High-risk human papillomavirus negative cervical lesions in the cervical cancer screening population / 中国医师杂志

Objective:To investigate the incidence of high-risk human papillomavirus (hrHPV) negative cervical lesions in the screening population, and based on this, to preliminarily evaluate the potential harm (missed diagnosis) and benefits (reduced colposcopy referral) of HPV primary screening compared to combined screening so as to provide reference for the selection of cervical cancer primary screening methods.Methods:This study was a single center cross-sectional study. Women who underwent joint screening [hrHPV typing test combined with cervical liquid based cytology test (LCT)] at the Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 1, 2018 to December 31, 2019 were included in the cervical cancer screening. The proportion of hrHPV negative cytological abnormalities and cervical lesions in the population was analyzed and the theoretical colposcopy referral rate of the combined screening and HPV initial screening protocol was calculated. In the population with cervical pathological results, the number of colposcopy examinations required for the diagnosis of cervical intraepithelial neoplasia grade 2 and above (CIN2+ ) was calculated.Results:A total of 35 321 screened women were included. The overall incidence of hrHPV infection, LCT abnormalities and severe LCT abnormalities in the population was 17.13%(6 051/35 321), 18.07%(6 384/35 321), and 3.97%(1 402/35 321), respectively. The negative rate of hrHPV in women with severe cervical cytology abnormalities was as high as 51.28%(719/1 402), and in CIN2+ lesions diagnosed by cervical biopsy, hrHPV negative accounted for 7.15% (49/685). The theoretical colposcopy referral rates for combined screening and initial HPV screening were 11.28%(3 985/35 321) and 8.33%(2 943/35 321), respectively, with an average diagnosis of CIN2+ requiring 3.51 and 2.81 colposcopy examinations, respectively.Conclusions:In the opportunistic screening population, the proportion of hrHPV negative CIN2+ lesions cannot be ignored, and the HPV initial screening strategy may cause missed diagnosis of these lesions. However, compared to combined screening, HPV initial screening has the potential to improve the efficiency of colposcopy. These results suggest that we should carefully choose the HPV initial screening plan.

Screening for cervical cancer and diversion of abnormal screening results / 中国医师杂志

Cervical cancer is still a serious threat to the health of women in China. The current strategy is a three-level prevention strategy, among which the diversion of screening and screening abnormalities in the secondary prevention is an important link in preventing cervical cancer. For more than 20 years, China has implemented diversified screening methods such as cytological examination, high-risk human papillomavirus (HPV) testing, and naked eye screening. With the discovery that high-risk HPV infection is closely related to the occurrence of cervical cancer, the screening method for cervical cancer has shifted from cytological examination to HPV testing as the preferred screening method. This article introduces the advantages and disadvantages of high-risk HPV testing and cytological examination as screening methods, and proposes the issues that need to be paid attention to in screening; The principle of diverting screening abnormalities was proposed, and it was proposed that in the process of diverting, individualized and refined management principles should be implemented for screening abnormality projects based on the patient′s age and fertility requirements.

Cervical Cancer Screening with HPV Testing: Updates on the Recommendation / Rastreamento do câncer do colo de útero com teste de HPV: Atualizações na recomendação

Abstract The present update is a reassessment of the 2018 'Guidelines for HPV-DNA Testing for Cervical Cancer Screening in Brazil' (Zeferino et al.)9, according to the changes observed in new international guidelines and knowledge updates. The most relevant and recent guidelines were assessed. Questions regarding the clinical practice were formulated, and the answers considered the perspective of the public and private sectors of the Brazilian health system. The review addressed risk-based strategies regarding age to start and stop screening, the use of cytology and colposcopy to support management decisions, treatment, follow-up strategies, and screening in specific groups, including vaccinated women. The update aims to improve the prevention of cervical cancer and to reduce overtreatment and the misuse of HPV testing.

Resumo Esta atualização é uma reavaliação das "Recomendações para o uso de testes de DNAHPV no rastreamento do câncer do colo do útero no Brasil" (Zeferino et al., 2018),9 de acordo com as mudanças observadas nas novas recomendações internacionais, além das atualizações no conhecimento. As recomendações mais relevantes e recentes foram avaliadas. Questões referentes à prática clínica foram formuladas, e as respostas consideraram a perspectiva do sistema de saúde brasileiro, tanto público quanto privado. Esta revisão abrange estratégias baseadas em risco sobre idade para início e término de rastreamento, o uso da citologia e colposcopia para apoiar as condutas, tratamento, estratégias de seguimento, e rastreamento em grupos específicos, incluindo mulheres vacinadas. Esta atualização tem o objetivo de melhorar as estratégias de prevenção do câncer do colo de útero e reduzir o supertratamento e o uso incorreto dos testes de HPV.

Cervical cancer screening in low- and middle-income countries: A systematic review of economic evaluation studies

Abstract Economic assessments are relevant to support the decision to incorporate more cost-effective strategies to reduce Cervical Cancer (CC) mortality. This systematic review analyzes the economic evaluation studies of CC prevention strategies (HPV DNA-based tests and conventional cytology) in low- and middle-income countries. Medline, EMBASE, CRD, and LILACS were searched for economic evaluation studies that reported cost and effectiveness measures of HPV DNA-based tests for CC screening and conventional cytology in women, without age, language, or publication date restrictions. Selection and data extraction were carried out independently. For comparability of results, cost-effectiveness measures were converted to international dollars (2019). Report quality was assessed using the CHEERS checklist. The Dominance Matrix Ranking (DRM) was used to analyze and interpret the results. The review included 15 studies from 12 countries, with cost-effectiveness analyzes from the health system's perspective and a 3% discount rate. The strategies varied in age and frequency of screening. Most studies used the Markov analytical model, and the cost-benefit threshold was based on the per capita GDP of each country. The sensitivity analysis performed in most studies was deterministic. The completeness of the report was considered sufficient in most of the items evaluated by CHEERS. The Dominance Interpretation (DRM) varied; in 6 studies, the HPV test was dominant, 5 studies showed a weak dominance evaluating greater effectiveness of the HPV test at a higher cost, yet in 2 studies conventional cytology was dominant. Although the context-dependent nature of economic evaluations, this review points out the challenge of methodological standardization in the analytical models.

Characteristics of cervical lesions in 1 080 patients with abnormal colposcopic biopsies of TCT and HPV double screening in Shihezi region / 中国医师杂志

Objective:To explore the characteristics of cervical lesions in female patients in the Shihezi region of Xinjiang in the past two years and provide guidance for clinical work and local cervical cancer screening.Methods:The clinicopathological data and characteristics of 1 080 patients with abnormal double screening of human papilloma virus (HPV) and cervical exfoliative cell test (TCT) and vaginal mirror cervical tissue biopsy in the gynecology department of the First Affiliated Hospital of Medical College of Shihezi University from May 2017 to March 2019 were analyzed retrospectively. The influencing factors of cervical lesions were analyzed by logistic regression.Results:(1) Uneducated [odds ratio ( OR)=2.267], irregular vaginal bleeding ( OR=3.275) and number of sexual partners ≥3 ( OR=3.052) were independent risk factors for cervical lesions. (2) Cervical intraepithelial neoplasia (CIN) was detected most frequently in the 30-39 age group (57.54%), and cervical cancer was detected most frequently in the ≥60 age group (14.15%), followed by the 40-49 age group (2.20%). (3) The proportion of HPV positive and the positive rate of high-risk HPV16/18 in the 40-49 age group were the highest, 33.18% and 39.38% respectively. There was no statistically significant difference in HPV viral load between the different age groups ( P>0.05). (4) The detection rates of CIN3 and cervical cancer were higher in the HPV16/18-positive group than in the HPV-positive and TCT≥atypical squamous epithelial cells of undermined significance (ASC-US) group (18.34% vs 11.33%, 4.30% vs 1.82%), with statistically significant difference (all P<0.05), respectively. The detection rate of CIN2 was higher in the high-load group (28.44%) than in the medium-load group (25.32%) and the low load group (15.79%). (5) The detection rate of CIN3 in the HPV-positive TCT for the ASC-US populations was significantly higher in the HPV16/18-positive group than in the other subtypes of HPV-positive group (21.43% vs 8.33%, P<0.05). Conclusions:During cervical cancer screening in Shihezi region, we should strengthen the publicity of elderly women and uneducated people. CIN and cervical carcinoma in Shihezi region are closely associated with high-risk HPV infection, especially HPV16/18 infection. HPV-positive age is mainly concentrated in the age group of 40-49 years, and the detection rate of CIN and cervical cancer is the highest in the age group of 30-39 years and ≥60 years, respectively. The detection rate of ≥CIN2 in HPV16/18 fraction and high viral load population is higher than that of other HPV subtypes positive and low to medium load populations. How to effectively shunt HPV positive TCT is an important problem in ASC-US population, which needs further research.

Intracellular free heme concentration detection versus high-risk human papillomavirus detection in screening cervical cancer and precancerous lesions / 中国基层医药

Objective:To compare the application value of intracellular free heme concentration (FH) detection and high-risk human papillomavirus (HPV) detection in screening cervical cancer and precancerous lesions.Methods:A total of 238 patients with cervical abnormalities who received FH and HPV detection in Huainan First People's Hospital, China from October 2017 to October 2019 were included in this study. Taking liquid-based ThinPrep cytologic test (TCT) results and pathological biopsy results as gold standard, the diagnostic value of FH detection and TCT detection for cervical cancer and precancerous lesions were compared.Results:TCT results revealed normal/inflammatory diagnosis in 97 patients, and atypical squamous cells of undetermined significance (ASCUS) or higher grade diagnosis in 141 patients. Pathological biopsy results reported cervical intraepithelial neoplasia (CIN) grade II or above in 70 out of the 141 patients. The detection rate of FH detection for CIN grade II or above cervical lesions was 92.86% (65/70) and the detection rate of high-risk HPV detection was 95.71% (67/70). The sensitivity and specificity of FH detection in the screening CIN grade II or above cervical lesions were 82.86% (58/70) and 85.92% (60/70), respectively and they were 94.29% (66/70) and 98.59% (69/70) for high-risk HPV detection. There were significant differences in diagnostic sensitivity and specificity between FH dection and high-risk HPV detection ( χ2 = 4.52, 10.25, both P < 0.05). Conclusion:High-risk HPV detection is of high application value in the diagnosis of cervical cancer and precancerous lesions. It has higher sensitivty and specificity in screening cervical cancer and precancerous lesions than FH detection. But FH detection is simpler, more economical and easier to use and is more suitable for large-scale screening of cervical cancer and precancerous lesions than high-risk HPV detection.

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.

Implementación de la nueva guía práctica clínica para la detección y manejo de lesiones precancerosas de cuello uterino en mujeres de la ciudad de Cali, Colombia / Implementation of the new clinical practice guideline for the detection and management of precancerous lesions of the cervix in women from the city of Cali, Colombia

Objetivos del trabajo: Se determinaron los porcentajes de las lesiones precancerosas de cuello uterino en un grupo de mujeres diagnosticadas positivas por la prueba ADN-VPH. Materiales y métodos: El presente estudio es un análisis exploratorio descriptivo transversal de una base de datos con resultados de las pruebas de ADN-VPH (genotipo y tipo de infección), citología y colposcopia, realizadas en 58 mujeres de 30 años o más, para el periodo de octubre del 2018 a febrero del 2019. Resultados: De las 58 mujeres positivas para la prueba ADN-VPH, el 57% (n=33) fueron positivas para la prueba citológica cervical. De este grupo de mujeres fueron diagnosticadas negativas para LEI el 21% (n=7); para LEI-BG el 33% (n=11); y para LEI-AG el 45% (n=15) mediante la prueba de colposcopia. El VPH-16 mostró la mayor frecuencia relativa de detección en las LEI-AG con un 46,7% (n=7). Igualmente, los genotipos que cubre la vacuna Gardasil_4 fueron identificados en mayor porcentaje en las LEI-AG en comparación con los otros tipos histopatológicos diagnosticados, siendo esta asociación estadísticamente significativa, valor de p = 0,033. Conclusiones: La implementación de la nueva guía de práctica clínica para la detección y manejo de lesiones precancerosas de cuello uterino muestra resultados satisfactorios, siendo concordante la detección de ADN-VPH, con la identificación de anormalidades citológicas e histopatológicas, permitiendo la identificación precoz de mujeres en riesgo de desarrollar cáncer cervical.

Objectives of the study: To determine the percentages of precancerous lesions in the cervix in a group of women with positive diagnostic to the DNA-HPV test. Materials and methods: The present study is a cross-sectional exploratory analysis of a database with information on the results of DNA-HPV tests (genotype and type of infection), cytology and colposcopy, carried out on 58 women aged 30 or older, for the period from October 2018 to February 2019. Results: Of the 58 women positive for the DNA-HPV test, 57% (n=33) were positive for the cervical cytology test. Of this group of women, 21% (n=7) were diagnosed LEI-negative; for LEI-BG 33% (n=11); and for LEI-AG, 45% (n=15) using the colposcopy test. HPV-16 has a higher detection frequency in the LEI-AG with 46.7% (n=7). Likewise, the genotypes that cover the Gardasil_4 vaccine were members in a greater percentage in the LEI-AG in comparison with other diagnosed histopathological types, this association being statistically significant, value of p = 0.033. Conclusions: The implementation of the new clinical practice guideline for the detection and management of precancerous lesions of the cervix shows satisfactory results, the DNA-HPV detection being consistent, with the identification of cytological and histopathological abnormalities, allowing the early identification of women at risk to develop cervical cancer.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts: • Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia. • Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method. • The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years. • Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology / 부인종양

Current Status of and Perspectives on Cervical Cancer Screening in Korea

Since the introduction of the Papanicolaou (Pap) smear system in 1943, cervicovaginal cytology has been used as a standard screening test for cervical cancer. The dissemination of this test contributed to reductions of the incidence and mortality of cervical cancer worldwide. In Korea, regular health check-ups for industrial workers and their family members were introduced in 1988 and were performed as part of the National Cancer Screening Program in 1999. As a result, the incidence of cervical cancer in Korea has been steadily decreasing. However, about 800 cases of cervical cancer-related deaths are reported each year due to false-negative test results. Hence, new screening methods have been proposed. Liquid-based cytology (LBC) was introduced in 1996 to overcome the limitations of conventional Pap smears. Since then, other LBC methods have been developed and utilized, including the human papilloma virus test—a method with higher sensitivity that requires fewer screenings. In this study, we review current issues and future perspectives related to cervical cancer screening in Korea.

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.

Genotipificación del Virus de Papiloma Humano en mujeres de la comuna norte de Bucaramanga / Genotypification of Human Papilloma Virus in women of the comuna Norte de Bucaramanga

Resumen Introducción: La infección persistente con Virus de Papiloma Humano de alto riesgo es causa necesaria para la aparición de cáncer de cérvix. Objetivo: Caracterizar molecularmente los genotipos circulantes de Virus de Papiloma Humano en población de la zona Norte de Bucaramanga. Métodos: Estudio de corte transversal en mujeres de 35 a 65 años con riesgo ≥3 puntos para desarrollar cáncer de cérvix determinado por una encuesta estandarizada. En una muestra cervico-vaginal por autotoma se realizaron pruebas moleculares por tecnología HPV Direct Flow CHIP. Resultados: Se encuestaron 810 mujeres, de éstas 435 (53,7%) se realizaron auto-toma por el riesgo presentado. La mediana de edad fue de 47,3 años (RIQ 41-53 años). Casi la totalidad de la población reside en estrato 1 y 2 (98,8%) y en su mayoría son del régimen subsidiado (87,2%). La prevalencia de infección fue de 10,6% (IC 95%: 7,8 - 13,8), para genotipos de alto riesgo fue de 3,9% (IC 95%: 2,3 - 6,2), de bajo riesgo de 3,5% (IC 95%: 1,4 - 5,6) y para genotipo indeterminado de 1,9%. El genotipo de alto riesgo más común fue VPH-59 y de bajo riesgo fue VPH-62/81. Hubo coinfección con genotipos alto/bajo riesgo en cinco mujeres y coinfección con dos genotipos de bajo riesgo en una mujer. Conclusión: la prevalencia de infección por Virus de Papiloma Humano en mujeres que habitan en zonas vulnerables de Bucaramanga es menor a la reportada en Bogotá y Cali (14,9% y 13%, respectivamente). No se encontró predominio de ningún genotipo de alto riesgo en particular.

Abstract Introduction: Persistent infection with high-risk Human Papilloma Virus is a necessary cause for the appearance of cervical cancer. Objective: Molecularly characterize circulating genotypes of Human Papilloma Virus in population of the north of Bucaramanga. Methods: Cross-sectional study in women aged from 35 to 65 years with risk ≥3 points for develop cervical cancer determined by a standardized survey. In a cervico-vaginal self-sampling probe a molecular test was performed by HPV Direct Flow CHIP technology. Results: 810 women were interviewed, of these 435 (53.7%) performed self-sampling due to the risk calculated. The median age was 47.3 years (RIQ 41-53 years). Almost the entire population resides in poor conditions (stratum1 and 2) (98.8%) and most of them are from the Colombian subsidized social security system (87.2%). The prevalence was 10.6% (CI 95%: 7.8 - 13.8), for high risk genotypes it was 3.9% (CI 95%: 2.3 - 6.2), low risk of 3.5% (CI 95%: 1.4 - 5.6) and for indeterminate genotype of 1.9%. HPV-59 was the most common high-risk genotype and HPV-62/81 was a low-risk genotype. There was coinfection with high risk / low risk genotypes in five women and coinfection with two low risk genotypes in a woman. Conclusion: The prevalence of infection by Human Papilloma Virus in women living in vulnerable areas of Bucaramanga is lower than that reported in Bogotá and Cali (14.9% and 13%, respectively). No predominance of any particular high-risk genotype was found.

Detection of High-Risk Human Papillomavirus in Cervix Sample in an 11. 3-year Follow-Up after Vaccination against HPV 16/18 / Detecção de papilomavírus humano de alto risco em amostras de colo uterino em 11. 3 anos de acompanhamento após vacinação contra HPV 16/18

Abstract Purpose the aim of this study was to evaluate the pattern of human papillomavirus (HPV) detection in an 11.3-year post-vaccination period in a cohort of adolescent and young women vaccinated or not against HPV 16/18. Methods a subset of 91 women from a single center participating in a randomized clinical trial (2001-2010, NCT00689741/00120848/00518336) with HPV 16/18 AS04- adjuvanted vaccine was evaluated. All women received three doses of the HPV vaccine (n = 48) or a placebo (n = 43), and cervical samples were collected at 6-month intervals. Only in this center, one additional evaluation was performed in 2012. Up to 1,492 cervical samples were tested for HPV-DNA and genotyped with polymerase chain reaction (PCR). The vaccine group characteristics were compared by Chi-square or Fisher exact or Mann-Whitney test. The high-risk (HR)-HPV 6-month-persistent infection rate was calculated. The cumulative infection by HPV group was evaluated by the Kaplan-Meier method and the log-rank test. Results the cumulative infection with any type of HPV in an 11.3-year period was 67% in the HPV vaccine group and 72% in the placebo group (p = 0.408). The longitudinal analysis showed an increase of 4% per year at risk for detection of HR-HPV (non-HPV 16/ 18) over time (p = 0.015), unrelated to vaccination. The cumulative infection with HPV 16/18 was 4% for the HPV vaccine group and 29% for the placebo group (p = 0.003). There were 43 episodes of HR-HPV 6-month persistent infection, unrelated to vaccination. Conclusions this study showed themaintenance of viral detection rate accumulating HR-HPV (non-HPV-16-18) positive tests during a long period post-vaccination, regardless of prior vaccination. This signalizes that the high number of HPV-positive testsmay be maintained after vaccination.

Resumo Objetivos avaliar o padrão de detecção do papilomavírus humano (HPV) em um período de 11.3 anos após a vacinação em uma coorte de adolescentes e mulheres jovens vacinadas ou não contra HPV 16/18. Métodos avaliou-se um subgrupo de 91 mulheres de um único centro, participantes de ensaio clínico randomizado (2001-2010, NCT00689741/00120848/00518336) com a vacina contra HPV 16/18 com adjuvante AS04. Todas as mulheres receberam três doses de vacina contra HPV (n = 48) ou placebo (n = 43), e tiveram amostras cervicais coletadas em intervalos de 6 meses. Somente neste centro, uma avaliação adicional foi realizada em 2012. Um total de 1.492 amostras cervicais foram testadas para DNA-HPV e genotipadas com reação em cadeia da polimerase (RCP). As características dos grupos de vacina contra HPV ou placebo foram comparadas pelo teste de Qui-quadrado ou teste exato de Fisher ou teste de Mann-Whitney. A infecção persistente por 6meses pelo HPV de alto risco (AR) foi calculada. A infecção cumulativa por grupo foi avaliada pelo método de Kaplan-Meier e pelo teste log-rank. Resultados a infecção cumulativa com qualquer tipo de HPV em11.3 anos foi de 67% no grupo vacina contra HPV e de 72% no grupo placebo (p = 0,408). A análise longitudinal mostrou um aumento de 4% ao ano no risco de detecção de HR-HPV (não-HPV 16/18) ao longo do tempo (p = 0,015), não relacionado com a vacinação. A infecção cumulativa com HPV 16/18 foi de 4% para o grupo vacina contra HPV e 29% para o grupo placebo (p = 0,003). Houve 43 episódios de infecção persistente por 6 meses por HR-HPV, não relacionados com a vacinação. Conclusões este estudo mostrou a manutenção da taxa de detecção viral, acumulando testes positivos de HR-HPV (não HPV-16-18) durante longo período pósvacinação, independentemente da vacinação prévia. Isto sinaliza que a alta positividade dos testes de HPV pode ser mantida após a vacinação.

Preferencias y satisfacción hacia un programa de tamizaje con pruebas autoadministradas de detección del virus de papiloma humano / Preferences and satisfaction towards a screening program with self-administered human papilloma virus detection tests

Estudio transversal que describe preferencias y satisfacción hacia un programa de tamizaje de cáncer cervical con pruebas rápidas autoadministradas, para la detección del virus de papiloma humano (VPH). De las 2090 usuarias captadas por el programa en Ventanilla Callao-Perú, se seleccionó aleatoriamente a 97 para ser encuestadas. Asimismo, se realizaron entrevistas a mujeres líderes de la comunidad, encargadas de ofrecer las pruebas. El 74,2% de las usuarias se sintió, cuanto menos, satisfecha con el programa. El 68% de las mujeres prefiere la autotoma de la prueba, principalmente por demandar menos tiempo. De las mujeres que prefieren la toma en el centro de salud, el 90,3% lo hace por la seguridad de que la prueba sea realizada correctamente. La inclusión de líderes comunitarias en el programa permitió una buena difusión de la prueba y de los pasos para realizarla.

Cross-sectional study describing preferences and satisfaction towards a cervical cancer screening program with selfadministered rapid tests for the detection of human papillomavirus (HPV). Of 2 090 users picked by the program in Ventanilla Callao - Peru, 97 were randomly selected to be surveyed. In addition, interviews were conducted with women leaders of the community, in charge of providing the evidence. 74.2% of the users felt, at least, satisfied with the program. 68% of women prefer to take the test, mainly by demanding less time. Of women who prefer to take the test at the Health Center, 90.3% do so for the safety of the test being done correctly. The inclusion of community leaders in the program allowed a good diffusion of the test and the steps to carry it out.

Cervical cancer screening: from Pap smear to future strategies / Triagem de câncer do colo uterino: do teste de Papanicolaou a estratégias futuras

ABSTRACT Previously, the screening for detection of cervical cancer was performed by simple cervicovaginal sample collected by the physician whenever the patient attended the medical consultation, and soon it was established as the annual"Pap smear". Since then, an elementary test has evolved into a complex process with multiple algorithms for the identification of invasive disease. The detection of human papillomavirus (HPV) has become part of the new screening recommendations, resulting in major changes in the guidelines. This review intends to emphasize the most important topics that are part of cervical cancer screening, including cervical cytology and HPV detection, and to discuss particular aspects of cervical cancer in Brazil. Despite the great benefits achieved by the cervical cancer screening programs with cytology and HPV test, there are still important issues to be discussed and improved in defining future strategies, including simplicity and possible application in different socioeconomic contexts, definition of the best test or tests to be applied and recommended interval, minimizing possible harms. After the establishment of screening algorithms well defined by leading organizations, management protocols should be disseminated among physicians and patients by education programs.

RESUMO Inicialmente, a triagem para detecção do câncer de colo uterino era feita por meio de uma simples amostra cervicovaginal colhida pelo médico, sempre que o paciente comparecia à consulta médica; logo se estabeleceu como"exame de Papanicolaou" anual. Desde então, um teste elementar evoluiu para um processo complexo, com múltiplos algoritmos para identificação de doença invasiva. A detecção do papilomavírus humano (HPV) tornou-se parte das novas recomendações de triagem, resultando em grandes mudanças nas diretrizes. Esta revisão pretende enfatizar os tópicos mais importantes que fazem parte do rastreamento do câncer de colo do útero, incluindo citologia cervical e detecção do HPV, bem como discutir aspectos particulares do câncer de colo do útero no Brasil. Apesar dos grandes benefícios alcançados pelos programas de rastreamento do câncer de colo uterino por meio do uso da citologia e do teste de HPV, existem ainda pontos importantes a serem discutidos e melhorados na definição de estratégias futuras, como simplicidade e possível aplicação em diferentes contextos socioeconômicos, definição do melhor teste ou testes a serem aplicados e intervalo recomendável, minimizando possíveis danos. Após o estabelecimento de algoritmos de rastreamento bem definidos pelas principais organizações, protocolos de manejo devem ser divulgados entre médicos e pacientes por programas de educação.

HPV detection in floor of mouth squamous cell carcinoma by PCR amplification / Detecção do HPV em carcinoma espinocelular de assoalho de boca por amplificação da PCR

ABSTRACT Introduction: Studies conducted during the last years, using new technologies for viral detection, permit to consider human papillomavirus (HPV) an etiologic factor for cervical cancer. Besides the relation to genital regions, other anatomic sites have been associated with HPV, including head and neck regions. Objectives: To investigate the prevalence of HPV infection in 35 samples from paraffin-embedded tissues using polymerase chain reaction (PCR)-deoxyribonucleic acid (DNA) amplification, and correlate it with demographic, clinical, and morphological factors and prognosis. Materials and methods: All samples were first amplified with human β-globin gene primers. Samples with positive amplification were subjected to HPV-DNA detection with general GP5 and GP6 primers. Results Only 30 samples were amplified for the β-globin gene. No floor of mouth squamous cell carcinoma cases showed amplification of HPV DNA. Discussion: The absence of HPV-DNA amplification does not suggest that this virus is absent from the process of oral carcinogenesis, since the selected sample is not in the risk group for the development of oral cancer associated with HPV infection. Conclusions: No correlation was found between HPV infection and floor of mouth carcinogenesis, however further studies are necessary.

RESUMO Introdução: Estudos realizados durante os últimos anos permitem considerar a infecção pelopapilomavírus humano (HPV) um fator etiológico para o câncer cervical. Apesar da íntima relação desse vírus com as regiões genitais, outras localizações anatômicas têm sido associadas a tal infecção, inclusive as regiões de cabeça e pescoço. Objetivos: Investigar a prevalência da infecção pelo HPV em 35 amostras parafinadas de carcinoma espinocelular de assoalho de boca, utilizando a amplificação da reação em cadeia dapolimerase (PCR) como método de detecção do ácido desoxirribonucleico (DNA) viral, bem como correlacionar aspectos demográficos, clínicos e morfológicos com o prognóstico da doença. Materiais e métodos: Todas as amostras foram inicialmente amplificadas com o primerpara detecção do gene da β-globina humana. As que tiveram amplificação positiva para o gene da β-globina foram então submetidas à detecção do DNA viral com os primers GP5 e GP6. Resultados: Apenas 30 amostras foram amplificadas para o gene β-globin. Nenhuma das amostras de carcinoma de assoalho de boca demonstrou resultado positivo para amplificação do DNA viral. Discussão: Apesar de a influência do vírus na carcinogênese oral não ter sido comprovada devido à ausência de DNA viral nas amostras, a relação não pode ser descartada, uma vez que as amostras selecionadas não se encontravam em grupo de risco para o desenvolvimento de carcinoma espinocelular de boca associado à infecção pelo HPV. Conclusão: Não foi detectada relação entre a infecção pelo HPV e o carcinoma de assoalho de boca, no entanto mais estudos são necessários sobre o tema.

Can human papillomavirus (HPV) genotyping classify non-16/18 high-risk HPV infection by risk stratification? / 부인종양

OBJECTIVE: Infection with high-risk genotypes of human papillomavirus (HR-HPV) is the major cause of invasive cervical cancers. HPV-16 and HPV-18 are known to be responsible for two-thirds of all invasive cervical carcinomas, followed by HPV-45, -31, and -33. Current guidelines only differentiate HPV-16/18 (+) by recommending direct colposcopy for treatment. We tried to evaluate whether there are differences in risk among 12 non-16/18 HR-HPV genotypes in this study. METHODS: The pathology archive database records of 1,102 consecutive gynecologic patients, who had results for cervical cytology and histology and for HPV testing, as determined by HPV 9G DNA chip, were reviewed. RESULTS: Among the 1,102 patients, 346 were non-16/18 HR-HPV (+) and 231 were HPV-16/18 (+). We calculated the odds ratios for ≥cervical intraepithelial neoplasia 2 (CIN 2) of 14 groups of each HR-HPV genotype compared with a group of HR-HPV (–) patients. Based on the odds ratio of each genotype, we divided patients with non-16/18 HR-HPV genotypes (+) into two groups: HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+). The age-adjusted odds ratios for ≥CIN 2 of the HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+) groups compared with a HR-HPV (–) group were 11.9 (95% CI, 7.6 to 18.8; p<0.001) and 2.4 (95% CI, 1.4 to 4.3; p<0.001), respectively, while that of the HPV-16/18 (+) group was 18.1 (95% CI, 11.6 to 28.3; p=0.003). CONCLUSION: The 12 non-16/18 HR-HPV genotypes can be further categorized (HPV-31/33/35/45/52/58 vs. HPV-39/51/56/59/66/68) by risk stratification. The HPV-31/33/35/45/52/58 genotypes might need more aggressive action. Large scale clinical trials or cohort studies are necessary to confirm our suggestion.

Clinical significance of human papillomavirus genotyping / 부인종양

Cervical cancer is the fourth most common cancer in women worldwide, and the human papillomavirus (HPV) is the main causative agent for its development. HPV is a heterogeneous virus, and a persistent infection with a high-risk HPV contributes to the development of cancer. In recent decades, great advances have been made in understanding the molecular biology of HPV, and HPV\'s significance in cervical cancer prevention and management has received increased attention. In this review, we discuss the role of HPV genotyping in cervical cancer by addressing: clinically important issues in HPV virology; the current application of HPV genotyping in clinical medicine; and potential future uses for HPV genotyping.

Comparative study between biopsy and brushing sampling methods for detection of human papillomavirus in oral and oropharyngeal cavity lesions, / Estudo comparativo entre biópsia e escovado na pesquisa do papilomavírus humano em lesões de cavidade oral e de orofaringe

ABSTRACT INTRODUCTION: Many epidemiological studies have suggested that human papillomavirus (HPV), especially type 16, is involved in the genesis of squamous cell carcinoma of the oral cavity and oropharynx, especially in young, non-smoking patients; thus, its detection in lesions in this region is important. OBJECTIVE: To clarify the capacity of the brushing sampling method to detect the presence of HPV in oral or oropharyngeal lesions through polymerase chain reaction (PCR) testing, and to compare the results with those obtained by biopsy. METHODS: Prospective study of adult patients with oral or oropharyngeal lesions assessed by PCR, comparing biopsy specimens with samples obtained by the brushing method. The study was approved by the Research Ethics Committee of the institution. RESULTS: A total of 35 sample pairs were analyzed, but 45.7% of the brushing samples were inadequate (16/35) and, thus, only 19 pairs could be compared. There was agreement of results in 94.7% (18/19) of the pairs, with HPV identified in 16 of them. HPV DNA was detected in 8.6% (3/35) of biopsy and 5.7% (2/35) of brushing samples. CONCLUSION: There was no statistically significant difference between the two methods, but the brushing sampling method showed a higher number of inadequate samples, suggesting that it is an unreliable method for surveillance.

Resumo INTRODUÇÃO: Muitos estudos epidemiológicos indicam a participação do papilomavírus humano, especialmente o tipo 16, na carcinogênese dos tumores espinocelulares das cavidade oral e oro-faríngea, principalmente em jovens e não fumantes, sendo portanto importante sua detecção nas lesões desta região. OBJETIVO: Elucidar a habilidade do escovado em detectar o papilomavírus humano, pela reação em cadeia da polimerase, nas lesões orais e orofaríngeas, comparando os resultados com os obtidos por biópsia. MÉTODO: Estudo prospectivo de pacientes com lesões orais e orofaríngeas, pela reação em cadeia da polimerase, no qual foram pareados os resultados de amostras obtidas por escovado e por biópsia. A pesquisa foi aprovada pelo Comitê de Ética em Pesquisa da instituição. RESULTADO: Foram analisados 35 pares de amostras, porém estavam inapropriadas para análise 45,7% (16/35) das amostras obtidas por escovado, e portanto, somente 19 pares puderam ser comparados. Em 94,7% dos pares houve concordância dos resultados, sendo encontrado o papilomavírus humano − 16 em um destes pares. O ácido desoxirribonucleico do papilomavírus humano foi detectado em 8,6% (3/35) das biópsias e em 5,7% (2/35) dos escovados. CONCLUSÃO: Não houve diferença estatística entre os métodos, mas como houve um grande número de amostras obtidas por escovado inapropriadas, este parece não ser confiável para o rastreamento.