Cervical Cancer Screening with DNA-HPV Testing and Precancerous Lesions Detection: A Brazilian Population-based Demonstration Study / Rastreamento do câncer do colo do útero com teste de DNA-HPV e detecção de lesões precursoras: um estudo de demonstração de base populacional brasileiro

Abstract Objective To evaluate the rates of precancerous lesions, colposcopy referral, and positive predictive value (PPV) by age groups of a population-based screening with DNA-HPV testing. Methods The present demonstration study compared 16,384 HPV tests performed in the first 30 months of the program with 19,992 women tested in the cytology screening. The colposcopy referral rate and PPV for CIN2+ and CIN3+ by age group and screening program were compared. The statistical analysis used the chi-squared test and odds ratio (OR) with 95% confidence interval (95%CI). Results The HPV tests were 3.26% positive for HPV16-HPV18 and 9.92% positive for 12 other HPVs with a 3.7 times higher colposcopy referral rate than the cytology program, which had 1.68% abnormalities. Human Papillomavirus testing detected 103 CIN2, 89 CIN3, and one AIS, compared with 24 CIN2 and 54 CIN3 detected by cytology (p < 0.0001). The age group between 25 and 29 years old screened by HPV testing had 2.4 to 3.0 times more positivity, 13.0% colposcopy referral, twice more than women aged 30 to 39 years old (7.7%; p < 0.0001), and detected 20 CIN3 and 3 early-stage cancer versus 9 CIN3 and no cancer by cytology screening (CIN3 OR= 2.10; 95%CI: 0.91 -5.25; p = 0.043). The PPV of colposcopy for CIN2+ ranged from 29.5 to 41.0% in the HPV testing program. Conclusion There was a significant increase in detections of cervix precancerous lesions in a short period of screening with HPV testing. In women < 30 years old, the HPV testing exhibited more positivity, high colposcopy referral rate, similar colposcopy PPV to older women, and more detection of HSIL and early-stage cervical cancer.

Resumo Objetivo Avaliar as taxas de lesões pré-cancerosas, encaminhamento para colposco pia e valor preditivo positivo (VPP) por faixas etárias de rastreamento populacional com teste DNA-HPV. Métodos O presente estudo de demonstração comparou 16.384 testes de HPV realizados nos primeiros 30 meses do programa com 19.992 mulheres testadas no rastreio citológico. Os programas foram comparados por taxa de encaminhamento de colposcopia e VPP para NIC2+ e NIC3+ por faixa etária. A análise estatística utilizou o teste de qui-quadrado e odds ratio (OR, na sigla em inglês) com intervalo de confiança (IC) de 95%. Resultados Os testes de HPV foram 3,26% positivos para HPV16-HPV18 e 9,92% positivos para 12 outros HPVs, com uma taxa de encaminhamento de colposcopia 3,7 vezes maior do que o programa de citologia, que teve 1,68% de anormalidades. O teste de HPV detectou 103 NIC2, 89 NIC3 e um AIS, em comparação com 24 NIC2 e 54 NIC3 detectados por citologia (p < 0,0001 ). O rastreio por teste de HPV no grupo etário 25 a 29 anos teve 2,4 a 3,0 vezes mais positividade, 13,0% de encaminhamento para colposcopia, 2 vezes mais que mulheres de 30 a 39 anos (7,7%; p < 0,0001 ), e detectou 20 NIC3 e 3 cânceres em estágio inicial versus nove NIC3 e nenhum câncer pelo rastreio citológico (NIC3 OR= 2,10; 96%CI: 0,91 -5,25; p = 0,043). O VPP da colposcopia para NIC2+ variou de 29,5 a 41,0% no programa de teste de HPV. Conclusão Houve um aumento significativo na detecção de lesões pré-cancerosas do colo do útero em um curto período de rastreamento com teste de HPV. Em mulheres < 30 anos, o teste de HPV exibiu mais positividade, alta taxa de encaminhamento para colposcopia com VPP semelhante a mulheres mais velhas, e mais detecção de HSIL e de câncer cervical em estágio inicial.

Tamización primaria con prueba ADN-VPH en mujeres menores de 30 años: evaluación de tecnología sanitaria / Primary HPV-DNA screening in women under 30 years of age: health technology assessment

Antecedentes A partir del 2014 en Colombia se incorporó la Tamización primaria con prueba de Virus del Papiloma Humano (VPH) desde los 30 hasta los 65 años, cuando la prueba es positiva se hace triage con citología para remisión a colposcopia. Actualmente se discute la conveniencia de iniciar la tamización con prueba de ADN de VPH a partir de los 25 años. De esta manera, el objetivo de esta evaluación de tecnologías sanitarias es analizar la evidencia disponible en torno a la seguridad, efectividad, costoefectividad, valores y preferencias, dilemas éticos y aspectos relacionados con la implementación para el contexto colombiano de la prueba ADN-VPH como estrategia de tamización cervical en mujeres menores de 30 años. Dominios a evaluar Eficacia clínica y seguridad 1. Tasa acumulada de neoplasia intraepitelial cervical (NIC) grado 2 o más avanzado luego de 2 rondas de tamización. 2. Tasas acumuladas de cáncer invasor de cérvix luego de 2 rondas de tamización. 3. Seguridad: remisión a colposcopia. Costo-efectividad Costo efectividad para Colombia. Otros dominios considerados Aspectos éticos asociados a la tamización cervical en mujeres menores de 30 años. Aspectos organizacionales y del individuo. Barreras y facilitadores relacionados con la implementación en el contexto colombiano de la tamización cervical en mujeres menores de 30 años. Métodos Evaluación de efectividad y seguridad clínicas Se realizó una búsqueda sistemática de la literatura en MEDLINE, Embase y CENTRAL de revisiones sistemáticas y ensayos clínicos. Se calificó el cuerpo de la evidencia con la aproximación GRADE. Posteriormente, se convocó a un grupo interdisciplinario a una mesa de trabajo en donde se presentó la evidencia recuperada, dando paso a la discusión y a la construcción de las conclusiones, siguiendo los lineamientos de un consenso formal acorde a la metodología RAND/UCLA. Estudio económico Se hizo una búsqueda sistemática de la literatura de estudios que hubieran evaluado el costo-efectividad para Colombia. Resultados De 7.659 referencias recuperadas se incluyeron 8 estudios. Resultados clínicos Se realizó un análisis integrativo de 5 ensayos clínicos aleatorizados que cumplieron con los citerios de inclusión. Cuando se compara frente a la citología, la tamización primaria con ADN-VPH en mujeres menores de 30 años, podría asociarse con una mayor frecuencia de detección de lesiones NIC2+ durante la primera ronda de cribado (RR: 1.57; IC: 1,20 a 2,04; certeza en la evidencia baja), con una menor incidencia de NIC2+ (RR:0,67; IC: 0,48 a 0,92; certeza en la evidencia baja) y se asocia con una menor frecuencia de carcinoma invasor al término del seguimiento (RR: 0,19; IC: 0,07 a 0,53; certeza en la evidencia alta). Resultados económicos Desde el punto de vista económico, la alternativa de ADN-VPH y triage con citología desde los 25 años quizás representa la alternativa más costo-efectiva para Colombia (razón costo-efectividad incremental $8.820.980 COP año 2013). Otras implicaciones Dos estudios sugieren que las barreras de implementación, atribuibles a circunstancias de intermediación, de orden público y de carácter geográfico, podrían ser solventadas por nuevas tecnologías o estrategias de cribado. Es importante considerar alternativas de forma de administración y de prestación de servicios para solventar algunas barreras de aceptabilidad y acceso. Todo programa de tamización cervical debe contemplar los principios éticos de no maleficencia, beneficencia, autonomía y equidad. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años. Conclusiones El uso de la prueba ADN-VPH como estrategia de tamización en mujeres menores de 30 años es una intervención probablemente efectiva y costoefectiva para Colombia. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años.

Background Primary screening with Human Papilloma Virus (HPV) testing was introduced in Colombia in 2014 for individuals between 30 and 65 years of age. When the result is positive, cytology triage is performed for colposcopy referral. The convenience of initiating HPV-DNA testing for screening at 25 years of age is currently a subject of discussion. Therefore, the objective of this health technology assessment (HTA) is to analyze the available evidence regarding safety, efficacy, cost-effectiveness, values and preferences, ethical dilemmas and considerations pertaining to the implementation of the HPV-DNA test as a cervical screening strategy in women under 30 years of age in the Colombian context. Domains to be assessed Clinical efficacy and safety 1. Cumulative rate of cervical intraepithelial neoplasia (CIN) grade 2 or high-er after 2 screening rounds. 2. Cumulative rates of invasive cancer of the uterine cervix after 2 screening rounds. 3. Safety: referral to colposcopy Cost-effectiveness Cost-effectiveness for Colombia. Other domains considered Ethical considerations associated with cervical screening in women under 30 years of age. Organizational and individual considerations. Barriers and facilitators pertaining to the implementation of cervical screening in women under 30 years of age in the Colombian context. Methods Clinical efficacy and safety assessment A systematic literature search of systematic reviews and clinical trials was conducted in MEDLINE, Embase and CENTRAL. The body of evidence was rated using the GRADE approach. An interdisciplinary team was then convened to create a working group to review the retrieved evidence. This led to the discussion and construction of the conclusions following the guidelines of a formal consensus in accordance with the RAND/UCLA methodology. Economic study Systematic literature research of studies that had assessed cost-effectiveness for Colombia. Results Out of the 7,659 references retrieved, 8 studies were included. Clinical outcomes An integrative analysis of 5 randomized clinical trials that met the inclusion critera was performed. Compared with cytology, primary HPV-DNA testing in women under 30 years of age could be associated with a lower frequency of CIN+2 lesions during the first screening round (RR: 1.57; CI: 1.20 to 2.04; low evidence certainty), and a lower incidence of CIN+2 (RR: 0.67; CI: 0.48 to 0.92; low evidence certainty). Moreover, it is associated with a lower frequency of invasive carcinoma at the end of follow-up (RR: 0.19; CI: 0.07 to 0.53; high evidence certainty). Economic results From the financial point of view, the use of HPVDNA testing plus cytology-based triage starting at 25 years of age is perhaps the most cost-effective option for Colombia (incremental cost-effectiveness ratio, COP 8,820,980 in 2013). Other implications Two studies suggest that barriers to implementation attributable to intermediation, public unrest and geographic considerations could be overcome with the use of new screening technologies or strategies. It is important to consider administration and service provision alternatives in order to overcome some acceptability and access barriers. Any cervical screening program must take into consideration ethical principles of nonmaleficence, beneficence, autonomy and equity. Future studies should focus on analyzing new screening techniques with emphasis on the population under 30 years of age. Conclusions The use of HPV-DNA testing as a screening strategy in women under 30 years of age is a potentially efficacious and cost-effective intervention for Colombia. Future studies should focus on analyzing new screening technologies, with emphasis on the population under 30 years of age.

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.

Rastreamento do câncer do colo do útero com teste de DNA-HPV: atualizações na recomendação / Cervical cancer screening with DNA-HPV testing: updates on the recommendation

Esta é uma atualização da recomendação de especialistas publicada em 2018 para o uso do teste de detecção do DNA-HPV de alto risco no rastreamento do câncer do colo do útero no Brasil, de acordo com as mudanças observadas nas diretrizes internacionais e atualizações do conhecimento. As recomendações mais relevantes e recentes foram revisadas. Questões referentes à prática clínica foram formuladas, e as respostas consideraram a perspectiva do sistema de saúde brasileiro, tanto público quanto privado. Essa 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. O objetivo é melhorar as estratégias de prevenção do câncer do colo do útero e reduzir o supertratamento e o uso incorreto dos testes de HPV.(AU)

Neoplasia intraepitelial escamosa cervical: abordagem por estimativas de risco / Cervical squamous intraepithelial neoplasia: risk estimation approach

As neoplasias intraepiteliais cervicais representam a fase pré-tumoral da neoplasia invasiva do colo uterino; são identificadas por citologia e testes de DNA-HPV e conduzidas por intervenções ambulatoriais. A perspectiva de estimativas de risco, para abordagem de tais lesões, constitui uma verdadeira mudança de paradigma, tendo em vista que as recomendações serão baseadas em riscos, não em resultados.(AU)

Cervical intraepithelial neoplasms represent the pre-tumor phase of invasive cervical cancer; identified by cytology, HPV-DNA testing and conducted by outpatient interventions. The perspective of risk estimates, to address such injuries, constitutes a true paradigm shift, considering that recomendations will be based on risks, not results.(AU)

Histerectomia radical após parto cesáreo por adenocarcinoma de colo uterino: relato de caso / Radical hysterectomy after c-section in cervical adenocarcinoma: a case report

Mundialmente, o câncer de colo uterino ocupa o quarto lugar das neoplasias em mulheres, porém, nos países em desenvolvimento, as taxas de incidência superam de forma impactante os casos de países desenvolvidos. Apesar de ser um evento incomum durante a gestação, é cada vez mais observado, o que talvez possa ser atribuído às gestações programadas em idades mais avançadas. O caso descrito refere-se a uma paciente de 32 anos de idade, diagnosticada no terceiro trimestre da gestação com adenocarcinoma de origem endocervical com estadiamento anatomopatológico final (FIGO 2018) 1B2. Ela foi submetida à abordagem cirúrgica como tratamento inicial. Foi adotada como conduta a resolução da gestação, com boa vitalidade fetal, ao final da 34ª semana, após corticoterapia para maturação pulmonar fetal. Foi realizado parto cesariano seguido de histerectomia radical tipo C1 na classificação de Querleu e Morrow associado a linfadenectomia pélvica, no mesmo ato operatório.(AU)

Worldwide, cervical cancer ranks fourth in female cancers, but when assessing data from developing countries, incidence rates are significantly higher than in developed countries. Although it is an uncommon event during pregnancy, it is increasingly observed, which may perhaps be justified due to pregnancies postponed at older ages. The case described relates to a 32-year-old woman diagnosed in the third trimester of pregnancy with endocervical adenocarcinoma, whose final anatomopathological staging (FIGO 2018) was IB2. The same was submitted to the surgical approach as an initial treatment. It was adopted as a conduct, the resolution of pregnancy, with good fetal viability, at the end of the 34th week, after corticosteroid therapy for fetal lung maturation. The patient underwent cesarean section followed by radical type C1 hysterectomy in the classification of Querleu and Morrow associated with pelvic lymphadenectomy in the same surgery.(AU)

Riesgo de desarrollar LIE-AG en pacientes con tamizaje inicial positivo para VPH y citología cervicovaginal negativa en seguimiento hasta 10 años: revisión sistemática y metaanálisis / Risk of developing H-SIL in patients with initial positive screening for HPV and negative cervicovaginal cytology in follow-up up to 10 years: systematic review and meta-analysis

Resumen Introducción: El cáncer de cérvix es el segundo en frecuencia y el tercero en mortalidad; la infección por el virus del papiloma humano (VPH) está asociada al riesgo de cáncer; sin embargo, no se conoce el riesgo acumulado a 1, 2, 3, 5 y 10 años. Objetivo: Determinar el riesgo de las pacientes VPH positivo con evaluación inicial citológica negativa para desarrollar lesión intraepitelial de alto grado a lo largo del tiempo. Método: Se realizó una revisión sistemática de artículos en inglés y español de los últimos 20 años, usando las bases de datos PubMed, Cochrane, LILACS, ProQuest y Embase. Se incluyeron ensayos clínicos aleatorizados en los que se determinaba el estado VPH y se realizaba seguimiento con citología cervicovaginal a 1, 2, 3, 5 y 10 años en mujeres de 20-64 años. Resultados: Se incluyeron siete ensayos clínicos aleatorizados, con un total de 98.521 mujeres, de ellas 8820 VPH positivo y 89.701 VPH negativo al ingreso, seguidas hasta por 10 años con citología cervicovaginal, encontrando que la infección por VPH es un factor de riesgo para desarrollar lesiones intraepiteliales de alto grado a 2, 5 y 10 años, con un riesgo relativo de 110.94 (79.41-154.97), 83.65 (55.22-126.73) y 29.71 (5.72-154.33), respectivamente. Conclusiones: La infección por VPH es un factor de riesgo importante para el desarrollo de lesiones intraepiteliales de alto grado a 2, 5 y 10 años.

Abstract Introduction: Cervical cancer is the second in frequency and the third in mortality, infection by the human papillomavirus (HPV) is associated with the risk of increased cancer; however, the cumulative risk of 1, 2, 3, 5 and 10 years is not known. Objective: To determine the risk of HPV-positive patients with negative initial cytological evaluation for developing high-grade intraepithelial lesion over time. Method: A systematic review of articles in English and Spanish in the last 20 years was carried out, using the PubMed, Cochrane, LILACS, ProQuest and Embase databases. Randomized clinical trials were included in which HPV was performed and subsequent follow-up with cervicovaginal cytology at 1, 2, 3, 5 and 10 years in women aged 20-64 years. Results: Seven randomized clinical trials were included, a total of 98,521 women, 8820 with positive HPV and 89701 negative on admission and followed up for up to 10 years with cervicovaginal cytology. Finding that HPV infection is a risk factor for developing high-grade intraepithelial lesion at 2, 5 and 10 years with a relative risk of 110.94 (79.41-154.97), 83.65 (55.22- 126.73) and 29.71 (5.72-154.33), respectively. Conclusions: HPV infection is an important risk factor for the development of high-grade intraepithelial lesion at 2, 5 and 10 years.

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.

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

Human papillomavirus (HPV) DNA detection in uterine cervix cancer after radiation indicating recurrence: a systematic review and meta-analysis / 부인종양

OBJECTIVE: The causal association of human papillomavirus (HPV) in uterine cervical cancer was well established and this oncogenic virus was reported to be a biomarker for overall recurrence and central pelvic recurrence. The objective of the present systematic review and meta-analysis was to assess the role of HPV DNA testing in early detection of recurrence among cervical cancer survivors after radiotherapy.METHODS: We performed a systematic review and meta-analysis by means of searching electronic databases for published articles between January 1984 and June 2018, on the basis of standard systematic review guidelines prescribed by major agencies namely Cochrane Collaboration (https://www.cochrane.org) and Campbell Collaboration (https://www.campbellcollaboration.org). The meta-analysis component was further modified appropriately for the synthesis of sensitivity and specificity results.RESULTS: A total of 1,055 cervical cancer cases who had received pelvic radiation with or without chemotherapy from ten cohort studies were evaluated. The overall pooled sensitivity and specificity of HPV DNA testing was 0.84 (95% confidence interval [CI]= 0.66–0.94) and 0.35 (95% CI=0.20–0.54) respectively. The positive likelihood ratio was 1.3 (95% CI=1.0–1.7) and the negative likelihood ratio was 0.45 (95% CI=0.18–1.10) with an estimated diagnostic odds ratio of 3 (95% CI=1–9).CONCLUSION: The screening for HPV DNA testing during follow-up facilitates early detection of recurrence after radiotherapy.

El impacto de la prueba de VPH en los programas de tamizaje en América Latina: el caso de Argentina / The impact of the HPV test in screening programs in Latin America: The case of Argentina

Resumen: Objetivo: Evaluar el impacto de la prueba de VPH (prueba de VPH) en los problemas que históricamente afectaron al tamizaje de cáncer cervical en América Latina, tomando como caso al Proyecto Demostración para la Introducción de la prueba de VPH en Jujuy (PDJ), Argentina. Material y métodos: Se sintetizó la evidencia sobre los problemas del tamizaje cervical en la región. Se analizó el impacto en los problemas a partir de la introducción de la prueba de VPH. El impacto se clasificó en directo/indirecto y positivo/negativo. Resultados: El impacto directo-positivo se dio en los problemas de adherencia a la edad/frecuencia de tamizaje, laboratorios de citología, baja/moderada sensibilidad de la citología y baja cobertura. El impacto directo-negativo se vinculó con el triaje de autotoma y el envío/etiquetado de muestras. El impacto indirecto-positivo se relacionó con la reorganización programática realizada para introducir la prueba de VPH. Conclusiones: La prueba de VPH representa una ventana de oportunidad para el mejoramiento del tamizaje pero no resuelve los problemas programáticos.

Abstract: Objective: To assess the impact of HPV testing on longstanding problems faced by screening programs in Latin America, using the case of the Jujuy Demonstration Project (JDP) in Argentina. Materials and methods: The study measured the level of impact produced by the introduction of HPV-testing on problems faced by cytology programs by analyzing modifications on specific problems produced during the JDP. Impact was classified as direct/indirect, and positive/ negative. Results: Direct/positive impact was found in issues concerning age and screening frequency, cytology laboratories and screening sensitivity, and low coverage. Direct/negative impact was mainly related to the adherence to triage cytology by HPV+ women with self-collected-tests, and the delivery and labelling of samples. Indirect impact of HPV-Test was mostly positive, and related to the programmatic reorganization which was facilitated by the introduction of HPV testing. Conclusions: HPV testing provides an opportunity window for improving primary screening, but does not solve programmatic problems.

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.

Risk of cervical dysplasia among human papillomavirus-infected women in Korea: a multicenter prospective study / 부인종양

OBJECTIVE: Human papillomavirus (HPV) infection is the most important risk factor for cervical cancer, which progresses from precursor lesions with no symptom if left untreated. We compared the risk of cervical dysplasia among HPV-positive Korean women based on HPV types and infection patterns. METHODS: We observed participants of a 5-year multicenter prospective cohort study, comprising HPV-positive women with either atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion of the cervix at their enrollment. Follow-ups, comprising cytology and HPV DNA testing results, were included in the final analysis. Incidence was calculated for each infection pattern (persistent infection, incidental infection, and clearance). To investigate cervical dysplasia risk, we used Cox proportional hazard models adjusted for variables that were significantly different among infection patterns. From April 2010 to September 2017, 71 of 1,027 subjects developed cervical dysplasia more severe than high-grade squamous intraepithelial lesion of the cervix. RESULTS: Of these 71 subjects, persistent infection, incidental infection, and clearance were noted in 30, 39, and 2 individuals, respectively. Based on changes in DNA results during follow-up, cumulative incidence was 27.2%, 10.4%, and 0.5% for persistent infection, incidental infection, and clearance, respectively. Compared to clearance, the adjusted hazard ratios for cervical dysplasia were 51.6 and 24.1 for persistent and incidental infections, respectively (p < 0.001). CONCLUSION: Individuals persistently infected with the same HPV types during the follow-up period had the highest risk of severe cervical dysplasia. Hence, it is necessary to monitor HPV types and infection patterns to prevent severe cervical precancerous lesions.

Adopción e implementación del ofrecimiento de la autotoma VPH por agentes sanitarios en Jujuy, Argentina / Adoption and implementation of HPV self-collection sampling by CHWs in Jujuy, Argentina

Resumen: Objetivo: Evaluar la adopción e implementación en escala de la estrategia orientada a ofrecer puerta a puerta la autotoma de la prueba del virus del papiloma humano (AT-VPH), por parte de agentes sanitarios (AS), en Jujuy, Argentina. Material y métodos: Se aplicó una encuesta autoadministrada a 478 AS. Las dimensiones de adopción e implementación fueron evaluadas con el modelo RE-AIM. Resultados: Adopción: 81.8% de los AS ofreció la AT-VPH y 86.4% expresó gratificación con la estrategia. Implementación: los problemas encontrados fueron la demora en la entrega de tubos (61.3%) y resultados (70.0%); falta de recursos humanos (28.3%), y dificultades al obtener turnos para realizar el triage (26.1%). El principal obstáculo fue la sobrecarga de trabajo (50.2%), mientras que la capacitación (38.0%) y el listado de mujeres a contactar (28.7%) fueron los elementos facilitadores. Conclusiones: La adopción de la AT-VPH fue alta entre los AS. Deben reforzarse las estrategias programáticas para motivar a los AS y reducir su carga de trabajo al implementar la AT-VPH.

Abstract: Objective: To evaluate adoption and implementation of scaling up of HPV self-collection (SC) strategy offered door-to-door by Community Health Workers (CHWs) in Jujuy, Argentina. Materials and methods: A self-administered questionnaire was applied to 478 CHWs. RE-AIM model was used to evaluate adoption and implementation dimensions. Results: Adoption: 81.8% offered SC and 86.4% were satisfied with the strategy. Implementation: main problems were delays in the delivery of tubes (61.3%) and results (70.0%), lack of human resources (28.3%) and difficulties in obtaining an appointment for triage (26.1%). The main obstacle was the excessive workload of CHWs (50.2%). Training (38.0%) and the list of women to be offered the test (28.7%) were identified as facilitators. Conclusions: The adoption of SC strategy was high among CHWs. Program strategies should be strengthened to motivate and reduce the excessive workload of CHWs when implementing SC strategy.

Nuevas estrategias de prevención y control de cáncer de cuello uterino en Chile / New strategies for the prevention and control of cervical cancer in Chile

Resumen: Objetivos: Discutir el cáncer cervicouterino (CC), el virus del papiloma humano (VPH), el programa de control del CC y proponer alternativas para Chile. Material y métodos: Se analiza el programa nacional del CC 1966-2015 y la guía clínica 2015-2020, la prevalencia de VPH en mujeres y en casos de CC; la infección y serología de VPH; la autotoma; la precisión y rentabilidad del tamizaje con VPH contra el Papanicolaou y las opciones de triaje en VPH AR positivas. Resultados: En Chile mueren 600 mujeres (principalmente de bajos recursos) al año por CC. La cobertura del Papanicolaou es < 70%, sensibilidad muy inferior al test de VPH, por lo que el cambio es rentable. Desde 2015 se vacuna contra VPH a niñas menores de 13 años. Conclusiones: Las condiciones técnicas y económicas existen en Chile para lograr una mejoría sustancial del CC: se sugiere el reemplazo del Papanicolaou por el examen de VPH; tamizaje cada cinco años con opción de autotoma; triaje con base en la tipificación de VPH 16/18 o Papanicolaou.

Abstract: Objective: To discuss cervical cancer (CC), Human Papilloma Virus (HPV), CC control program and propose alternatives for Chile. Materials and methods: We analyzed the national program of CC 1966-2015 and the clinical CC guideline 2015-2020; HPV prevalence in women and in cases of CC; HPV infection and serology; the self-vaginal sample; the accuracy and cost-effectiveness of screening with HPV versus Papanicolaou, and triage options among HPV-AR positives. Results: 600 women die of CC each year in Chile, mainly from low resources. Papanicolaou coverage is <70%; Papanicolaou sensitivity is much lower than HPV test. Change from Papanicolaou to HPV test is cost-effective. Since 2015, girls under 13 have been vaccinated against HPV. Conclusions: There are the technical and economic conditions for a substantial improvement of CC in Chile: replacement of the Papanicolaou by HPV; screening every five years, with the option of self-sampling, and triage based on HPV 16/18 or Papanicolaou typing.

Use of HPV testing in cervical cancer screening services in Mexico, 2008-2018: a nationwide database study / Uso de la prueba de VPH para la detección de cáncer cervical en México, 2008-2018: estudio de una base de datos nacional

Abstract: Objective: To describe the methods of a study aimed at evaluating high risk-HPV (hrHPV)-based screening and cervical cytology as triage compared to conventional cervical cytology as primary screening in the detection of grade 2+ cervical intraepithelial neoplasia in the National Cancer Screening Program (NCSP) of Mexico. Materials and methods: We will use information originated from the Womens Cancer Information System of Mexico regarding cervical cancer from 2008 to 2018. The database includes cytology results, diagnostic confirmation by histopathology and/or treatment colposcopy. We will then carry out statistical analyses on approximately 15 million hrHPV. Results: We will evaluate the overall performance of hrHPV-based screening as part of the NCSP and compare hrHPV-based to cytology-based screening under real-life conditions. To guarantee an unbiased comparison between hrHPV with cytology triage and conventional cytology we will use propensity score matching. Conclusion: Decision makers may use our results to identify areas of opportunity for improvement in NCSP processes.

Resumen: Objetivo: Describir los métodos de un estudio que busca comparar el beneficio de la introducción de la prueba de VPH de alto riesgo como prueba primaria frente a la citología convencional para la detección de la neoplasia intraepitelial cervical grado 2 o mayor, dentro del Programa de Prevención y Control del Cáncer de la Mujer, para el periodo de 2008 a 2018. Material y métodos: Se utilizarán los registros del Sistema de Información de Cáncer de la Mujer, se realizarán los análisis estadísticos con aproximadamente 15 millones de resultados de VPH-alto riesgo, además se utilizarán los resultados de citología, colposcopia, histología y los casos referenciados al centro oncológico para tratamiento. Para comparar ambos grupos usaremos "propensity score matching". Resultados: Se evaluará el desempeño general de la prueba de VPH-alto riesgo, en condiciones reales dentro del Programa Nacional de Prevención y Control de la Mujer y su tendencia en el tiempo. Conclusiones: Los resultados de estudio ayudarán a los tomadores de decisiones a identificar áreas de oportunidad para mejorar el programa en México.