The value of the endocervical margin status in LEEP: analysis of 610 cases.

PURPOSE: To describe the results of 610 patients who underwent LEEP and evaluate factors related to a negative margin. METHODS: A retrospective study of patients treated by LEEP at a colposcopy referral service in Campinas, Brazil, 2017-2019. Patients were referred to treat high-grade squamous intraepithelial lesion or adenocarcinoma in situ suspected by cytology and colposcopy (screen-and-treat) or by biopsy. Descriptive analysis was performed by frequencies as a function of the status of the margins (negative or positive). Factors associated with margin status were assessed by regression. RESULTS: The endocervical, ectocervical or both margins were negative in 82.4%, 75.7% and 65.9%, respectively. Age, sexual debut, parity, menopause status, smoking and hormonal contraception showed no difference in the proportion of negative margins. Both margins were negative in 66.1% of patients with transformation zone type(TZ) 1, 73.1% of TZ 2, and 54.7% of TZ 3 (p = 0.015). The endocervical negative margin was obtained in 78.0% of patients submitted to excision I (loop 10 mm) and 82.5% to excision II (loop 15 mm) (p = 0.016). Having the sexual debut at 18 years or older or being submitted to an excision type II doubled the chance of negative endocervical margin (1.98;1.04-3.77 and 1.95; 1.18-3.21, respectively). CONCLUSION: The proportion of negative endocervical margin was 78% in excision I and 86% in excision II. Sexual onset and excision type II increased the chance of obtaining a negative endocervical margin.

Endocervical Margins Status in Excision for Preventing Cervical Cancer According to the Transformation Zone Type.

OBJECTIVE: The aim of this study is to assess the outcomes of 610 excision types I and II in a referral facility as a function of transformation zone (TZ) types. METHODS: This is a retrospective cohort study of women with cervical precursor lesions who underwent loop electrocautery excision procedure from 2017 to 2019 at the University of Campinas. The primary outcome was endocervical margin status, negative or positive. Other variables were excision type (I/II), TZ (1/2/3), age, menopausal status, hormonal contraceptives, smoking, and sexual debut. Tests used were chi-square or Fisher exact, Mann-Whitney, and simple and multiple logistic regression. RESULTS: The most frequent was TZ 1 (62.5%). Excision II was the most frequent: 54.1% in TZ 1, 67.2% in TZ 2, and 82.1% in TZ 3. A negative margin was observed in TZ 1, 76.0% when excision I and 86.4% when excision II ( p = .009); TZ 2, 86.4% when excision I and 88.9% when excision II ( p = .672); and TZ 3, 76.5% when excision I and 78.9% when excision II ( p = .672). Multivariate analysis revealed in TZ 1 a 2.12 (1.23-3.65) higher risk of obtaining a negative margin in excision type II. In TZ 2 and 3, none of the variables predicted the chance of a negative margin. CONCLUSIONS: The endocervical margin was negative in 3 in every 4 women who underwent loop electrocautery excision procedure, regardless of excision type. Age, menopausal status, smoking, and hormonal contraception did not predict margin status.

Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: A randomized controlled trial.

OBJECTIVE: The present analysis determined the disease free survival (DFS) and overall survival (OS) at up to 14 years of follow-up in women who participated in our previous phase 3 randomized controlled clinical trial, in which women with stage IIIB squamous cervical cancer received either cisplatin plus RT or RT alone for treatment. The first study showed that the addition of cisplatin to RT offered a significant benefit in DFS, but not in OS. METHODS: The present analysis examined DFS and OS in 146 women from the original cohort (72 patients in the CRT arm and 74 patients in the RT-only arm) with follow-up of up to 14 years. RESULTS: Longer term follow-up showed that treatment with CRT offers a significant benefit in DFS and OS compared with treatment with RT only. Patients who received RT alone had significantly worse OS (HR, 1.88; 95% CI, 1.09-3.24) and DFS (HR, 1.82; 95% CI, 1.07-3.08) compared with patients who received CRT. The multivariate analyses also showed that the patients with baseline Karnofsky performance status (KPS) <90% showed significantly worse OS (HR, 3.11; 95% CI, 1.78-5.43), as did those with hemoglobin <10 mg/dL (HR, 4.32; 95% CI, 2.23-8.36). Patients with baseline KPS < 90% showed significantly worse DFS (HR, 2.83; 95% CI, 1.60-5.01), as did those with hemoglobin <10 mg/dL (HR, 4.16; 95% CI, 2.17-7.95). CONCLUSIONS: For stage IIIB cervical cancer, treatment with CRT offers a significant benefit in DFS and OS compared with treatment with RT only.

Is Diagnostic Hysteroscopy Safe for the Investigation of Type II Endometrial Cancer? A Retrospective Cohort Analysis.

STUDY OBJECTIVE: Although hysteroscopy (HSC) can be used for assessing the uterine cavity in women with suspected endometrial cancer (EC), it remains controversial as a procedure because it can potentially enhance the metastatic spread of cancer cells. Moreover, it is important to assess this hypothesis for type II EC, a more aggressive phenotype that usually presents with endometrial atrophy and has worse prognosis. Thus, we aimed to assess the prevalence of positive peritoneal cytology result in women with type II EC who underwent HSC as a diagnostic tool and to determine the factors associated with patient relapse/survival. DESIGN: Retrospective cohort analysis (2002-2017). SETTING: Tertiary, academic hospital. PATIENTS: One hundred twenty-seven women with type II EC. INTERVENTIONS: Diagnostic HSC (HSC) (n = 43) or dilation/curettage (D&C) (n = 84). MEASUREMENTS AND MAIN RESULTS: Primary end point was the frequency of positive peritoneal cytology result. Survival curves were projected using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis with hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to assess the factors related with the disease-free survival (DFS) and the disease-specific survival (DSS). Advanced cancer stage and greater vascular invasion appeared more frequently in the D&C group (p = .008 and p = .04, respectively). Positive peritoneal cytology result was present in 2 of 43 (4.6%) women following HSC and in 9 of 84 (10.7%) following D&C (p = .22). DFS and DSS curves did not statistically differ between the groups. Multivariate analysis for DFS revealed that advanced cancer stage (III and IV) (HR = 4.67; 95% CI, 2.34-9.34; p <.001) and advanced age (HR = 1.08; 95% CI, 1.04-1.13]; p <.001) were the factors associated with relapse. For DSS, advanced age (HR = 1.08; 95% CI, 1.05-1.12; p <.001), cancer stage III/IV (HR = 3.95; 95% CI, 2.18-7.15; p <.001), and vascular invasion (HR = 2.47; 95% CI, 1.34-4.54; p = .004) increased the risk of mortality. CONCLUSION: Diagnostic HSC did not increase the rate of positive peritoneal cytology result at the time of surgical staging in this cohort of women with type II EC and is probably as safe as D&C.

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.

Estimating the public health impact of a national guideline on cervical cancer screening: an audit study of a program in Campinas, Brazil.

BACKGROUND: A Brazilian guideline on cervical cancer screening was released in 2011. The objective was to verify changes in screening indicators around this period. METHODS: An audit study which sample was all screening tests performed by the public health system of Campinas city from 2010 to 2016. Variables were absolute tests numbers, excess tests, intervals and results, by age. For trend analysis was used Cochran-Armitage × 2 and linear regression. RESULTS: Were carried out 62,925 tests in 2010 and 43,523 tests in 2016, a tendency at a reduction (P = 0.001). Excess tests were higher than 50% over the years, with a tendency at a reduction (P < 0.001). Tests performed on women under 25 ranged from 20.2 to 15.4% in the period (P < 0.001), while in the 25-64 years age-group, it ranged from 75.1 to 80.2% (P < 0.001). In 2010 the most frequent interval was annual (47.5%) and in 2016 biennial (34.7%). There was a tendency at a reduction in the proportion of tests performed at the first time and those with an annual interval (P < 0.001), and also a tendency at an increase in tests with intervals equal to or greater than biannual (P < 0.001). We observed a tendency at a reduction in LSIL and HSIL-CIN2 results (P = 0.04 and P = 0.001, respectively), and a tendency at an increase in HSIL-CIN3 result (P = 0.02). CONCLUSION: The proportion of cervical cancer screening tests performed out of the recommendation showed a significant reduction in the period. This indicates a tendency to align cervical cancer screening in Campinas with the standards recommended.

Analysis of Conservative Surgical Treatment and Prognosis of Microinvasive Squamous Cell Carcinoma of the Cervix Stage IA1: Results of Follow-Up to 20 Years.

OBJECTIVE: The aim of this study was to evaluate the prognosis and recurrence of microinvasive squamous cervical (MIC) cancer stage IA1 in women treated conservatively or by hysterectomy, and followed-up to 20 years. METHODS: It was studied in a cohort of 139 women with MIC, 41 definitively managed by conization and 98 by hysterectomy from January 1994 to December 2003 and followed-up until 2013. The definitive treatment, age, conization technique (loop electrosurgical excision procedure or cold knife conization), cone margin, residual disease in hysterectomy specimen, and the association with recurrence (intraepithelial cervical neoplasia grade 3/intraepithelial vaginal neoplasia grade 3 or worse, and microinvasive or worse) were analyzed. RESULTS: There were 2.5 times more conservative treatment in younger women than older (>40 years), and high proportion of residual disease in hysterectomy specimens (67% of intraepithelial cervical neoplasia grade 3 or worse), more common if positive cone margin (74% vs 35%, P < 0.002). There were 2.3% (3/133) recurrences detected as microinvasive or worse, and 6% (8/133) recurrences detected as intraepithelial cervical neoplasia grade 3/intraepithelial vaginal neoplasia grade 3 or worse: 7.3% (3/41) in the conization group and 5.4% (5/92) in the hysterectomy group (P = 0.701). Almost all recurrences (88%, 7/8) were diagnosed until 36 months after treatment, and they were not associated with conization technique. There were no differences in risk of recurrence and overall disease-free survival time related to type of treatment. CONCLUSIONS: This study demonstrates the good prognosis of MIC, regardless the treatment. When fertility is not a concern, hysterectomy should be considered as definitive treatment to avoid the risk of residual disease. Regular follow-up for a long period should be maintained.

Microinvasive adenocarcinoma of the cervix in a young woman vaccinated against human papillomavirus: the screening must be continued.

OBJECTIVE: This report describes a case that illustrates the limitations of the vaccination screening process for human papillomavirus (HPV) infection. CASE: We report an unexpected microinvasive adenocarcinoma of the cervix arising in a young woman vaccinated against HPV as part of a clinical trial 6 years previously and followed up annually by cytology. In January 2012, at age 23 years, the patient received a cytological result of atypical squamous cells, cannot exclude high-grade cervical squamous intraepithelial lesion, and colposcopy showed slight abnormalities. Biopsy revealed an adenocarcinoma in situ. Conization of the cervix was performed, and the diagnosis was microinvasive adenocarcinoma. Polymerase chain reaction and immunohistochemical study of conization material showed positivity for HPV-18 L1, p16, and Ki-67. Retrospective analysis of the clinical trial information revealed that 7 HPV tests had been performed, and all were positive for HPV-18, including the sample collected before the first vaccination. CONCLUSIONS: HPV-18 was present in the cervix before vaccination. Persistent detection of HPV-18 should be considered an important factor in treatment planning. This case demonstrates the need to vaccinate women before their first sexual contact and highlights the need for keeping adequate screening even in vaccinated individuals.

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.

Association of Fibrinolytic Potential and Risk of Mortality in Cancer Patients.

Cancer is a leading cause of death, and the fibrinolytic system shows cooperative effects that facilitate the growth of tumors and the appearance of metastases. This prospective study aimed to evaluate the fibrinolytic potential in cancer patients and its association with mortality outcomes using the fluorometric method of simultaneous thrombin and plasmin generation. The study included 323 cancer patients and 148 healthy individuals. During the 12-month follow-up, 68 patients died. Compared to the control group, cancer patients showed alterations in thrombin production consistent with a hypercoagulability profile, and an increase in plasmin generation. Mortality risk was associated with two parameters of thrombin in both univariate and multivariable analysis: maximum amplitude (Wald 11.78, p < 0.001) and area under the curve (Wald 8.0, p < 0.005), while such associations were not observed for plasmin. In conclusion, this was the first study able to demonstrate the simultaneous evaluation of thrombin and plasmin generation in newly diagnosed untreated cancer patients. Patients with cancer have been observed to exhibit a hypercoagulable profile. During the study, two parameters linked to thrombin generation, MA and AUC, were identified and found to have a potential association with mortality risk. However, no associations were found with parameters related to plasmin generation.

[Association between sanitation services coverage and epidemiological indicators in Latin America: a study with secondary data]. / Associação entre cobertura por serviços de saneamento e indicadores epidemiológicos nos países da América Latina: estudo com dados secundários.

OBJECTIVE: To study the association between water and sanitation coverage and epidemiological indicators in Latin America, using secondary data from the Pan American Health Organization (PAHO) for the period of 2005 to 2010. METHODS: An ecological study was carried out including data from 21 Latin American countries, with a total estimated population of 596 million. The following variables were analyzed: infant mortality in children under 1 year in 2008, mortality in children under 5 years in 2008, and mortality from acute diarrheal diseases in children under 5 years in 2008. These indicators were analyzed by means of the "one-on-one" correlation with risk factors in five categories (demographic, socioeconomic, child health, public spending on health care, health care, and sanitation coverage). RESULTS: The average values for the region were 18.2 deaths per 1 000 live births in children under 1 year of age, 23.5 deaths per 1 000 live births for children under 5 years, and 5.8% mortality for acute diarrheal diseases in children under 5 years. Higher water and sanitation coverage was linked with lower mortality in children under 1 and under 5 years of age. Higher mortality from acute diarrheal diseases in children under 5 years was associated with higher annual population growth. CONCLUSIONS: The improvement of public health in Latin America depends on the expansion of access to public water and sanitation systems.

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.

Maternal Deaths from COVID-19 in Brazil: Increase during the Second Wave of the Pandemic.

OBJECTIVE: To compare death rates by COVID-19 between pregnant or postpartum and nonpregnant women during the first and second waves of the Brazilian pandemic. METHODS: In the present population-based evaluation data from the Sistema de Informação da Vigilância Epidemiológica da Gripe (SIVEP-Gripe, in the Portuguese acronym), we included women with c (ARDS) by COVID-19: 47,768 in 2020 (4,853 obstetric versus 42,915 nonobstetric) and 66,689 in 2021 (5,208 obstetric versus 61,481 nonobstetric) and estimated the frequency of in-hospital death. RESULTS: We identified 377 maternal deaths in 2020 (first wave) and 804 in 2021 (second wave). The death rate increased 2.0-fold for the obstetric (7.7 to 15.4%) and 1.6-fold for the nonobstetric groups (13.9 to 22.9%) from 2020 to 2021 (odds ratio [OR]: 0.52; 95% confidence interval [CI]: 0.47-0.58 in 2020 and OR: 0.61; 95%CI: 0.56-0.66 in 2021; p < 0.05). In women with comorbidities, the death rate increased 1.7-fold (13.3 to 23.3%) and 1.4-fold (22.8 to 31.4%) in the obstetric and nonobstetric groups, respectively (OR: 0.52; 95%CI: 0.44-0.61 in 2020 to OR: 0.66; 95%CI: 0.59-0.73 in 2021; p < 0.05). In women without comorbidities, the mortality rate was higher for nonobstetric (2.4 times; 6.6 to 15.7%) than for obstetric women (1.8 times; 5.5 to 10.1%; OR: 0.81; 95%CI: 0.69-0.95 in 2020 and OR: 0.60; 95%CI: 0.58-0.68 in 2021; p < 0.05). CONCLUSION: There was an increase in maternal deaths from COVID-19 in 2021 compared with 2020, especially in patients with comorbidities. Death rates were even higher in nonpregnant women, with or without comorbidities.

OBJETIVO: Comparar as taxas de mortalidade por COVID-19 entre gestantes ou puérperas e não gestantes durante a primeira e segunda ondas da pandemia brasileira. MéTODOS: Na presente avaliação dos dados do Sistema de Informação da Vigilância Epidemiológica da Gripe (SIVEP-Gripe), incluímos mulheres com síndrome respiratória aguda grave por COVID-19: 47.768 em 2020 (4.853 obstétricas versus 42.915 não obstétricas) e 66.689 em 2021 (5.208 obstétricas versus 61.481 não obstétricas) e estimamos a frequência de óbito intra-hospitalar. RESULTADOS: Identificamos 377 óbitos maternos em 2020 e 804 em 2021. A taxa de mortalidade por COVID-19 aumentou 2,0 vezes no grupo obstétrico (de 7,7 para 15,4%) e 1,6 vezes no grupo não obstétrico (de 13,9 para 22,9%) de 2020 a 2021 (odds ratio [OR]: 0,52; intervalo de confiança [IC] 95%: 0,47­0,58 em 2020 e OR: 0,61; IC95%: 0,56­0,66 em 2021; p < 0,05). Em mulheres com comorbidades, a taxa de óbitos aumentou 1,7 vezes (de 13,3 para 23,3%) e 1,4 vezes (de 22,8 para 31,4%) para os grupos obstétricos e não obstétricos, respectivamente (OR: 0,52; IC95%: 0,44­0,61 em 2020 para OR: 0,66; IC95%: 0,59­0,73 em 2021; p < 0,05). Em mulheres sem comorbidades, a taxa de mortalidade foi maior para as não obstétricas (2,4 vezes; de 6,6% para 15,7%) do que para mulheres obstétricas (1,8 vezes; de 5,5 para 10,1%; OR: 0,81; IC95%: 0,69­0,95 em 2020 e OR: 0,60; IC95%: 0,58­0,68 em 2021; p < 0,05). CONCLUSãO: Houve aumento das mortes maternas por COVID-19 em 2021 em relação a 2020, principalmente naquelas com comorbidades. As taxas de mortalidade foram ainda maiores em mulheres não grávidas, com ou sem comorbidades.

Cervical Cancer Screening with HPV Testing: Updates on the Recommendation.

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.

Esta atualização é uma reavaliação das "Recomendações para o uso de testes de DNA-HPV 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.

Is the HPV-test more cost-effective than cytology in cervical cancer screening? An economic analysis from a middle-income country.

OBJECTIVE: To report a modelling study using local health care costs and epidemiological inputs from a population-based program to access the cost-effectiveness of adopting hrHPV test. METHODS: A cost-effectiveness analysis based on a microsimulation dynamic Markov model. Data and costs were based on data from the local setting and literature review. The setting was Indaiatuba, Brazil, that has adopted the hrHPV test in place of cytology since 2017. After calibrating the model, one million women were simulated in hypothetical cohorts. Three strategies were tested: cytology to women aged 25 to 64 every three years; hrHPV test to women 25-64 every five years; cytology to women 25-29 years every three years and hrHPV test to women 30-64 every five years (hybrid strategy). Outcomes were Quality-adjusted life-years (QALY) and Incremental Cost-Effectiveness Ratio (ICER). RESULTS: The hrHPV testing and the hybrid strategy were the dominant strategies. Costs were lower and provided a more effective option at a negative incremental ratio of US$ 37.87 for the hybrid strategy, and negative US$ 6.16 for the HPV strategy per QALY gained. Reduction on treatment costs would influence a decrease in ICER, and an increase in the costs of the hrHPV test would increase ICER. CONCLUSIONS: Using population-based data, the switch from cytology to hrHPV testing in the cervical cancer screening program of Indaiatuba is less costly and cost-effective than the old cytology program.

Malignant Uterine Neoplasms Attended at a Brazilian Regional Hospital: 16-years Profile and Time Elapsed for Diagnosis and Treatment.

OBJECTIVE: The present study aims to evaluate the profile of endometrial carcinomas and uterine sarcomas attended in a Brazilian cancer center in the period from 2001 to 2016 and to analyze the impact of time elapsed from symptoms to diagnoses or treatment in cancer stage and survival. METHODS: This observational study with 1,190 cases evaluated the year of diagnosis, age-group, cancer stage and histological type. A subgroup of 185 women with endometrioid histology attended in the period from 2012 to 2017 was selected to assess information about initial symptoms, diagnostic methods, overall survival, and to evaluate the influence of the time elapsed from symptoms to diagnosis and treatment on staging and survival. The statistics used were descriptive, trend test, and the Kaplan-Meier method, with p-values < 0.05 for significance. RESULTS: A total of 1,068 (89.7%) carcinomas (77.2% endometrioid and 22.8% non-endometrioid) and 122 (10.3%) sarcomas were analyzed, with an increasing trend in the period (p < 0.05). Histologies of non-endometrioid carcinomas, G3 endometrioid, and carcinosarcomas constituted 30% of the cases. Non-endometrioid carcinomas and sarcomas were more frequently diagnosed in patients over 70 years of age and those on stage IV (p < 0.05). The endometrioid subgroup with 185 women reported 92% of abnormal uterine bleeding and 43% diagnosis after curettage. The average time elapsed between symptoms to diagnosis was 244 days, and between symptoms to treatment was 376 days, all without association with staging (p = 0.976) and survival (p = 0.160). Only 12% of the patients started treatment up to 60 days after diagnosis. CONCLUSION: The number of uterine carcinoma and sarcoma cases increased over the period of 2001 to 2016. Aggressive histology comprised 30% of the patients and, for endometrioid carcinomas, the time elapsed between symptoms and diagnosis or treatment was long, although without association with staging or survival.

OBJETIVO: O presente estudo avaliou o perfil dos carcinomas endometriais e sarcomas uterinos atendidos em um centro brasileiro de câncer no período de 2001 a 2016, e avaliou o impacto do tempo decorrido entre os sintomas até o diagnóstico ou tratamento no estadiamento e sobrevida pelo câncer. MéTODOS: Estudo observacional com 1.190 casos que analisou o ano do diagnóstico, faixa etária, estágio e tipo histológico do câncer. Um subgrupo de 185 mulheres com histologia endometrioide e atendidas no período de 2012 a 2017 foi selecionado para avaliar informações sobre sintomas iniciais, métodos de diagnóstico, sobrevida global e para analisar a relação entre o tempo decorrido a partir dos sintomas até o diagnóstico e tratamento no estadiamento e sobrevida. Foram realizadas análises estatísticas descritiva, de tendência linear e de sobrevida pelo método de Kaplan-Meier, com valores de p < 0,05 para significância. RESULTADOS: Os casos estudados de acordo com a histologia foram 1.068 (89,7%) carcinomas (77,2% endometrioides e 22,8% não endometrioides) e 122 (10,3%) sarcomas, com tendência crescente no período (p < 0,05). Histologias de carcinomas não endometrioides, G3 endometrioides e carcinossarcomas consistiram em 30% dos casos. Carcinomas não endometrioides e sarcomas foram mais frequentemente diagnosticados em pacientes acima de 70 anos de idade e em estágio IV (p < 0,05). O subgrupo com 185 mulheres com carcinoma endometrioide apresentou 92% de sangramento uterino anormal e 43% de diagnóstico após curetagem. O tempo médio decorrido entre os sintomas e o diagnóstico foi de 244 dias e entre os sintomas e o tratamento, 376 dias, todos sem associação com estadiamento (p = 0,976) e sobrevida (p = 0,160). Apenas 12% das pacientes iniciaram o tratamento em até 60 dias após o diagnóstico. CONCLUSãO: O número de casos de carcinomas e sarcomas uterinos aumentaram no período de 2001 a 2016. A histologia agressiva compreendeu 30% dos pacientes e, no caso dos carcinomas endometrioides, o tempo decorrido entre os sintomas e o diagnóstico ou tratamento foi longo, embora sem associação com estadiamento ou sobrevida.

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.

School-based HPV Vaccination: The Challenges in a Brazilian Initiative.

OBJECTIVE: The present study assesses the implementation and the impact after 2 years of a school-based human papillomavirus (HPV) vaccination program in a Brazilian city. METHODS: A prospective study assessing the implementation of the program, offering quadrivalent HPV vaccine in two annual doses to girls and boys aged from 9 to 10 years old. The program was started in the city of Indaiatuba, state of São Paulo, Brazil, in 2018, and had authorization from the National Immunization Program. The number of HPV vaccine first doses applied and the coverage in 2018 was calculated and compared to the year 2017. There were described events that have influenced the results. RESULTS: The program invited 4,878 children through schools (87.1% of the target population), and 7.5% refused vaccination. Several concurrent events required or competed for health professionals of the vaccination teams. The coverage of the first dose (between 9 and 10 years old) was 16.1% in 2017 and increased to 50.5% in 2018 (p < 0.0001). The first dose in all ages increased 78% in 2018 compared with 2017 (6,636/3,733). Competing demands over the program continued in 2019, and the first dose coverage dropped (26.9%). For 2020, a municipal law instituted school-based vaccination and the creation of dedicated teams for vaccination, and these strategies are waiting to be tested. CONCLUSION: School-based annual HPV vaccination in children between 9 and 10 years old was feasible and increased vaccination coverage, regardless of gender, although the program was vulnerable to competing events.

OBJETIVO: O presente estudo avalia a implantação de um programa de vacinação contra o papilomavírus humano (HPV) em escolas de uma cidade brasileira e o impacto após 2 anos. MéTODOS: Estudo prospectivo para avaliar a implementação do programa, oferecendo a vacina quadrivalente contra o HPV em duas doses anuais, para meninas e meninos de 9 a 10 anos. O programa foi autorizado pelo Programa Nacional de Imunizações na cidade de Indaiatuba, estado de São Paulo, Brasil, e teve início em 2018. A cobertura anual da primeira dose foi comparada ao ano de 2017, e os eventos que influenciaram os resultados foram descritos. RESULTADOS: O programa convidou 4.878 crianças por meio das escolas (87,1% da população-alvo) e 7,5% recusou a vacinação. Vários eventos concorrentes exigiram ou competiram pelos profissionais de saúde das equipes de vacinação. A cobertura da primeira dose (9 a 10 anos) foi de 16,1% em 2017 e aumentou para 50,5% em 2018 (p < 0,0001). A primeira dose em todas as idades aumentou 78% em 2018 em comparação com 2017 (6.636/3.733). As demandas concorrentes sobre o programa continuaram em 2019, e a cobertura da primeira dose caiu (26,9%). Para 2020, uma lei municipal instituiu a vacinação nas escolas e a criação de equipes dedicadas à vacinação, e estas estratégias aguardam para ser testadas. CONCLUSãO: A vacinação anual contra o HPV em base escolar nas idades de 9 a 10 anos foi viável e aumentou a cobertura vacinal, independentemente do gênero, embora o programa fosse vulnerável a eventos concorrentes.

Brachytherapy for stage IIIB squamous cell carcinoma of the uterine cervix: survival and toxicity.

OBJECTIVE: To compare survival and toxicity of three different treatments for stage IIIB cervix cancer: low-dose-rate (LDR), high-dose-rate (HDR) brachytherapy and association of HDR and chemotherapy. METHODS: Between 1985 and 2005, 230 patients with FIGO stage IIIB squamous cell carcinoma of the uterine cervix received 4-field pelvic teletherapy at doses between 40 and 50.4 Gy, with a different complementation in each group. The LDRB group, with 42 patients, received one or two insertions of LDR, with Cesium-137, in a total dose of 80 to 100 Gy at point A. The HDR group, 155 patients received HDR in 4 weekly 7 Gy fractions and 9 Gy to 14.4 Gy applied to the involved parametria. The CHT group, 33 patients, were given the same treatment as the HDR group and received 5 or 6 weekly cycles of cisplatin, 40 mg per m(2). RESULTS: The five-year progression-free survival (PFS) was 60% for the HDR group and 45% for the LDR group, and the two-year PFS for the CHT group was 65% (p = 0.02). The five-year Overall Survival (OS) was 65% for the HDR group and 49% for the LDR group. The two-year OS was 86% for the CHT group (p = 0.02). Rectum toxicity grade II was 7% for the LDR group, 4% for the HDR group and 7% for the CHT group that had one case of rectum toxicity grade IV. CONCLUSION: Patients that received HDR had better OS and PFS. The Chemotherapy-HDR association showed no benefit when compared to HDR only. Toxicity rates showed no difference between the three groups.

Post-radiotherapy hysterectomy does not benefit females with cervical adenocarcinoma.

Cervical adenocarcinoma is associated with a poor prognosis, which may be caused by the infiltrative growth pattern and metastasis of tumor cells. There is a lack of consensus on hysterectomy after radiotherapy for the improvement of selected cases. The present study aimed to assess the oncological outcome of post-radiotherapy hysterectomy in females with cervical adenocarcinoma. A total of 39 females with cervical adenocarcinoma at stages IB1 to IIIB, managed primarily with radiotherapy with complete response, and underwent extrafascial hysterectomy as consolidation therapy between 1988 to 2015 were studied. Surgery complications and residual disease were evaluated. A comparison group was constructed, comprising 41 females with cervical adenocarcinoma managed with exclusive radiotherapy or chemoradiotherapy demonstrating complete response, without surgery. Descriptive and survival analysis was performed. The groups were comparable in terms of age, cancer stage, radiotherapy (dose and duration) and follow-up, although 67% of hysterectomies were performed prior to 2002 and 46% of the radiotherapy group received chemoradiation. Late complications were similar. There were nine recurrences (23%) in the case series and 10 recurrences (24%) in the radiotherapy group. Residual disease was detected in 56% (22/39) of uterine specimens, of which 12 were up to 10 mm. Residual disease was associated with recurrence (31% vs. 6%, P=0.028). The overall survival rate was 75% for the case series vs. 88% for the radiotherapy group (P=0.579), and the disease-free survival rate was 79-80% for both. Removal of residual disease by hysterectomy did not improve the overall survival rate (P=0.283) and disease-free survival rate (P=0.072). Post-radiotherapy hysterectomy in cervical adenocarcinoma is a feasible procedure with acceptable complications, however, it did not bring relevant benefits in recurrences, disease-free survival, and overall survival rates.