¿Está la virtud en el punto medio? La incertidumbre del CIN2 y el papel del VPH / Is virtue at the midpoint? The uncertainty of CIN2 and the role of HPV

Objetivo: La biopsia guiada por colposcopia (BGC) marca el manejo de la neoplasia intraepitelial cervical. El objetivo de este estudio fue evaluar la concordancia de los resultados entre la BGC y la escisión amplia de la zona de transformación (LLETZ, large loop excision of the transformation zone), y la utilidad del genotipado del virus del papiloma humano (VPH) para seleccionar a las pacientes con riesgo de lesión intraepitelial escamosa de alto grado/neoplasia intraepitelial cervical 3 (HSIL/CIN3). Método: Se compararon los resultados de la BGC y de la LLETZ, siendo esta última el método de referencia. Se evaluó la relación del genotipo del VPH con el diagnóstico final de HSIL/CIN3. Resultados: La precisión de la biopsia comparada con LLETZ fue del 61,4%. La tasa de concordancia fue del 64,4% para CIN1, del 31,4% para CIN2 y del 77,4% para CIN3. La tasa global de sobrediagnóstico fue del 18,68% y la de subdiagnóstico del 19,89%. En mujeres menores de 30 años, la concordancia fue del 62,79% (CIN1 65%, CIN2 39,58% y CIN3 73,08%), la tasa de sobrediagnóstico del 22,67% y la tasa de subdiagnóstico del 15,11%. La infección por VPH16 tuvo una odds ratio de 3,86 para el diagnóstico final de HSIL/CIN3+. Conclusiones: El diagnóstico de CIN2 por BGC parece insuficiente para seleccionar a las pacientes para tratamiento escisional, principalmente en mujeres jóvenes. El hallazgo de VPH16 es un factor de riesgo de HSIL/CIN3+ independientemente del resultado de la biopsia.

Objective: Colposcopy-guided biopsy (CGB) is a basic tool for the management of cervical intraepithelial neoplasia. The aim of this study is to evaluate the concordance of results between CGB and large loop excision of the transformation zone (LLETZ), and the usefulness of human papillomavirus (HPV) genotyping to select patients at risk of H-SIL/CIN3. Method: The results of colposcopy-guided biopsy and LLETZ were compared, with LLETZ being the gold standard. The relationship of HPV genotype to the final diagnosis of CIN3 was assessed. Results: The accuracy of CGB compared to LLETZ was 61.4%. The concordance rate was 64.4% for CIN1, 31.4% for CIN2 and 77.4% for CIN3. The overall overdiagnosis rate was 18.68% and underdiagnosis rate was 19.89%. In women under 30 years of age the concordance rate was 62.79% (CIN1 65%, CIN2 39.58% and CIN3 73.08%), and the rate of overdiagnosis and underdiagnosis was 22.67% and 15.11%, respectively. HPV16 infection had an odds ratio of 3.86 for the final diagnosis of CIN3+ and the result was significant regardless of the biopsy result. Conclusions: The CGB result as CIN2 is inaccurate and seems insufficient to select patients for excisional treatment, mainly in young women. HPV16 infection is a risk factor for CIN3+ regardless of the colposcopy-guided biopsy result.

A New Brazilian Device for Cervical Cancer Screening: Acceptability and Accuracy of Self-sampling / Um Novo Dispositivo Brasileiro para Diagnóstico de Câncer Cervical: Aceitabilidade e Precisão da Autoamostragem

Abstract Objective To evaluate the accuracy and patient acceptability toward self-sampling using a new device - SelfCervix® - for detecting HPV-DNA. Methods A total of 73 women aged 25-65 who underwent regular cervical cancer screening from March to October 2016 were included. Women performed self-sampling followed by a physician-sampling, and the samples were analyzed for HPV-DNA. After that, patients were surveyed about their acceptability of self-sampling. Results HPV-DNA detection rate of self-sampling presented high accuracy and was similar to physician-collection. Sixty-four (87.7%) patients answered the acceptability survey. Most patients (89%) considered the self-sampling comfortable, and 82.5% preferred self-sampling to physician-sampling. The reasons cited were time-saving and convenience. Fifty-one (79.7%) reported that they would recommend self-sampling. Conclusion Self-sampling using the new Brazilian device SelfCervix® is not inferior in HPV-DNA detection rate compared with physician-collection, and patients are supportive of the method. Therefore, it might be an option to reach under-screened populations in Brazil.

Resumo Objetivo Avaliar a acurácia e aceitabilidade da auto-coleta utilizando um novo coletor - SelfCervix® - para a detecção de DNA de HPV. Métodos Foram incluídas no estudo 73 mulheres com idade entre 25-65 anos que realizaram seu rastreamento regular do câncer de colo do útero entre Março e Outubro de 2016. Estas mulheres realizaram a auto-coleta, seguida de coleta profissional e as amostras foram analisadas paraa presença de DNA de HPV. Após, elas responderam um questionário sobre a experiência da auto-coleta. Resultados As taxas de detecção de DNA de HPV por auto-coleta foram altas e similares as da coleta profissional. Sessenta e quatro (87,7%) pacientes responderam o questionário de experiência. A maioria (89%) considerou a auto-coleta confortável, e 82,5% preferiram o método comparado a coleta profissional. As razões citadas foram economia de tempo e conveniência. Cinquenta e uma (79,7%) mulheres confirmaram que recomendariam a auto-coleta. Conclusão Auto-coleta utilizando o novo coletor desenvolvido no Brasil não é inferior na detecção de DNA de HPV quando comparada a coleta profissional, e apresenta uma boa aceitabilidade pelas mulheres. Desta maneira, pode ser uma opção para alcançar populações que não realizam o rastreamento padrão.

Prevalence of HPV infection and cervical intraepithelial lesions in HIV positive and negative women in the city of Florianopolis / Prevalência da infecção pelo HPV e lesões intraepiteliais cervicais em mulheres HIV positivas e negativas na cidade de Florianópolis

Introduction: HPV infection is the most frequent sexually transmitted infection in women. The high oncogenic risk HPV, associated with others factors, there are a risk of progressing to a precancerous lesion of the cervix and even cancer. This evolution is related to the persistence of the infection and other factors, mainly those that interfere with the woman's immunity. The immunosuppression caused by HIV infection is an important factor for viral persistence and the appearance of these lesions. Objectives: To compare the prevalence of HPV infection and cervical intraepithelial lesions in HIV-positive and negative women and describe the possible associated risk factors. Methods: The sample consisted of 50 HIV positive women (study group) and 50 HIV negative women (control group) recruited from the public health system of Florianópolis during the months of January to April 2022. Cervical samples were collected for cytological analysis and for detection of high-risk oncogenic HPV DNA by polymerase chain reaction (PCR). Categorical variables were compared using the chi-square test, with a significance level set at 5% Results: HPV infection was more prevalent in the control group, however, HIV positive women had a higher frequency of intraepithelial lesions diagnosed on cytology. Factors such as greater number of sexual partners, depression and smoking were more frequent in the group of HIV positive women. The number of CD4 T cells less than 200 cels/mm3 was associated with a higher number of altered Pap smears and a positive HPV DNA test. The use of combination antiretroviral therapy and undetectable viral load were associated with a greater number of normal cytology and undetected HPV DNA. Conclusion: The prevalence of cervical intraepithelial lesions in HIV-infected women is higher than in women without infection. The presence of HIV infection was the most important risk factor associated with the development of cervical lesions. (AU)

Introdução: O Papilomavírus Humano (HPV) é a infecção de transmissão sexual mais frequente na mulher. O HPV de alto risco oncogênico, associado a outros fatores, apresenta risco de evoluir para uma lesão pré-cancerosa do colo de útero e até mesmo para o câncer. Essa evolução está relacionada à persistência da infecção e outros fatores, principalmente os que interferem na imunidade da mulher. A imunossupressão causada pela infecção HIV é um fator importante para a persistência viral e o aparecimento destas lesões. Objetivos: Comparar a prevalência da infecção pelo HPV e das lesões intraepiteliais do colo de útero em mulheres HIV positivas e negativas, e descrever os possíveis fatores de risco associados. Métodos: A amostra foi composta por 50 mulheres HIV positivas (grupo de estudo) e 50 mulheres HIV negativas (grupo controle) recrutadas no sistema público de saúde de Florianópolis durante os meses de janeiro a abril de 2022. Foram coletadas amostras cervicais para análise citológica e para detecção do DNA HPV de alto risco oncogênico por reação em cadeia da polimerase (PCR). As variáveis categóricas foram comparadas pelo teste qui-quadrado, com nível de significância estabelecido em 5%. Resultados: A infecção pelo HPV foi mais prevalente no grupo controle, entretanto, as mulheres HIV positivas tiveram uma maior frequência de lesões intraepiteliais diagnosticadas na citologia. Os fatores como maior número de parceiros sexuais, depressão e tabagismo foram mais frequentes no grupo de mulheres HIV positivas. O número de células TCD4 inferior a 200 células/mm3 esteve associado a maior número de colpocitologias alteradas e teste DNA HPV positivo. O uso da terapia antirretroviral combinada e a carga viral indetectável estiveram associadas a um número elevado de citologias normais e DNA HPV não detectado. Conclusão: A prevalência de lesões intraepiteliais do colo do útero em mulheres infectadas pelo HIV foi maior que em mulheres soronegativas. A presença de infecção pelo HIV foi o fator de risco mais importante associado ao desenvolvimento de lesões cervicais.Palavras-chave: HPV. HIV. coinfecção. lesões intraepiteliais escamosas cervicais. prevalência.. (AU)

Accuracy of visual inspection, cytology and colposcopy in the diagnosis of high-grade cervical intraepithelial neoplasia / Acurácia da inspeção visual, citologia e colposcopia no diagnóstico da neoplasia intraepitelial cervical de alto grau

Cervical cancer is still one of the leading causes of cancer and mortality in women, especially in low- and middle-income countries. Normally, the prevention of its occurrence is done through efficient screening and treatment programs for high-grade epithelial lesions, which are pre-malignant lesions. Cheaper diagnostic techniques ensure greater access to women, which can prevent a large number of cancer cases worldwide. Objective: The aim of the study was to evaluate the accuracy of visual inspection either with acetic acid or with Lugol's iodine, cervical cytology and colposcopy in the diagnosis of cervical intraepithelial neoplasia 2 and 3. Methods: This is a study of diagnostic accuracy. We evaluated 115 women with high-grade squamous intraepithelial lesion confirmed by biopsy, 54 with cervical intraepithelial neoplasia 2 and 61 with cervical intraepithelial neoplasia 3, from January 2016 to December 2018 at the Lower Genital Tract Pathology and Colposcopy Service of the Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. A comparative analysis of the visual inspection, Pap smear and colposcopy diagnostic methods was performed. Results: The average age was 33.1 years (standard deviation=9.83) for cervical intraepithelial neoplasia 2 cases and 35.2 years (standard deviation=7.97) for cervical intraepithelial neoplasia 3. In the cervical intraepithelial neoplasia 2 group, visual inspection tests were positive for high-grade squamous intraepithelial lesion in 98.1% of the cases with acetic acid and 94.4% with Lugol's iodine. Colposcopy identified a probable high-grade squamous intraepithelial lesion in 94.4% of the cases, while cytology only in 42.6%. In the cervical intraepithelial neoplasia 3 group, the visual inspection tests were positive for high-grade squamous intraepithelial lesion in 91.8% of the cases with acetic acid and 95.1% with Lugol's iodine. Colposcopy identified a probable high-grade squamous intraepithelial lesion in 93.5% of the cases, while cytology in 65.6%. Conclusion: Visual inspection with acetic acid and Lugol's iodine, and colposcopy test were more accurate for the diagnosis of cervical intraepithelial neoplasia 2 and 3 than through cytopathology. (AU)

Introdução: O câncer do colo de útero ainda é uma das principais causas de câncer e mortalidade em mulheres, especialmente em países de baixa e média renda. Normalmente, a prevenção de sua ocorrência é feita por meio de programas eficientes de triagem e tratamento de lesões epiteliais de alto grau, que são as lesões pré-malignas. Técnicas diagnósticas mais baratas garantem maior acesso às mulheres, podendo evitar um grande número de casos de câncer no mundo inteiro. Objetivo: O objetivo deste estudo foi avaliar a acurácia da inspeção visual (com ácido acético e com solução de lugol), da citologia cervical e da colposcopia no diagnóstico de neoplasias intraepiteliais cervicais 2/3. Métodos: Trata-se de um estudo de acurácia diagnóstica. Foram avaliadas 115 mulheres com lesão intraepitelial escamosa de alto grau confirmada por biópsia, 54 com neoplasias intraepiteliais cervicais 2 e 61 com neoplasias intraepiteliais cervicais 3, no período de janeiro de 2016 a dezembro de 2018 no Serviço de Patologia e Colposcopia do Trato Genital Inferior do Hospital de Clínicas de Porto Alegre, em Porto Alegre, Brasil. Foi realizada análise comparativa dos métodos de diagnóstico Inspeção visual com ácido acético, Inspeção visual com Solução de Lugol, colpocitologia oncótica e colposcopia. Resultados: A média de idade foi de 33,11 anos (DP 9,83) para os casos de neoplasias intraepiteliais cervicais 2 e de 35,28 anos (DP 7,97) para neoplasias intraepiteliais cervicais 3. No grupo de neoplasias intraepiteliais cervicais 2, os testes de inspeção visual foram positivos para tratamento de lesões epiteliais de alto grau em 98,1% dos casos com Inspeção visual com ácido acético e em 94,4% daqueles com Inspeção visual com Solução de Lugol. A colposcopia identificou provável tratamento de lesões epiteliais de alto grau em 94,4% dos casos, enquanto a citologia apenas 42,6%. No grupo neoplasias intraepiteliais cervicais 3, os testes de inspeção visual foram positivos para tratamento de lesões epiteliais de alto grau em 91,8% dos casos com Inspeção visual com ácido acético e em 95,1% daqueles com Inspeção visual com Solução de Lugol. A colposcopia identificou provável tratamento de lesões epiteliais de alto grau em 93,5% dos casos, enquanto a citologia em 65,6%. Conclusão: A inspeção visual (com ácido acético e com Solução de Lugol) e a colposcopia foram mais precisas para o diagnóstico de neoplasias intraepiteliais cervicais 2/3 do que a citopatologia. (AU)

Correlation and clinical significance of VISTA expression and cervical squamous cell carcinoma / 中华肿瘤杂志

Objective: To explore the relationship between the expression of the T-cell activation suppressor-immunoglobulin variable region (VISTA) and the development of cervical squamous cell carcinoma (CSCC), and the impact on the prognosis of CSCC patients. Methods: Cervical tissue samples from 116 CSCC, including 23 cervical intraepithelial neoplasia (CIN) grade I, 23 CIN grade Ⅱ-Ⅲ, and 23 chronic cervicitis patients, were collected from the First Hospital of Soochow University between March 2014 and April 2019. The expression of VISTA in each group was detected by immunohistochemistry (IHC). Survival data of CSCC patients were obtained by follow-up. The survival analysis was performed by Kaplan-Meier method, and survival differences between groups were compared by Log rank test. Prognostic impact factors were analyzed using a multifactorial Cox proportional hazards model. Results: The positive rate of VISTA expression in CSCC group was 32.8% (38/116), and which of grade Ⅱ-Ⅲ was 17.4% (4/23). VISTA expression results showed no positive expression patients in the cervical intraepithelial neoplasia grade I and chronic cervicitis groups. The differences between the CSCC group and other groups were statistically significant (P<0.01). In 116 CSCC patients, VISTA expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis (P<0.01). The mean survival time of patients in the VISTA positive expression group was 30.7 months, and the 3-year survival rate was 44.7% (17/38). However, the mean survival time of the patients in the VISTA negative expression group was 49.1 months, and the 3-year survival rate was 87.2% (68/78). The Cox regression model found that VISTA expression positivity (P=0.001) and FIGO stage (P=0.047) were prognostic factors for CSCC, and patients with VISTA-positive CSCC had a 4.130-fold risk of death higher than those with VISTA-negative expression. Conclusions: The VISTA protein is highly expressed in CSCC tissues, and its expression level is closely related to the occurrence and development of CSCC. The expression of VISTA can be used as an independent predictor of CSCC prognosis and can provide a strong basis for the treatment of CSCC with immune checkpoint inhibitors.

Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection / 中华妇产科杂志

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.

Analysis of natural regression and influencing factors of HSIL in the cervix of childbearing age patients / 中华妇产科杂志

Objective: To investigate the natural regression and related factors of high-grade squamous intraepithelial lesion (HSIL) in the cervix of childbearing age women, and to evaluate the applicability of conservative management for future fertility needs. Methods: This study included 275 patients of reproductive age with fertility needs, who were diagnosed as HSIL by biopsy from April 30, 2015 to April 30, 2022, including 229 cases (83.3%) cervical intraepithelial neoplasia (CIN) Ⅱ and 46 cases (16.7%) CIN Ⅱ-Ⅲ. They were followed-up without immediate surgery in the First Affiliated Hospital of Nanjing Medical University. The median follow-up time was 12 months (range: 3-66 months). The regression, persistence and progression of lesions in patients with HSIL were analyzed during the follow-up period, the influencing factors related to regression and the time of regression were analyzed. Results: (1) Of the 275 HSIL patients, 213 cases (77.5%, 213/275) experienced regression of the lesion during the follow-up period. In 229 CIN Ⅱ patients, 180 cases (78.6%) regressed, 21 cases (9.2%) persisted, and 28 cases (12.2%) progressed. In 46 CIN Ⅱ-Ⅲ patients, 33 cases (71.7%) regressed, 12 cases (26.1%) persisted, and 1 case (2.2%) progressed to invasive squamous cell carcinoma stage Ⅰ a1. There was no significant difference in the regression rate between the two groups (χ2=1.03, P=0.309). (2) The average age at diagnosis, age <25 years old at diagnosis were independent influencing factor of HSIL regression in univariate analysis (all P<0.05). There was no significant difference between HSIL regression and pathological grading, the severity of screening results, human papillomavirus (HPV) genotype, colposcopy image characteristics, number of biopsies during follow-up and pregnancy experience (all P>0.05). (3) The median regression times for patients aged ≥25 years and <25 years at diagnosis were 15 and 12 months, respectively. Kaplan-Meier analysis showed that age ≥25 years at diagnosis significantly increased the median regression time compared to <25 years (χ2=6.02, P=0.014). Conclusions: For HSIL patients of childbearing age, conservative management without immediate surgical intervention is preferred if CINⅡ is fully evaluated through colposcopy examination. Age ≥25 years at diagnosis is a risk factor affecting the prognosis of HSIL patients.

The characteristics and correlations of vaginal flora in women with cervical lesions / 中华肿瘤杂志

Objective: To explore the characteristics and correlations of vaginal flora in women with cervical lesions. Methods: A total of 132 women, including 41 women diagnosed with normal cervical (NC), 39 patients with low-grade cervical intraepithelial neoplasia (CIN 1), 37 patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) and 15 patients with cervical squamous cell carcinoma (SCC), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018, were enrolled in this study according to the inclusive and exclusive criteria strictly. The vaginal flora was detected by 16S rDNA sequencing technology. Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria. Results: The dominant bacteria in NC, CIN 1 and CIN 2/3 groups were Lactobacillus [constituent ratios 79.4% (1 869 598/2 354 098), 63.6% (1 536 466/2 415 100) and 58.3% (1 342 896/2 301 536), respectively], while Peptophilus [20.4% (246 072/1 205 154) ] was the dominant bacteria in SCC group. With the aggravation of cervical lesions, the diversity of vaginal flora gradually increased (Shannon index: F=6.39, P=0.001; Simpson index: F=3.95, P=0.012). During the cervical lesion progress, the ratio of Lactobacillus gradually decreased, the ratio of other anaerobes such as Peptophilus, Sneathia, Prevotella and etc. gradually increased, and the differential bacteria (LDA score >3.5) gradually evolved from Lactobacillus to other anaerobes. The top 10 relative abundance bacteria, spearman correlation coefficient>0.4 and P<0.05 were selected. Co-occurrence network analysis showed that Prevotella, Peptophilus, Porphyrinomonas, Anaerococcus, Sneathia, Atopobium, Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions, while Lactobacillus was negatively correlated with the above anaerobes. It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group. Conclusions: The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions. Peptophilus is of great significance in the diagnosis, prediction and early warning of cervical carcinogenesis.

Avaliação da função sexual e da atividade física em mulheres após tratamento do câncer de colo de útero: estudo transversal / Assessment of sexual function and physical activity in women after cervical cancer treatment: a cross-sectional study

Introdução: O tratamento do câncer do colo do útero (CCU) promove menopausa precoce em mulheres diagnosticadas durante o menacme. A consequente interrupção abrupta da produção dos hormônios ovarianos impacta na sexualidade e outras áreas da vida da mulher, inclusive sua atividade física. É possível que a atividade física influencie a atividade sexual nessas mulheres. Objetivo: Avaliar o nível de atividade física e a função sexual nas mulheres após o tratamento oncológico e verificar se a atividade física está associada a melhor função sexual. Método: Este estudo transversal incluiu mulheres tratadas para câncer do colo do útero em um hospital de referência em oncologia no Brasil, com idade entre 18 e 50 anos, submetidas a ooforectomia bilateral e/ou radioterapia pélvica há, no máximo 11 anos. O desfecho primário foi o estado da função sexual e do nível de atividade física e a correlação entre eles e o tratamento oncológico. As mulheres responderam os questionários Female Sexual Function Index (FSFI) e o International Physical Activity Questionnaire (IPAQ) por entrevista remota entre agosto de 2021 a julho de 2022. Resultados: 50 mulheres foram entrevistadas. A média de idade foi 50 anos (DP = ±5). Todas as mulheres que tinham atividade sexual apresentaram algum nível de disfunção sexual. A maior parte das mulheres era fisicamente ativa (60%). Não houve correlação do perfil de atividade física, nem da função sexual com o tratamento oncológico realizado. Não houve associação entre atividade física e maior qualidade na função sexual. Conclusão: Todas as mulheres que relataram relação sexual tinham disfunção sexual e a maioria delas era ativa fisicamente.

Background: Cervical cancer (CC) treatment promotes early menopause in women diagnosed during menacme. The consequent abrupt interruption of the production of ovarian hormones impacts on sexuality and other areas of a woman's life, including her physical activity. It is possible that physical activity influences sexual activity in these women. Aim: To evaluate the level of physical activity and sexual function in women after cancer treatment and to verify whether physical activity is associated with better sexual function. Method: This cross-sectional study included women aged between 18 and 50 years treated for cervical cancer at a reference hospital in oncology in Brazil, who had undergone bilateral oophorectomy and/or pelvic radiotherapy for a maximum of 11 years. The primary outcome was sexual function status and physical activity level and understanding between them and cancer treatment. The women answered the Female Sexual Function Index (FSFI) and the International Physical Activity Questionnaire (IPAQ) by remote interview between August 2021 and July 2022. Results: 50 women were interviewed. The mean age was 50 years (SD = ±5). All women who had sexual activity had some level of sexual dysfunction. Most women were physically active (60%). There was no change in the physical activity profile or sexual function with the oncological treatment performed. There was no association between physical activity and better quality of sexual function. Conclusion: All women who reported sexual intercourse had sexual dysfunction and most of them were physically active.

Tamizaje con citología anal en mujeres con lesiones premalignas del cuello uterino / Anal cytology screening in women with premalignant lesions of the uterine cervix / Rastreamento de citologia anal em mulheres com lesões pré-malignas do colo do útero

Objetivo: nuestro objetivo principal fue evaluar la prevalencia de citología anal patológica en mujeres con antecedentes de neoplasia intraepitelial cervical. Métodos: se trata de un estudio de cohorte transversal desde mayo de 2018 a agosto de 2020 en el Centro Hospitalario Pereira Rossell. Se estudiaron dos cohortes: una de mujeres que tenían diagnóstico de neoplasia intraepitelial cervical y otra de control de mujeres sanas que asistieron al control, con una proporción de 2:1. Se calculó un tamaño muestral total de 205 pacientes, siendo 135 pacientes con NIC con un IC del 95%, suponiendo una prevalencia del 10% de lesiones preneoplásicas anales. El tamaño muestral de la cohorte control fue de 70 pacientes según la relación preestablecida. Resultados: se encontró asociación entre la presencia de lesiones premalignas cervicales y anomalías epiteliales detectadas en la citología anal, con un cociente de prevalencia de 1,77 (IC del 95%: 1,19-2,62) y un odds ratio de 2,69 (1,36-5,30). No se encontraron diferencias significativas en las variables de raza, tipo de relación sexual o tabaquismo. Conclusiones: nuestro estudio concluye que existe una asociación entre la neoplasia intraepitelial cervical relacionada con el VPH y la citología anal patológica.

Objective: the main objective of the study was to assess the prevalence of anal cytology in women with a history of cervical intraepithelial neoplasia. Method: cohort transversal study conducted from May, 2018 until August, 2020 at Pereira Rossell Hospital. Two cohorts were studied, one of which included women with a diagnosis of cervical intraepithelial neoplasia and the other one included healthy women who attended their routine follow up, in a 2:1 ratio. The total size of the sample was 205 patients, 135 of which were patients with cervical intraepithelial neoplasia (confidence interval being 95%), presuming a 10% prevalence of anal pre-neoplasic lesions. The sample size of the control cohort was 70 patients as per the pre-defined ratio. Results: a association was found between the presence of malignant lesions of the cervix and epithelial anomalies detected in the anal cytology, with a prevalence coefficient of 1.77 (CI: 95%: 1,19 - 2,62) and odds ratio of 2,69 (1,36 - 5,30). No significant differences were found between race, type of sexual relationships or smoking variables. Conclusions: our study concludes there is an association between cervical intraepithelial neoplasia related to HPV and pathological anal screening.

Objetivo: Avaliar a prevalência de citologia anal patológica em mulheres com história de neoplasia intraepitelial cervical. Métodos: Trata-se de um estudo de coorte transversal de maio de 2018 a agosto de 2020, no Hospital Pereira Rossell. Foram estudadas duas coortes, uma de mulheres com diagnóstico de neoplasia intraepitelial cervical e outra de controle de mulheres saudáveis que compareceram ao controle na proporção de 2:1. Foi calculada uma amostra total de 205 pacientes, 135 pacientes com NIC com um IC de 95%, assumindo uma prevalência de 10% de lesões pré-neoplásicas anais. O tamanho da amostra da coorte controle foi de 70 pacientes de acordo com a relação pré-estabelecida. Resultados: Foi encontrada associação entre a presença de lesões pré-malignas cervicais e anormalidades epiteliais detectadas na citologia anal, com razão de prevalência de 1,77 (IC 95%: 1,19 - 2,62) e odds ratio 2,69 (1,36-5,30). Não foram encontradas diferenças significativas nas variáveis raça, tipo de relação sexual ou tabagismo. Conclusões: Nossos resultados mostram uma associação entre neoplasia intraepitelial cervical relacionada ao HPV e citologia anal patológica.

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.

Preventing Uterine Cervix Cancer: The Clinical Meaning of Atypical Glandular Cells / Prevenção do câncer do colo uterino: Significado clínico das células glandulares atípicas

Abstract Objective To determine the prevalence of the atypical glandular cells (AGCs) cytology and to analyze its clinical significance in different age ranges. Methods Retrospective observational study using computerized data from the Brazilian National Cancer Institute, including women screened between January 2002 and December 2008. The women included were those with an AGC result who were properly followed-up with colposcopy and a second cytology. Results A total of 132,147 cytopathological exams were performed during the study period. Five-hundred and thirty-three (0.4%) women with AGC cytology were identified and, of these, 69.41% (370/533) were properly referred for colposcopy and a new cytology. Most of the women (79.2%) with a 1st or 2nd AGC cytology were between the ages of 25 and 54 years. The 2nd cytology demonstrated 67.6% (250/370) of normality, 24.5% (91/370) of squamous atypia, and 6.2% (23/370) of AGC, 0.8% (3/370) adenocarcinoma in situ and 0.8% (3/370) adenocarcinoma invasor. On biopsy of the women with a second AGC cytology, 43.4% (10/23) had normal histology, 43.4% (10/23) had squamous lesions, 8.7% (2/23) had invasive adenocarcinoma, and 1.2% (1/23) had an inconclusive report. All of the women with high-grade squamous intraepithelial lesion (HSIL) or invasive adenocarcinoma (respectively 5 and 2 patients), after a 2nd AGC cytology were 25 years old or older. Conclusion The prevalence of the AGC cytology was low in the studied population. Most of the AGC cytology cases occurred in adult women between the ages of 25 and 54. Although most of the patients had normal histology after follow-up, several of them presented with squamous intraepithelial lesions or invasive adenocarcinoma.

Resumo Objetivo Determinar a prevalência de citologia com laudo de células glandulares atípicas (AGCs, na sigla em inglês) e analisar a significância clínica nas diferentes faixas etárias Métodos Estudo observacional retrospectivo, usando os dados arquivados no sistema do Instituto Nacional de Câncer no Brasil, que incluiu mulheres rastreadas entre janeiro de 2002 a dezembro de 2008. As mulheres incluídas tinham citologia com resultado de AGCs, que foram acompanhadas com colposcopia e nova citologia Resultados Um total de132,147 exames citopatológicos foram incluídos durante o período de estudo. Quinhentas e trinta e três mulheres com citologia de AGC foram identificadas e destas, 69.41% (370) foram encaminhadas para colposcopia e nova citologia. A prevalência de citologia de AGC na população estudada foi 0.4%. A maioria das mulheres (79.22%) com resultado citológico de AGC tinham idade entre 25 e 54 anos. A segunda citologia demonstrou 67.56% (250/370) de normalidade, 24.5% (91/370) de atipias escamosas, e 6.2% (23/370) de AGC. Na biopsia das mulheres com a 2ª citologia de AGC, 43.4% (10/23) tinham histologia normal, 43.4% (10/23) tinha lesões escamosas, 8.7% (2/23) tinha adenocarcinoma invasor e 1.2% (1/23) tinha laudo inconclusivo. Todas as mulheres com lesões intraepiteliais escamosas de alto grau (HSIL, na sigla em inglês) ou adenocarcinoma invasor (respectivamente 5 e 2pacientes), após a 2ª citologia com AGC, tinham 25 anos de idade ou mais. Conclusão A prevalência de citologia com AGC foi baixa na população estudada. Muitos casos de citologia com AGC apareceram em mulheres adultas, entre 25 e 54 anos de idade. Embora a maioria das pacientes tiveram histologia normal após seguimento, várias apresentaram lesões intraepiteliais escamosas ou glandulares invasoras.

Cervical Intraepithelial Neoplasia: Analyzing the Disease Present Exclusively in the Endocervical Canal / Neoplasia intraepitelial cervical: Analisando a doença presente exclusivamente no canal endocervical

Abstract Objective To evaluate the role of cervical cytology (Pap smear) in the diagnosis of cervical intraepithelial neoplasia 2 or greater (CIN2+), presented exclusively in the endocervical canal, the clinical-epidemiological characteristics of this lesion, the necessary length of canal to be removed to treat, and the rate of invasive lesion hidden in the endocervical canal. Methods Cross-sectional study, by database analysis, of patients with abnormal cytology (high-grade squamous intraepithelial lesion [HSIL]), without visible colposcopy lesion, submitted to loop electrosurgical procedure (LEEP) to evaluate the association of cytology results with the histological product of the conization, to identify the epidemiological characteristics of endocervical lesion and clinical evolution, using a pvalue< 0.05 and 95% CI. Results In 444 cases, the Pap smear sensitivity for CIN2+ diagnosis was 75% (95% CI: 69.8-79.7), specificity was 40% (95% CI: 30.2-49.5), and the prevalence rate of histological lesion was 73% (95% CI: 70.1-78.7). There was a higher prevalence of CIN2+ in women over 42 years old and invasive cancer in those over 56 years old (p<0.001), and it was necessary to remove 2.6 cm in length of the canal to reduce the chance of recurrence (p<0.006). The rate of invasive cancer was 2.7%. Conclusion Cytology was related to a high prevalence to histological lesion (73%) in the diagnosis of CIN2+ in the endocervical disease; older patients presented a higher relationship with histological lesions in the canal disease, and it was necessary to remove an average of 2.6 cm in length of the endocervical canal to avoid the persistence and progression of CIN. The rate of occult neoplasia in the endocervical canal was 2.7%.

Resumo Objetivo Avaliar o papel da citologia oncótica (CO) no diagnóstico da neoplasia intraepitelial cervical 2 ou maior (NIC2+) presente exclusivamente no canal endocervical, as características clínico-epidemiológicas deste tipo de lesão, o comprimento necessário de canal a ser retirado na conização, e a taxa de lesão invasora oculta no canal endocervical. Métodos Estudo transversal, por análise de base de dados, de pacientes comcitologia alterada, sem lesão colposcópica visível, submetidas a conização por cirurgia de alta frequência (CAF), para avaliar a associação dos resultados citológicos com o produto histológico da conização, as características epidemiológicas da lesão endocervical, e evolução clínica, utilizando o valor de p<0.05 e intervalo de confiança (IC) de 95%. Resultados Nos 444 casos analisados, a sensibilidade da CO para o diagnóstico de NIC 2+ foi de 75% (IC 95%: 69.8-79.7), a especificidade foi de 40% (IC 95%: 30.2-49.5), e a taxa de prevalência de lesão histológica foi de 73% (IC 95%: 70.1-78.7). Houve maior prevalência de NIC2+ em pacientes com mais de 42 anos de idade e de neoplasia invasora naquelas commais de 56 anos (p<0.001), e foi necessário a retirada de 2.6 cm de comprimento de canal para diminuir a taxa de recidiva (p<0.006). Foi identificada uma taxa de 2.7% de neoplasia invasora. Conclusão A citologia esteve relacionada a uma alta prevalência de lesão (73%) no diagnóstico das NIC2+ na doença endocervical; quanto maior a idade, maior foi a relação da histologia com a citologia de canal, e se fez necessário retirar uma média de 2.6 cmde comprimento de canal para evitar a persistência e a progressão da NIC. A taxa de neoplasia oculta no canal endocervical foi 2.7%.

When is There no Benefit in Performing a Biopsy in the Suspicion of Intraepithelial Lesions of the Cervix? / Quando não há benefício em realizar biópsia na suspeita de lesões intraepiteliais do colo uterino?

Abstract Objective To evaluate whether colposcopy-directed biopsy is necessary to increase the accuracy of diagnosing cervical intraepithelial lesions in relation to colposcopy. Methods We performed a retrospective, observational study by analyzing medical records obtained fromHospital de Clínicas do Paraná fromFebruary 2008 to February 2018. Patients with results of Pap tests, colposcopy, colposcopy-directed biopsy, and surgical procedures (high-frequency surgery or cold conization) were included. Data such as quadrants involved during colposcopy and age differences were also analyzed. Results A total of 299 women were included. Colposcopy was found to have an accuracy rate of 76.25% (95% confidence interval [CI], 71.4-81.1). Among the highest-grade lesions, the accuracy rate was 80.5% (95% CI, 75.7-85.3). The accuracy rates for biopsy were 79.6% (95% CI, 75-84.2) and 84.6% (95% CI, 80-89.1) for the highest-grade lesions. High-grade lesions were accurately confirmed in 76.9% and 85% of patients with 1 and 2 or more affected quadrants, respectively. For women younger than 40 years, the accuracy rates were 77.6% and 80.8% for colposcopy and biopsy, respectively. For women 40 years or older, the accuracy rates were 72.5% and 76.3% for colposcopy and biopsy, respectively. Conclusion There is no difference between the accuracy of colposcopy and that of biopsy in diagnosing cervical intraepithelial lesions in relation with the result of conization. The patients who received the greatest benefit when biopsy was not performed were those with high-grade lesions at colposcopy, a lesion involving 2 or more quadrants, and those younger than 40 years.

Resumo Objetivo Avaliar se a biópsia colpodirigida é necessária para aumentar a acurácia diagnóstica nas lesões intraepiteliais de colo uterino em relaçãoà colposcopia. Métodos Estudo retrospectivo, observacional, incluindo pacientes submetidas a colposcopia, biópsia colpodirigida, e procedimento cirúrgico (cirurgia de alta frequência ou conização a frio), no período de fevereiro de 2008 a fevereiro de 2018, no Hospital de Clínicas da Universidade Federal do Paraná. Dados como número de quadrantes da lesão presentes na colposcopia, número de fragmentos retirados nas biópsias e diferenças por idade também foram analisados. Resultados Um total de 299 mulheres foram incluídas. Foi encontrada uma acurácia de 76,25% (intervalo de confiança [IC] 95% 71,4-81,1) entre a colposcopia e a conização, sendo 80,5% % (IC 95% 75.7-85.3) nas lesões de maior grau. A acurácia da biópsia foi de 79,6% (IC 95% 75-84,2), sendo 84,6% (IC 95% 80-89,1) nas lesões de maior grau. Pacientes com 1 quadrante acometido tiveram confirmação de 76,9% nas lesões de maior grau, enquanto as com 2 quadrantes acometidos apresentaram o mesmo resultado em 85% dos casos. A acurácia com a biópsia de 1 fragmento foi de 78% e com2 ou mais fragmentos 80%. Paramulheres com menos de 40 anos, a acurácia foi de 77,6% e 80,8% para colposcopia e biópsia, respectivamente. Para mulheres com 40 anos ou mais, a acurácia foi de 72,5% e 76,3% para colposcopia e biópsia, respectivamente. Conclusão Não há diferença entre a acurácia da colposcopia e a da biópsia colpodirigida no diagnóstico de lesões intraepiteliais cervicais em relação ao resultado da conização. As pacientes que tiveram o maior benefício quando a biópsia não foi realizada foram as que apresentaram lesão de alto grau na colposcopia e aquelas com menos de 40 anos, não existindo benefício emrealizar biópsia previamente a conização neste grupo de pacientes.

A importância dos fatores associados a não adesão ao exame preventivo do câncer de colo uterino por mulheres brasileiras ­ revisão sistemática / The importance of factors associated with non-adherence to preventive screening for cervical cancer by Brazilian women ­ systematic review

Objetivo: O presente estudo busca avaliar a importância da adesão ao exame de Papanicolaou no diagnóstico do Papilomavírus humano, bem como relatar as dificuldades e os fatores da não realização do mesmo por mulheres brasileiras. Métodos: revisão sistemática da literatura mediante busca de artigos indexados nas plataformas eletrônicas de dados PubMed, BVS-Brasil e SciELO, entre os anos de 2008 a 2018. Resultados: No total foram encontrados 1.458 artigos nas bases de dados selecionadas, foram excluídos 1.411 artigos, os quais se enquadraram nos critérios de exclusão, e 38 duplicatas. Ao final do total de artigos analisados foram incluídos 10 para a realização da síntese quali-quantitativa. Considerações finais: A partir dos artigos analisados pode-se observar que as diferenças entre raça, classe econômica, nível de escolaridade e estado civil mostram-se como fatores determinantes quando comparamos a diferença na adesão e acesso do exame de Papanicolaou entre as mulheres brasileiras. Faz-se necessária a utilização de ações, campanhas e estratégias para a melhoria na realização do exame, enfatizando a sua importância.

Objective: The present study aims to evaluate the importance of the adhesion of the Pap smear technique to the diagnosis of the human papillomavirus, as well as to report the difficulties and factors of noncompletion by Brazilian women. Methods: systematic review of the literature by searching articles indexed in the electronic platforms of data PubMed, BVS-Brazil and Scielo, between the years of 2008 to 2018. Results: In total, 1,458 articles were found in the selected databases, 1,411 articles were excluded, as these were included in the exclusion criteria and 38 duplicates. At the end of the total of analyzed articles, 10 were included for the accomplishment of the qualitative-quantitative synthesis. Final considerations: From the analyzed articles, it can be observed that the differences between race, economic class, schooling level and marital status are determining factors when comparing the difference in the adhesion and access of the Pap test among Brazilian women. It is necessary to use actions, campaigns and strategies for improving the exam, emphasizing the importance of taking the exam.

Analysis of the Excess of Papanicolaou Tests in Brazil from 2006 to 2015 / Análise do excesso de testes de Papanicolaou no Brasil entre 2006 e 2015

Abstract Objective To analyze the quantity of cervical smears, also designated Papanicolaou tests, between 2006 and 2015 in all the Federal units of Brazil, as well as to verify the quantity of exams collected outside the recommended age range and the economic impact of such excess. Methods The data was collected from the Ministry of Health's database called Sistema de Informação do Câncer do Colo de Útero (SISCOLO), which contains all the test results collected nationwide by the Unified Health System (SUS, in the Portuguese acronym). From that, the number of exams and the age range of thewomen who underwent them were analyzed; besides, these numbers were stratified according to the state of where the exam was performed. The quantity of exams collected outside the recommended age range was verified, and, so, the economic impact generated was noted. Results Between 2006and2015, 87,425,549Papanicolaoutestswere collected in Brazil. Of these, 20,215,052 testswere collected outside the age range recommended by the Brazilian Ministry of Health; this number corresponded to 23.12% of all exams. From such data, considering that each Pap smear collected by SUS generates a cost of BRL 7.30 to the government, according to the information in the Tabela SUS dated September 2018, there was a total charge of BRL 147,569,880 for tests collected outside the protocol. Conclusion In Brazil, according to the Ministry of Health's protocol about the recommended practices on collecting Pap smears, whose newest edition dates of 2016, it is recommended that Pap smears are collected inwomen from a specific age range, inwhom the potential diagnosing advantages overcome the onus of overdiagnosis or of a lesion with great regression potential. However, such protocols have not been correctly followed, promoting more than 20 million tests in excess, and an exorbitant cost for the Brazilian public health system. It is relevant to take measures to correctly use the official protocol, reducing the patients risks, as well as the economic impact for SUS.

Resumo Objetivo Analisar a quantidade de exames cérvico-vaginais, também chamados de Teste de Papanicolau, entre os anos de 2006 e 2015 em todos os estados brasileiros, bem como verificar o número de exames realizados fora da faixa etária indicada, e o impacto econômico desse excesso. Métodos Os dados foram coletados a partir da base de dados do Ministério da Saúde chamada Sistema de Informação do Câncer do Colo de Útero (SISCOLO), que reúne os resultados de exames realizados em todo o Brasil pelo sistema único de saúde (SUS). A partir disso, foi analisado o número de exames e a faixa-etária de realização dos mesmos; além disso, esses números foram estratificados de acordo com o estado brasileiro de origem do exame. Foi verificada a quantidade de exames fora da idade recomendada, e, assim, foi observado o impacto econômico gerado. Resultado Entre 2006 e 2015, 87.425.549 exames de Papanicolau foram realizados no Brasil. Deste montante, 20.215.052 testes foram realizados fora da faixa-etária preconizada pelo Ministério da Saúde do Brasil, o que equivale a 23,12% do total. A partir desse número, considerando que cada exame cérvico -vaginal realizado pelo SUS gera um custo de R$ 7,30 para o governo, de acordo com informações na Tabela SUS datada de setembro de 2018, foram gastos R$ 147.569.880 em exames realizados sem indicação. Conclusão No Brasil, no protocolo do Ministério da Saúde sobre as práticas adequadas em coleta de exames cérvico-vaginais, sendo sua edição mais recente de 2016, a recomendação é realizar o teste de Papanicolau em mulheres dentro de uma faixaetária específica, na qual a chance de se diagnosticar uma lesão supera o ônus de um sobrediagnóstico ou uma lesão com grande potencial de regressão. Entretanto, essa recomendação não tem sido seguida corretamente, gerando mais de 20 milhões de exames excedentes e umcusto monetário exorbitante para o sistema público de saúde. É importante que medidas sejam tomadas para que o protocolo seja empregado corretamente a fim de reduzir riscos para a paciente, bem como a redução de gastos desnecessários para o SUS.

A nested case-control study on the relationship between red blood cell folate and the prognosis of low-grade cervical intraepithelial neoplasia / 中华预防医学杂志

Objective: To evaluate the relationship between red blood cell folate (RBC folate) and the prognosis of low-grade cervical intraepithelial neoplasia (CIN 1). Methods: In the married women cohort established in 2014, 564 women with CIN 1 diagnosed by pathology were recruited. The demographic characteristics and factors of cervical intraepithelial neoplasia were collected. Meanwhile, the infection status of human papillomavirus (HPV) was detected by molecular diversion hybridization, and the level of RBC folate was measured by chemical photoimmunoassay. After 24 months of follow-up, pathological examination was performed again to observe the prognosis of participants. The women with reversal were taken as the control group,and those with continuous and progressive CIN 1 were taken as the case group respectively. The relationship between RBC folate and CIN 1 outcome was evaluated by logistic regression model. Results: 453 women completed the follow-up, aged (49.72±6.84) years old. CIN 1 was reversed in 342 women, continued in 58 cases and progressed in 53 cases. The RBC folate level M (Q1,Q3) were 399.01 (307.10, 538.97) ng/ml, 316.98 (184.74, 428.49) ng/ml and 247.14 (170.54, 348.97) ng/ml, respectively. With the decrease of RBC folate, the risk of continuous and progressive CIN 1 increased (all P<0.001), while the risk of reversal CIN 1 decreased gradually (P<0.001). Combined with high-risk human papillomavirus (HR-HPV) infection status, low level of RBC folate could increase the risk of CIN 1 progression regardless of HR-HPV infection (HR-HPV infection: OR=21.34, 95%CI: 3.98-114.54; HR-HPV uninfection: OR=11.15, 95%CI: 2.34-53.13). Conclusion: Low level of RBC folate could increase the risk of CIN 1 persistence and progression regardless of HR-HPV infection.

Performance of point-of-care testing for cervical cancer screening / 中华预防医学杂志

Objective: To evaluate the performance of point-of-care testing for cervical cancer and precancerous lesions screening. Methods: In September 2020, 197 and 273 women were selected by using simple random sampling method from "self-sampling" cohort and "physician-sampling" cohort established in Xiangyuan county, Shanxi Province, China, respectively. Cervical exfoliated cells were collected by women themselves or gynecologists. All samples were detected by POCT and women with positive result were directly referred for colposcopy. Subsequently, all the samples were detected by careHPV and PCR test. Colposcopy and punch biopsy were performed for women with POCT negative but careHPV or PCR test positive at another visit. Using histopathological diagnosis as the gold standard, we calculated sensitivity, specificity and drew the receiver operating characteristic (ROC) curves. The accuracy of POCT was analyzed and compared to that of careHPV and conventional PCR test in cervical cancer and precancerous lesions screening. Results: The median (Q1 , Q3) age of 470 women was 51 (45, 57) years old. Based on self-sampling, the sensitivity and specificity of POCT for CIN2+ were 100.00% (95%CI: 56.56%-100.00%) and 28.95% (95%CI: 22.97%-35.76%), respectively. Compared with POCT, POCT HPV16/18 test had similar sensitivity and higher specificity of 89.47% (95%CI: 84.30%-93.08%). Self-sampling POCT HPV16/18 test had an AUC of 0.947 (95%CI:0.910-0.985), which was higher than that of careHPV and PCR test. Physician-sampling POCT test had 100.00% sensitivity (95%CI: 64.57%-100.00%) and 55.85% specificity (95%CI: 49.83%-61.70%) for detecting CIN2+. POCT HPV16/18 test had lower sensitivity (71.43%, 95%CI: 35.90%-91.76%) and higher specificity (92.45%, 95%CI: 88.63%-95.06%). POCT HPV16/18 test generally showed similar AUC on both self-collected samples and clinician-collected samples (0.947 vs 0.819, P=0.217). Conclusion: POCT HPV16/18 test is an effective method with relatively high sensitivity and specificity for cervical cancer screening.

Clinical research progress and implications of therapeutic vaccines for cervical cancer and precancerous lesions: a qualitative systematic review / 中华肿瘤杂志

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.

Coordenação do cuidado na Atenção Primária: gravidez, câncer de colo uterino e de mama como marcadores / Pregnancy, cervical cancer and beast cancer as markers of primary care coordination / Coordinación del cuidado en la atención primaria: embarazo, cáncer de cuello uterino y de mama como marcadores

O estudo buscou compreender a coordenação do cuidado pela Atenção Primária à Saúde para casos de gestação, câncer de mama e de colo uterino. O atributo foi entendido como a responsabilidade que os profissionais das equipes de Saúde da Família (eSF) têm em coordenar a atenção prestada aos usuários ao longo da rede de atenção, assumindo o acompanhamento continuado e a identificação de necessidades. De modo geral, foram identificadas ações de coordenação do cuidado mais bem estruturadas nas ações internas em nível primário, sobretudo aquelas de atenção às gestantes. Quando o trabalho de coordenação envolvia a rede, o destaque foi para a ausência da contrarreferência e para a informalidade nos processos de continuidade da atenção.(AU)

The aim of this study was to understand the coordination of primary health care for pregnant women and breast and cervical cancer patients. The attribute was understood as the responsibility family health care workers have for coordinating care delivery, including continuous follow-up and the identification of patient needs. Overall, the findings show that care coordination was better structured at internal primary care level, particularly pregnancy care. When coordination involved the care network, the findings highlight lack of counter-referral and informal processes for the continuity of care.(AU)

El objetivo del estudio fue entender la coordinación del cuidado por parte de la Atención Primaria de la Salud para casos de gestación, cáncer de mama y de cuello uterino. El atributo fue entendido como la responsabilidad que los profesionales de los equipos de salud de la familia tienen para coordinar la atención prestada a los usuarios en la red de atención, asumiendo el acompañamiento continuado y la identificación de necesidades. Por lo general, se identificaron acciones de coordinación del cuidado mejor estructuradas en las acciones internas en el nivel primario, principalmente para aquellas de atención a las gestantes. Cuando el trabajo de coordinación envolvía la red, el destaque fue para la ausencia de la contrarreferencia y para la informalidad en los procesos para la continuidad de la atención.(AU)