell carcinomas worldwide, respectively. Low-risk human papillomavirus 6 and 11 are responsible for 90% of genital warts and are also associated with the development of recurrent respiratory papillomatosis. Human papillomavirus preferentially infects mitotic active cells of the basal layer from both mucosal and cutaneous epithelium through microabrasions. The viral life cycle synchronizes with the epithelial differentiation program, which may be due, in part, to the binding of differentially expressed cellular transcription factors to the long control region throughout the various epithelial layers. This review aimed to summarize the current knowledge regarding the mechanisms by which viral gene expression is regulated and the influence of human papillomavirus heterogeneity upon this phenomenon. A better understanding of the regulatory mechanisms may elucidate the particularities of human papillomavirus-associated pathogenesis and may provide new tools for antiviral therapy.

Expressions of HPV16/18 E6 protein and its clinical, predictive value of cervical intraepithelial neoplasia / 上海交通大学学报（医学版）

Objective: To investigate the clinical significance and predictive value of human papillomavirus (HPV) 16/18 E6 protein in the different cervical intraepithelial neoplasia. Methods: The expression of HPV16/18 E6 in 10 normal cervical tissues, 33 cervical intraepithelial neoplasia I (CIN I ), 31 CIN II-III, 30 cervical cancers was detected by immunohistochemistry, explored the expression difference and the relationship with the clinicopathological characteristics of cervical cancer and the prognosis of different CIN. Results: The positive expression rates of HPV16/18 E6 in normal cervical tissues, CIN I, CIN II-III and cervical cancer group were up-regulated (χ2=19.82, P=0.000). HPV16/18 E6 increased positive expression rates in the low grade and the big size tumors of cervical cancer tissues were detected (P=0.033, P=0.011). There were positive correlations between the overexpression and the pathological grade, tumor size, poor prognosis of cervical cancers respectively (r=0.456, P=0.011; r=0.578, P=0.000; r=0.645, P=0.000). The sensitivity, specificity, and diagnostic accuracy rates of HPV16/18 E6 positive expression to the progression of CIN I, CIN II-III and cervical cancer were respectively 100.00%, 62.50%, 43.75%; 96.77%, 91.30%, 92.86%; 96.97%, 83.87%, 66.67%. Conclusion: HPV16/18 E6 overexpression plays an important role in the generation, development and the poor prognosis of cervical cancer. HPV16/18 E6 has a good predictive value for the prognosis and hierarchical management of cervical diseases.