Cervical Cancer Screening with DNA-HPV Testing and Precancerous Lesions Detection: A Brazilian Population-based Demonstration Study.

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.

OBJETIVO: Avaliar as taxas de lesões pré-cancerosas, encaminhamento para colposcopia 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: 0,91­5,25; 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.

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.

Organization of cervical cancer screening with DNA-HPV testing impact on early-stage cancer detection: a population-based demonstration study in a Brazilian city.

Background: Cervical cancer is a preventable disease, and the Brazilian screening is opportunistic and has low impact. The current study evaluated an initiative to organize screening using DNA-HPV testing as a replacement for cytology. Methods: This demonstration study examined information from 16 384 DNA-HPV tests for screening in women aged 25-64 years from Indaiatuba city between October 2017-March 2020. The comparison was 20 284 women screened using cytology between October 2014-March 2017. The flowchart indicates the repetition of a negative test in five years. HPV16- and/or HPV18-positive tests and the 12 pooled high-risk HPV-positive tests with abnormal liquid-based cytology were referred for colposcopy. If cytology was negative, the HPV test was repeated in 12 months. The analyses evaluated coverage, age-group compliance, and cancer detected. Findings: After 30 months, the coverage projection was greater than 80%. The age compliance for the HPV test was 99.25%, compared to 78.0% in the cytology program. The HPV test program showed 86.8% negative tests and 6.3% colposcopy referrals, with 78% colposcopies performed. The HPV testing program detected 21 women with cervical cancer with a mean age of 39.6 years, and 67% of cancers were early-stage compared to 12 cervical cancer cases detected by cytological screening (p=0.0284) with a mean age of 49.3 years (p=0.0158), and one case of early-stage (p=0.0014). Interpretation: Organizing cervical cancer screening using DNA-HPV testing demonstrated high coverage and age compliance in a real-life scenario, and it had an immediate impact on cervical cancer detection at an early-stage. Funding: University of Campinas, Indaiatuba City, and Roche Diagnostics.

Cervical cancer in women under 25 years of age and outside the screening age: Diagnosis profile and long-term outcomes.

OBJECTIVE: To evaluate the pattern of cervical cancer (CC) diagnosis and outcomes in women under 25. METHODS: Thirty-two women younger than 25 years of age treated between 2001 and 2016 were studied and the year, symptom or cytology before diagnosis, time since sexual debut, age group, histology, and stage were considered. Data were compared with older age groups, and survival analysis was performed using a subset of them. RESULTS: Thirty-two CC diagnoses (1.5% of all cases) exhibited a positive linear trend (P = 0.075). Driven by cytology, 18 were asymptomatic and 14 were symptomatic (with vaginal bleeding in 11). The mean time since sexual debut was 6.9 years. Advanced stage (44% vs 29%) and adenosquamous histology (12.5% vs 1.7%-5.0%) were higher in younger women. Five-year overall survival rate was 76%, better for squamous cell carcinoma (SCC) (86% vs 43% for other histologies; P = 0.018). There were seven deaths, all within 15 months of diagnosis. Age groups of less than 25 years (53%) and 25-29 years (48.5%) had similar proportions of Stage IA1. CONCLUSION: The rate of CC-diagnosed women under 25 years was 1.5% of all cases, exhibiting more advanced stage and non-SCC histology. For asymptomatic women, cytology allowed the diagnosis at an early stage. Being symptomatic and non-SCC was associated with a higher proportion of advanced stages and poor survival.

Cervical cancer screening program based on primary DNA-HPV testing in a Brazilian city: a cost-effectiveness study protocol.

BACKGROUND: The causal relationship between high-risk (hr) HPV infection and precancerous lesions or cervical cancer has led to the development of strategies to increase screening performance and prevent this cancer. The increased sensitivity of DNA-HPV testing compared to cervical cytology favors DNA-HPV testing as a primary screening test. Cervical cancer screening in Brazil is opportunistic, and this cancer remains a considerable health problem with a high proportion of diagnoses in advanced stages. This paper aims to describe the design and implementation of the Cervical Cancer Screening Program with primary DNA-HPV testing (CCSP-HPV) planned for Indaiatuba City (SP), Brazil; the strategies to achieve higher population coverage; and a study protocol for cost-effectiveness analyses. METHODS: The CCSP-HPV was designed based on successful guidelines that replaced cervical cytology-based screening by the DNA-HPV test performed at 5-year intervals. The screening will be performed for the female population aged 25-64 years cared for by the public health system and aim to reach 80% coverage after completing the first round. The chosen DNA-HPV test detects 14 hr-HPV types and genotypes HPV-16 and 18. All women with a negative test will be reassessed after five years. Women showing a positive test for HPV-16 and/or 18 will be referred for colposcopy. Those showing the other 12 hr-HPV types will be tested by cytology, and if any abnormality is detected, they will also be referred for colposcopy. The histopathologic evaluation will be reviewed by a pathologist panel and aided by p16 immunohistochemistry. A cost-effectiveness analysis will be performed by a Markov model comparing the cost of the new program and the screening performed by conventional cytology five years prior (2011-2016). DISCUSSION: The new screening program is considered a breakthrough for public health regarding cervical cancer, which is the third leading cause of cancer death among Brazilian women. Achieving at least 80% coverage will have the possibility to change this scenario. The proposed program will provide a modern cervical cancer screening method for women, and information about cost-effectiveness will help other similar places support the decision of implementing cervical cancer screening using the DNA-HPV test.

Estresse e o trabalho / Stress and work

Os profissionais da área de saúde , principalmente os que atuam no ambiente ocupacional, estäo engajados nas mudanças que promovam o bem-estar dos trabalhadores, preocupando-se com os determinantes saúde-doença, e novas formas de produçäo, de organizar, e métodos inovadores para gerenciar e gerir trabalho, pois a combinaçäo de inovaçöes tecnológicas, com a intensificaçäo do trabalho, com ritmos acelerados, responsabilidades e complexidade das tarefas, vêm repercutindo em manifestaçöes, como envelhecimento prematuro, doenças cardiovasculares, outras doenças crônico-degenerativas, distúrbios osteomusculares relacionados ao trabalho (DORT), e conjunto de sintomas na esfera psíquica, como a Síndrome da Fadiga Crônica, Síndrome Burn out, outros distúrbios inespecíficos e poucos conhecidos, e morte súbitapor excesso de trabalho