Genital Human Papillomavirus Infection in women from Florianópolis - Santa Catarina, Brazil / Infecção genital pelo Papilomavírus Humano em mulheres de Florianópolis - Santa Catarina, Brasil

Introduction: Human Papillomavirus (HPV) infection is the most common sexually transmitted infection in women. About 80% of sexually active women will have contact with this virus at some age in their lives. Most infections will be transient, but when the infection becomes persistent, associated with high oncogenic risk HPV, there may be progression to cancer, especially cervical cancer. The best way to prevent HPV infection is through the use of vaccines. Objective: To assess which are the most prevalent types of HPV in the city of Florianópolis, Brazil and if the majority of the diagnosed types are contained in the HPV vaccines currently available on the market and in the public health sector. Methods: More than 14,727 HPV tests were evaluated for the diagnosis of genital HPV infection in women from Florianópolis. The prevalence of infection was evaluated according to age of the women. HPV detection was performed using molecular biology tests, such as hybrid capture (for diagnosis of the HPV group, high or low oncogenic risk) and PCR (viral genotyping) techniques. Results: The diagnosis of HPV infection was made for women between one and 102 years of age. The highest positivity of the exams was observed in women aged 20­25 years (51% of the exams). The most prevalent age group was 31­35 years old (23.5%), and the lowest was for women aged 70 and above (0.6%). High oncogenic risk HPV was detected in 94.1% of positive samples and was the most frequent in all age groups. Mixed infection (high- and low-risk HPV) was more prevalent in the 66­70 age group (25.6%). The most frequent genotypes were non-16/18 high oncogenic risk HPV (77% of positive cases). HPV 16 was found in 17.1% of positive cases, and HPV 18 in 6.5%. Conclusion: The most prevalent types of HPV in Florianópolis in the last 6 years are non-16/18 high oncogenic risk HPV types, viral types not covered by the current HPV vaccine available in the public health sector in Brazil.

Introdução: A infecção pelo Papilomavírus Humano (HPV)é a infecção sexualmente transmissível mais frequente na mulher. Cerca de 80% das mulheres sexualmente ativas irão entrar em contato com este vírus em algum momento da sua vida. A maioria das infecções será transitória, mas quando a infecção se torna persistente, associada aos HPV de alto risco oncogênico, poderá haver a progressão para o câncer, principalmente o câncer de colo de útero. A melhor forma de prevenção da contaminação pelo HPV é através da utilização das vacinas. Objetivo: Avaliar quais são os tipos de HPV mais prevalentes na cidade de Florianópolis, Brasil, e se a maioria dos tipos diagnosticados estão contidos nas vacinas contra o HPV atualmente disponíveis no mercado e no setor público de saúde. Métodos: Foram avaliados 14.727 exames para diagnóstico da infecção genital pelo HPV em mulheres de Florianópolis, de acordo com a idade das mulheres. A detecção do HPV foi realizada através dos exames de biologia molecular pelas técnicas de captura híbrida (para diagnóstico do grupo de HPV, alto ou baixo risco oncogênico) e PCR (genotipagem viral). Resultados: Foram avaliados exames para diagnóstico da infecção de mulheres entre um e 102 anos de idade. A maior positividade dos exames foi observada em mulheres dos 20­25 anos (51% dos exames). A faixa etária de maior prevalência foi dos 31­35 anos (23,5%), e a menor, após os 70 anos (0,6%). O HPV de alto risco oncogênico foi detectado em 94,1% dos casos positivos e foi o mais frequente em todas as faixas etárias. A infecção mista (HPV de alto e baixo risco) foi mais prevalente na faixa etária dos 66­70 anos (25,6%). Os genótipos mais frequentes foram os HPV de alto risco oncogênico não 16/18 (77% dos casos positivos). O HPV 16 foi encontrado em 17,1% dos casos positivos, e o HPV 18 em 6,5%. Conclusão: Os tipos de HPV mais prevalentes em Florianópolis nos últimos 6 anos são os HPV de alto risco oncogênico não 16/18, tipos virais não cobertos pela atual vacina contra o HPV disponível no setor público de saúde do Brasil.Palavras-chave: HPV. Tipos de HPV. Câncer de colo de útero. Cobertura vacinal.

Variabilidade espacial intraurbana da mortalidade por câncer de mama e do colo do útero no município de São Paulo: análise dos fatores associados / Intra-urban spatial variability of breast and cervical cancer mortality in the city of São Paulo: analysis of associated factors

RESUMO Objetivo: Identificar a variabilidade espacial da mortalidade por câncer de mama e colo do útero e avaliar fatores associados à mortalidade por esses cânceres no município de São Paulo. Métodos: Entre 2009 e 2016 foram registrados, no Sistema de Informações sobre Mortalidade, 10.124 óbitos por câncer de mama e 2.116 óbitos por câncer do colo do útero em mulheres com 20 anos e mais. Os registros foram geocodificados por endereço de residência e agregados segundo território adstrito. Foram realizadas modelagens de regressão espacial utilizando-se a abordagem bayesiana com estrutura de Besag-York-Mollié para verificar a associação dos óbitos com indicadores selecionados. Resultados: As taxas de mortalidade por esses cânceres apresentaram padrões espaciais inversos. As variáveis associadas à mortalidade por câncer de mama foram: tempo de deslocamento para o trabalho entre uma e duas horas (risco relativo — RR 0,97; intervalo de credibilidade — IC95% 0,93-1,00); mulheres responsáveis pelo domicílio (RR 0,97; IC95% 0,94-0,99) e óbitos por câncer de mama ocorridos em estabelecimentos privados (RR 1,04; IC95% 1,00-1,07). À mortalidade por câncer do colo do útero, estiveram associados: tempo de deslocamento para o trabalho entre meia e uma hora (RR 0,92; IC95% 0,87-0,98); rendimento domiciliar até três salários-mínimos (RR 1,27; IC95% 1,18-1,37); e razão de menores de um ano em relação à população feminina de 15 a 49 anos (RR 1,09; IC95% 1,01-1,18). Conclusão: Foram calculados os RR preditos para a mortalidade por esses cânceres, que estiveram associados às condições socioeconômicas das áreas de abrangência.

ABSTRACT Objective: To identify spatial variability of mortality from breast and cervical cancer and to assess factors associated in the city of São Paulo. Methods: Between 2009 and 2016, 10,124 deaths from breast cancer and 2,116 deaths from cervical cancer were recorded in the Mortality Information System among women aged 20 years and over. The records were geocoded by address of residence and grouped according to Primary Health Care coverage areas. A spatial regression modeling was put together using the Bayesian approach with a Besag-York-Mollié structure to verify the association of deaths with selected indicators. Results: Mortality rates from these types of cancer showed inverse spatial patterns. These variables were associated with breast cancer mortality: travel time between one and two hours to work (RR - relative risk: 0.97; 95%CI - credible interval: 0.93-1.00); women being the head of the household (RR 0.97; 95%CI 0.94-0.99) and deaths from breast cancer in private health institutions (RR 1.04; 95%CI 1.00-1.07). The following variables were associated with mortality from cervical cancer: travel time to work between half an hour and one hour (RR 0.92; 95%CI 0.87-0.98); per capita household income of up to 3 minimum wages (RR 1.27; 95%CI 1.18-1.37) and ratio of children under one year of age related to the female population aged 15 to 49 years (RR 1.09; 95%CI 1.01-1.18). Conclusion: The predicted RR for mortality from these cancers were calculated and associated with the socioeconomic conditions of the areas covered.

Association of Swede Score and 2011 IFCPC Nomenclature in Women with Abnormal Cytology / A Associação entre o escore Swede e a nomenclatura IFCPC 2011 em mulheres com citologia anormal

Abstract Objective To assess the association between two colposcopic indices, the Swede score and the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) Nomenclature as well as to determine the efficacy of the Swede score with cutoffs of 7 and 8. Methods In the present cross-sectional pilot study, 34 women who had at least 1 colposcopy-directed biopsy due to abnormal cytology were enrolled. The colposcopic findings were scored by both the Swede score and the 2011 IFCPC Nomenclature and were compared with each other. The Kappa coefficient and the McNemar test were used. Accuracy, sensitivity, specificity, and positive and negative predictive values (NPV and PPV, respectively) were calculated, as well as the effectiveness with cutoffs of 7 and 8 in identifying cervical intraepithelial neoplasm (CIN) 2+ when using the Swede score. Results The correlation between the 2 colposcopic indices was 79.41%. The Kappa coefficient and the McNemar p-value were 0.55 and 0.37, respectively. The IFCPC Nomenclature had sensitivity, specificity, accuracy, PPV, and NPV of 85.71, 55.00, 67.64, 57.14, and 84.61%, respectively. The Swede score had sensitivity, specificity, accuracy, PPV, and NPV of 100, 63.15, 79.41, 68.18, and 100%, respectively. A Swede score cutoff of 7 for CIN 2+ detection had a specificity of 94.73%, while with a cutoff of 8 it increased to 100%. The sensitivity for both values was 60%. The PPV and NPV for cutoffs of 7 and 8 were 90 and 75 and 100 and 76%, respectively. Conclusion Although both colposcopic indices have good reproducibility, the Swede score showed greater accuracy, sensitivity, and specificity in identifying CIN 2 + , especially when using a cutoff of 8.

Resumo Objetivo Avaliar a associação entre dois índices colposcópicos, o escore Swede e a Nomenclatura International Federation of Cervical Pathology and Colposcopy (IFCPC, na sigla em inglês) 2011, assim como determinar a eficácia do escore Swede com os pontos de corte 7 e 8. Métodos Trata-se de um estudo transversal, com 34 mulheres incluídas, que realizaram colposcopia com biópsia dirigida devido a uma citologia anormal. Os achados colposcópicos foram categorizados pelo escore Swede e pela Nomenclatura IFCPC 2011 e comparados um com o outro. Foram avaliados o coeficiente Kappa e o teste de McNemar e foram calculados a acurácia, a sensibilidade, a especificidade e valores preditivos negativos e positivos (VPN e VPP, respectivamente) de cada índice, assim como a eficácia com os pontos de corte 7 e 8 do escore Swede para determinar as lesões de neoplasia intraepitelial cervical (NIC) 2 + . Resultados A concordância entre os 2 índices foi de 79,41% e o coeficiente Kappa e o valor-p do teste de McNemar foram 0.55 e 0.37, respectivamente. Pela Nomenclatura IFCPC 2011, obtivemos como sensibilidade, especificidade, acurácia, VPP e VPN, respectivamente: 85,71, 55,00, 67,64, 57,14 e 84,61%. Pelo escore Swede obtivemos como sensibilidade, especificidade, acurácia, VPP e VPN, respectivamente: 100, 63,15, 79,41, 68,18 e 100%. O uso do escore Swede para detecção das lesões NIC 2+ obteve como especificidade 94,73% com o valor de corte de 7, enquanto o valor de corte 8 obteve 100%. A sensibilidade para ambos os cortes foi de 60%. O VPP e o VPN com os cortes 7 e 8 foram, respectivamente: 90,00 e 75,00 e 100,00 e 76,00%. Conclusão Ambos os índices colposcópicos tiveram boa reprodutibilidade; no entanto, o escore Swede mostrou melhor acurácia, sensibilidade e especificidade em identificar as lesões NIC 2+ e o melhor ponto de corte para identificar as lesões NIC2+ foi com o valor 8.

Fatores associados ao início do tratamento especializado em tempo inoportuno após diagnóstico do câncer do colo do útero no Estado da Bahia, Brasil / Factores asociados con el inicio del tratamiento especializado en tiempo inadecuado tras un diagnóstico de cáncer de cuello de útero en el estado de Bahía, Brasil / Factors associated with delay in specialized treatment after diagnosis of cervical cancer in Bahia State, Brazil

Este estudo teve o objetivo de analisar os fatores associados ao tratamento especializado em tempo inoportuno após diagnóstico do câncer do colo do útero no Estado da Bahia, Brasil. Trata-se de um estudo de base hospitalar, de corte transversal, realizado com mulheres tratadas em unidades credenciadas ao sistema de Registro Hospitalar de Câncer (RHC) do Estado da Bahia, no período de 2008 a 2017. Foi realizada análise descritiva e regressão logística, construída na modelagem stepwise backward, para estimar as razões de prevalência (RP) bruta e ajustada, sendo consideradas estatisticamente significantes aquelas com o valor de p ≤ 0,05 pelo teste qui-quadrado de Pearson. Foram analisados 9.184 casos, destes, 65% tiveram tratamento em tempo inoportuno (tempo transcorrido entre o diagnóstico e o primeiro tratamento > 60 dias). A prevalência de tratamento em tempo inoportuno apresentou valores mais elevados entre mulheres com 65 anos ou mais (RP = 1,30; IC95%: 1,21-1,39), nenhuma escolaridade (RP = 1,24; IC95%: 1,15-1,33) e estadiamento avançado (RP = 1,17; IC95%: 1,13-1,21). Na maioria dos casos analisados, houve tratamento em tempo inoportuno, com maior prevalência entre as mulheres com mais idade, menor escolaridade e estadiamento clínico do tumor avançado, evidenciando a necessidade de ampliação do acesso aos serviços de tratamento oncológico no Estado da Bahia, em especial para estes grupos que apresentaram pior situação.

El objetivo de este estudio fue analizar los factores asociados al tratamiento especializado en un tiempo inadecuado, tras el diagnóstico del cáncer de cuello de útero en el estado da Bahía, Brasil. Se trata de un estudio con base hospitalaria, de corte transversal, realizado con mujeres tratadas en unidades acreditadas en el sistema de Registro Hospitalario de Cáncer (RHC) del estado de Bahía, en el período de 2008 a 2017. Se realizó un análisis descriptivo y regresión logística, construida en el modelado stepwise backward, para estimar las razones de prevalencia (RP) bruta y ajustada, siendo consideradas estadísticamente significativas aquellas con el valor de p ≤ 0,05, mediante el test chi-cuadrado de Pearson. Todos los análisis fueron procesados en el programa Stata versión 16.0. Se analizaron 9.184 casos, de estos, un 65% tuvieron tratamiento en un tiempo inadecuado (tiempo transcurrido entre el diagnóstico y el primer tratamiento > 60 días). La prevalencia de tratamiento en tiempo inoportuno presentó valores más elevados entre mujeres con 65 años o más (RP = 1,30; IC95%: 1,21-1,39), ninguna escolaridad (RP = 1,24; IC95%: 1,15-1,33) y estadio avanzado (RP = 1,17; IC95%: 1,13-1,21). En la mayoría de los casos analizados, hubo tratamiento en un tiempo inadecuado, con mayor prevalencia entre las mujeres con más edad, menor escolaridad y estadio clínico del tumor avanzado, evidenciando la necesidad de una ampliación del acceso a los servicios de tratamiento oncológico en el estado de Bahía, en especial para estos grupos que presentaron peor situación.

This study aimed to analyze factors associated with delay in specialized treatment after diagnosis of cervical cancer in the State of Bahia, Brazil. This was a cross-sectional hospital-based study of women treated in accredited units in the Hospital-Based Cancer Registry (HBCR) system in the State of Bahia from 2008 to 2017. A descriptive analysis and logistic regression were performed with backward stepwise modeling to estimate crude and adjusted prevalence ratios (PR), defining statistical significance as p ≤ 0.05 in Pearson's chi-square test. We analyzed 9,184 cases, and 65% had delayed treatment (time between diagnosis and first treatment > 60 days). Delayed treatment was more prevalent among women 65 years or older (PR = 1.30; 95%CI: 1.21-1.39), with no schooling (PR = 1.24; 95%CI: 1.15-1.33), and in advanced stages (PR = 1.17; 95%CI: 1.13-1.21). Most of the cases analyzed had delayed treatment, more prevalent among older women, with less schooling, and advanced tumor stages, highlighting the need to expand access to cancer treatment services in Bahia state, especially for these groups in worse conditions.

Analysis of dosimetry and clinical efficacy of intracavitary/interstitial brachytherapy in Ⅲ B cervical cancer / 中华放射肿瘤学杂志

Objective:To compare the dosimetry and efficacy of intracavitary brachytherapy (ICBT) and intracavitary/interstitial brachytherapy (IC+ ISBT) based on CT image guidance in the treatment of stage Ⅲ B cervical cancer. Methods:Clinical data of 93 patients with stage Ⅲ B cervical cancer treated in Department of Radiotherapy of Jilin Cancer Hospital from June 2014 to February 2017 were analyzed retrospectively. According to the results of Gynecological examination and pelvic MRI before brachytherapy, confirming the size of residual tumor and the degree of parauterine infiltration, all patients were divided into the ICBT and IC+ ISBT groups. The D 90%, D 100%, V 100% and D 2cm 3 of bladder and rectum were compared, and the short-term and long-term efficacy was observed between two groups. Results:The median follow-up time was 60 months. The 5-year local control rate, distant metastasis-free survival rate and overall survival rate of all patients were 83%, 71% and 68%, respectively. Compared with the ICBT group, HR-CTV D 90% in the IC+ ISBT group was all more than 85 Gy, while there was no significant difference between two groups ( P=0.188). The D 2cm 3 of bladder and rectum in the IC+ ISBT group was significantly decreased by 7 Gy and 8 Gy (both P<0.01), and the distant metastasis-free survival rate was significantly improved ( P=0.009). The 5-year local control rate in the HR-CTV volume>60 cm 3 in the IC+ ISBT group was significantly higher than that in the IC group ( P=0.029). Conclusion:For patients with Ⅲ B cervical cancer, IC+ ISBT can not only ensure target coverage, but also significantly reduce the incidence of distant metastasis and the dose of organs at risk, and significantly improve the local control rate of large tumors.

Study of three-dimensional dose distribution prediction in cervical cancer brachytherapy based on U-Net fully convolutional network / 中华放射肿瘤学杂志

Objective:Topredict the three-dimensional dose distribution of regions of interest (ROI) with brachytherapy for cervical cancer based on U-Net fully convolutional network, and evaluate the accuracy of prediction model.Methods:First, 100 cases of cervical cancer intracavity combined with interstitial implantation were selected as the entire research data set, and divided into the training set ( n=72), validation set ( n=8), and test set ( n=20). Then the U-Net was used to construct two models based on whether the uterine tandem and the implantation needles were included as the distinguishing factors. Finally, dose distribution of 20 cases in the test set were predicted using the trained model, and comparative analysis was performed. The performance of the model was jointly evaluated by , and the mean absolute deviation (MAD). Results:Compared with the model without the uterine tandem and the implantation needles, the of the rectum was increased by (16.83±1.82) cGy ( P<0.05), and the or of the other ROI were not different significantly (all P>0.05). The MAD of the high-risk clinical target volume, rectum, sigmoid, small bowel, and bladder was increased by (11.96±3.78) cGy, (11.43±0.54) cGy, (24.08±1.65) cGy, (17.04±7.17) cGy and (9.52±4.35) cGy, respectively (all P<0.05). The MAD of the intermediate-risk clinical target volume was decreased by (120.85±29.78) cGy ( P<0.05). The mean value of MAD for all ROI was decreased by (7.8±53) cGy ( P<0.05), which was closer to the actual plan. Conclusions:U-Net fully convolutional network can be used to predict three-dimensional dose distribution of patients with cervical cancer undergoing brachytherapy. Combining the uterine tube with the implantation needles as the input parameters yields more accurate predictions than a single use of the ROI structure as the input.

Application of deformable image registration in radiotherapy dose accumulation of helical tomotherapy combined with brachytherapy for cervical cancer / 中华放射肿瘤学杂志

Objective:To assess the feasibility of deformable image registration (DIR) in evaluating cumulative dose distribution of bladder and rectum of cervical cancer patients during helical tomotherapy (HT)-based intensity-modulated radiotherapy (IMRT) and high-dose-rate(HDR) brachytherapy.Methods:Clinical data of 18 patients were retrospectively analyzed. Cumulative bladder/rectum D 2cm 3 and high-risk clinical target volume (HR-CTV) D 90% parameters were calculated and compared to two direct parameter-adding methods with two registration-adding methods. Equivalent uniform dose (EUD group) and overlapping high dose (OHD group) methods were employed as parameter-adding methods. The registration-adding methods including rigid image registration (RIR group) and deformable image registration (DIR group) were adopted based on a commercial image registration software (MIM Maestro ?). The dice similarity coefficient (DSC) and mean distance to agreement (MDA) were measured to assess the accuracy of RIR and DIR. Results:In the EUD, OHD, RIR and DIR groups, the cumulative doses of bladder/rectum D 2cm 3 and HR-CTV D 90% were (80.11±3.59) Gy (EQD 2Gy), (82.23±3.46) Gy (EQD 2Gy), (80.99±6.01) Gy (EQD 2Gy) and (81.19±3.11) Gy (EQD 2Gy)( P=0.516); (72.90±3.58) Gy (EQD 2Gy), (73.83±4.28) Gy (EQD 2Gy), (72.45±6.05) Gy (EQD 2Gy) and (71.98±2.89) Gy (EQD 2Gy)( P=0.625), and (85.51±2.91) Gy (EQD 2Gy), (87.65±3.46) Gy (EQD 2Gy), (81.53±3.63) Gy (EQD 2Gy) and (85.81±3.30) Gy (EQD 2Gy)( P<0.001), respectively. The mean DSC of the bladder, rectum and HR-CTV were 0.69, 0.65 and 0.63 with RIR; and 0.85, 0.81 and 0.78 with DIR ( P<0.001), respectively. In DIR, the average MDA of bladder, rectum, and HR-CTV were 2.88, 2.48 and 2.66 mm, respectively. Conclusions:The cumulative DVH parameters among 4 groups show no significant difference in the bladder/rectum D 2cm 3/D 0.2cm 3. Since the DIR group achieves satisfactory volume matching of greater than 0.8 with DSC analysis, it can yield acceptable results for clinical application between HT IMRT and HDR BT for cervical cancer.

Application of Diffusion Weighted Imaging in Pathological Grading/Typing and Clinical Staging of 95 Cases of Cervical Adenocarcinoma / 中国医学科学院学报

Objective To investigate the correlations of diffusion weighted imaging (DWI) with pathological grading,typing and clinical staging of cervical adenocarcinoma. Methods The data of 95 patients with cervical adenocarcinoma from May 2011 to February 2018 in Cancer Hospital Chinese Academy of Medical Sciences were collected for retrospective analysis.Before treatment,conventional MRI and DWI (b=0,800 s/mm2) were performed,and the apparent diffusion coefficient (ADC) value of cervical adenocarcinoma was measured.The ADC values were compared among different pathological grades,types,and clinical stages. Results The mean ADC value was (1.00±0.25)×10-3 mm2/s in the poorly differentiation group,(1.09±0.25)×10-3 mm2/s in the moderately differentiation group,and (1.22±0.20)×10-3 mm2/s in the well differentiation group,which showed significant difference between the poorly and well differentiation groups (P=0.002).The mean ADC values were (1.04±0.24) ×10-3 mm2/s and (1.21±0.26)×10-3 mm2/s in the endocervical adenocarcinoma (usual type) group and mucinous carcinoma group,respectively,which showed significant difference (P=0.005). Conclusions The worse differentiation of cervical adenocarcinoma corresponded to the lower ADC value.The ADC value of mucinous carcinoma was higher than that of endocervical adenocarcinoma (usual type).

Prognostic analysis of patients with Ⅳ B stage hematogenous metastatic cervical squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To evaluate the prognostic factors and the value of definitive pelvic radiotherapy in patients with stage Ⅳ B hematogenous metastatic cervical squamous cell carcinoma. Methods:Clinical data of 80 patients with Ⅳ B stage squamous cell carcinoma admitted to Zhejiang Cancer Hospital from 2006 to 2016 were retrospectively analyzed. The survival analysis was conducted by Kaplan- Meier method. Prognostic factors were analyzed by Cox models. Results:The 1-, 2-and 5-year overall survival (OS) and progression-free survival (PFS) rates were 52.5%, 26.3%, 16.8% and 25%, 13.8%, 8.8%, with a median OS of 13.8 months and a median PFS of 5.6 months, respectively. The most common site of metastasis was bone (51.3%), followed by lung (36.3%) and liver (26.3%). Univariate analysis revealed that chemotherapy combined with definitive pelvic radiotherapy and ≥6 cycles of chemotherapy were positively correlated with OS and PFS, whereas ECOG performance status score of 3-4 and liver metastasis were negatively correlated with OS and PFS. In multivariate analysis, liver metastasis ( HR=2.23, 95% CI: 1.01-4.91, P=0.048) and ECOG performance status score of 3-4( HR=2.01, 95% CI: 1.03-3.91, P=0 0.040) were significantly correlated with poor OS. Subgroup multivariate analysis showed that compared with chemotherapy±palliative radiotherapy, systemic chemotherapy combined with definitive pelvic radiotherapy significantly improved OS ( HR=0.39, 95% CI: 0.18-0.84, P=0.016). Compared with double drugs combined with<4 cycles of chemotherapy, double drugs in combination with ≥4 cycles of chemotherapy significantly improved OS ( HR=0.32, 95% CI: 0.15-0.68, P=0.003). Conclusions:Patients with low ECOG performance status score or liver metastasis obtain poor prognosis. Definitive pelvic radiotherapy combined with chemotherapy can enhance clinical prognosis of patients with Ⅳ B stage hematogenous metastatic cervical squamous cell carcinoma.

Evaluation of clinical efficacy and safety of single-channel intracavitary applicator for uterine cervical cancer: 3-year long-term results of a prospective randomized phase Ⅱ clinical trial / 中华放射肿瘤学杂志

Objective:To evaluate the 3-year survival outcomes and late injury between the self-designed patent single-channel applicator, which was modified from the traditional tandem applicator and wrapped with a oval-shield alloy around the source channel and standard Fletcher-type applicator in the high-dose-rate brachytherapy for cervical cancer.Methods:Patients initially diagnosed with cervical cancer in the Affiliated Hospital of Southwest Medical University from December 2011 to April 2017 were enrolled and randomly assigned into the external beam radiotherapy (EBRT)+ single-channel intracavitary applicator group (the patent single-channel group) and EBRT+ the Fletcher applicator group. The whole pelvis irradiation was delivered with 6-MV photons via a four-field box variant or anterior and posterior parallel fields. Five to six fractions of intracavitary brachytherapy were performed at a dose of 7 Gy at point A once a week after 30 Gy (Equivalent Dose in 2 Gy at point A: 80-90 Gy). Chemotherapy was given with intravenous injection of cisplatin at a dose of 40 mg/m 2 once weekly during EBRT. Clinical efficacy and safety were evaluated after corresponding treatment. Results:In total, 150 eligible cases were assigned into the Fletcher applicator group and 149 cases into the patent single-channel group. Up to December 2020, all patients had been followed up for 3 years, and the median duration of follow-up was 61 months. In the Fletcher group, the 3-year overall survival, progression-free survival and locoregional failure-free survival was 76.3%, 78.1% and 75.4%, and 83.8%, 80.3% and 85.5% in the single-channel group, respectively. In the Fletcher group, the cumulative rate of grade 3-4 late rectal complications was 3.3% and 6.7% in the single-channel group ( P=0.122). The cumulative rate of grade 3-4 bladder complications was 1.3% in the Fletcher group and 0.7% in the single-channel group ( P=1.000). Conclusion:The self-designed patent single-channel intracavitary applicator yields equivalent long-term clinical efficacy and safety to the standard Fletcher-type three-channel applicator in the HDR brachytherapy for uterine cervical cancer.

Analysis of different prognostic effects of nadirs of neutrophils and lymphocytes during concurrent chemoradiotherapy for cervical cancer / 中华放射肿瘤学杂志

Objective:To evaluate the effects of the nadirs of neutrophils and lymphocytes during concurrent chemoradiotherapy (CCRT) on clinical prognosis of patients with cervical cancer, aiming to provide reference data for clinicians.Methods:Clinical data of FIGO (2018)Ⅰ B1-Ⅳ A cervical cancer patients treated with radical CCRT in the University of Hong Kong-Shenzhen Hospital, from January 2015 to September 2019 were analyzed. Routine blood test was performed weekly. The overall survival (OS) was calculated by Kaplan- Meier method and analyzed by log-rank test. Univariate and Multivariate prognostic analysis were performed by Cox proportional hazards model. Results:A total of 87 patients were included. The cutoff values of absolute neutrophil count nadir (ANC n) and absolute lymphocyte count nadir (ALC n) for predicting OS were determined by receiver operating characteristic curve. Compared with the ANC n of ≤2.14×10 9/L ( n=76), patients with the ANC n of > 2.14×10 9/L ( n=11) had lower 2-year OS rate (54.5% vs. 88.9%, P=0.035). Compared with ALC n of > 0.2×10 9/L ( n=49), patients with ALC n of ≤0.2×10 9/L ( n=38) obtained lower 2-year OS rate (75.3% vs. 90.8%, P=0.008). Multivariate analysis showed that ANC n (>2.14×10 9/L vs. ≤2.14×10 9/L)( HR=4.487, 95% CI: 1.404-14.344, P=0.011), ALC n (≤0.2×10 9/L vs. >0.2×10 9/L)( HR=5.814, 95% CI: 1.822-18.554, P=0.003), concurrent chemotherapy cycle (5-6 cycles vs. 0-4 cycles)( HR=0.204, 95% CI: 0.060-0.696, P=0.011) and the mean body radiation dose ( HR=1.296, 95% CI: 1.125-1.493, P<0.001) were significantly associated with OS. Patients with the ANC of > 5.19×10 9/L before CCRT were more likely to have ANC n of > 2.14×10 9/L during CCRT and those with the ALC of < 2.05×10 9/L before CCRT was more likely to have ALC n of ≤0.2×10 9/L during CCRT. Conclusions:Peripheral ANC n and ALC n during CCRT have different prognostic effects and influencing factors. Clinical prognosis of cervical cancer patients may be improved by closely monitoring routine blood parameters and optimizing treatment modality during CCRT.

The value of circulating miR-143 level in predicting early response to concurrent chemoradiotherapy in cervical cancer patients / 中华放射肿瘤学杂志

Objective:To investigate the value of serum miR-143 level combined with MRI in predicting the early response to concurrent chemoradiotherapy (CCRT) in cervical cancer.Methods:A total of 85 patients with pathologically confirmed cervical cancer underwent conventional MRI, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and dynamic contrast-enhanced MRI (DCE-MRI) before CCRT. The biopsy tissues and serum samples were collected. The differential expression of miRNA in the biopsy tissues was determined by microarray chip. The expression level of miR-143 in the serum samples was analyzed by qRT-PCR. All patients were divided into the non-residual and residual tumor groups according to post-treatment MRI. Pre-treatment clinical factors, MRI parameters and miR-143 between two groups were statistically analyzed by the univariate and multivariate analyses. The optimal thresholds and predictive performance for post-treatment incidence of residual tumors were estimated by drawing the ROC curve.Results:At one month after CCRT, there were 52 patients in the non-residual tumor group and 33 patients in the residual tumor group. In the residual tumor group, pre-treatment FIGO staging, apparent diffusion coefficient (ADC), D and V e were significantly higher (all P<0.05), whereas K trans value was significantly lower ( P<0.001) when compared to those in the non-residual tumor group. The miRNA array analysis showed that there were 16 miRNAs with differential expression levels between two groups (all P<0.05). Among them, the increase of miR-143 was the most significant in the residual tumor group. Compared with the residual tumor group, the expression level of serum miR-143 was significantly down-regulated in the non-residual tumor group ( P=0.002). Compared with the SiHa cells, the expression level of miR-143 in the SiHa-R cells was significantly up-regulated ( P<0.05). Multivariate analysis showed that only miR-143, D, K trans and V e were the independent prognostic factors. The combination of multi-parametric MRI and miR-143 exhibited the highest predictive performance (AUC=0.975), with a sensitivity of 84.8% and a specificity of 96.2%. Conclusion:The combination of multi-parametric MRI with miR-143 further improves the predictive performance for residual tumors after CCRT, which contributes to the personalized treatment of cervical cancer.

Effect of inter-fractional positional uncertainty on cumulative dose of target volume in intensity-modulated radiotherapy of cervical cancer / 中华放射肿瘤学杂志

Objective:To obtain the inter-fractional set-up errors of intensity-modulated radiotherapy (IMRT) of cervical cancer by cone-beam CT (CBCT), and to analyze the variations of the set-up errors on the cumulative dose deviation of the target volume.Methods:A total of 48 patients with cervical cancer who underwent IMRT were enrolled in this study, and the set-up errors of 696 CBCTs were obtained. The set-up errors were input into the treatment planning system, and the cumulative set-up error dose was obtained by superposing the set-up errors dose. The deviation percentage was calculated by the deviation formula and the standard planning dose.Results:The set-up errors caused the offset of isocenter distance by 0.58(0.36, 0.80) cm. Different statistical differences were noted between the cumulative set-up error dose and the standard planning dose by WilCoxon test. All the dose deviations in the target volume were reduced, and the differential dose volume histogram (DVH) appeared negatively skewed, and the peak value was declined. The DVH diagram shifted to the left with an inverse S-curve and the slope was increased. The HI deviation of the target volume from small to large were: CTV 1, CTV 2, GTV/CTV, CTV 3, CTV n, CTV all, and GTV nd; The HI deviation of the target volume were increased. Conclusions:The effect of set-up errors in IMRT of cervical cancer upon the cumulative doses of the target volume significantly differs. The cumulative dose of the target volume is reduced, and the uniformity of the target volume dose becomes worse. The uncertainty of the inter-fractional position leads to an increase or decrease in the the fractional doses of the target volume. The biological effect on tumor cells and the tumor recurrence remains to be investigated. In IMRT of cervical cancer, the CBCT position calibration is required before each treatment to ensure the dose accuracy of each structure in the target volume.

Study of occult uterine perforation in brachytherapy of cervical cancer / 中华放射肿瘤学杂志

Objective:To evaluate the difference of dosimetry between three-dimensional and two-dimensional plans based on CT images of occult perforation in brachytherapy of cervical cancer, aiming to provide clinical reference.Methods:A total of 817 patients with cervical cancer received simple intrauterine (intrauterine tandem plus vaginal colpostats) three-dimensional brachytherapy in Chongqing University Cancer Hospital from January 2019 to December 2020 were retrospectively reviewed. Among them, 16 patients had occul uterine perforation. Based on Oncentra Brachy Therapy plan system, the single prescription dose was 6Gy. Three-dimensional (3D group) and two-dimensional (2D group) plans were designed on the perforated CT images The target volume, conformal index (CI), conformal index coformity index (COIN) and organs-at-risk (OAR) D 2cm 3 parameters were used to assess the plans between two groups. Results:The incidence of pccult uterine perforation was 1.96%(16/817) during brachytherapy for cervical cancer. The volume of prescription dose curve in the 3D group was (40.74±14.98) cm 3, significantly smaller compared with (91.46±19.71) cm 3 in the 2D group ( P<0.05), whereas the volume of the high-risk clinical target area wrapped by prescription dose curve did not significantly differ between two groups ( P>0.05). The CI and COIN in the 3D group were 0.79±0.10 and 0.72±0.96, significantly higher compared with 0.38±0.09 and 0.37±0.18 in the 2D group (both P<0.05). The D 2cm 3 of bladder, rectum, sigmoid colon, small intestine in the 3D group were (306.06±77.57) cGy, (252.27±72.60) cGy, (127.25±62.84) cGy and (228.79±94.90) cGy, significantly lower than (548.03±164.21) cGy, (411.16±118.74) cGy, (227.45±94.48) cGy and (450.95±157.96) cGy in the 2D group (all P<0.05). Conclusions:Application of image guidance in brachytherapy of cervical cancer is helpful to detect occult uterine perforation. When occult uterine perforation occurs, the use of three-dimensional plan can basically meet the clinical needs, which is significantly better than the two-dimensional plan.

Impacts of treatment modes on the prognosis of Ⅰ B1-Ⅱ A patients with intermediate-risk recurrence factors / 中华放射医学与防护杂志

Objective:To analyze the prognostic factors of patients with Ⅰ B1-Ⅱ A cervical cancers after surgery and to assess the effects and adverse reactions of intensity-modulated radiotherapy(IMRT)combined with concurrent chemotherapy(CCRT). Methods:A retrospective analysis was performed based on the clinical and follow-up data of 362 patients with Ⅰ B1-Ⅱ A cervical cancers who were treated in Changzhou Second People′s Hospital from January 2009 to December 2019. Meanwhile, these patients suffered large primary tumors(LPT; tumors size: ≥4 cm), lymphatic vascular space invasion (LVSI), and deep stromal invasion(DSI; stromal infiltration depth: ≥1/2) after surgery and showed at least one intermediate-risk factor. Among these cases, 161 cases were treated with CCRT, 131 cases under-went single radiotherapy (RT), and 70 cases received unadjuvanted radiotherapy. The Kaplan-Meier method and the logrank test were adopted for univariate survival analysis, the binary logistic regression was used to analyze the recurrence risk, and Cox regression model was used for multivariate survival analysis. Results:The 3 and 5-year overall survival (OS) rates were 94.20% and 88.39%, respectively. The retrospective analysis showed that the risk factors of recurrence included tumor size ≥ 4 cm and poorly differentiated cancers( OR=3.287, 2.870, 95% CI: 1.366-7.905, 1.105-7.457, P<0.05). Compared with the treatment without adjuvant radiotherapy and RT, CCRT reduced the recurrence rate of tumors with tumor size of ≥ 4 cm, adenocarcinomas or adenosquamous carcinomas (pathological types), and poorly differentiated carcinomas( χ2=6.725-7.518, P<0.05). A multivariate analysis showed that the CCRT improved the recurrence-free survival ( HR=0.290, 95% CI: 0.128-0.659, P=0.003) and OS ( HR=0.370, 95% CI: 0.156-0.895, P=0.024). A subgroup analysis indicated that CCRT prolonged the OS of patients with tumor size ≥ 4 cm or poorly differentiated cancers compared to the patients receiving no radiotherapy or those treated with RT (χ 2=7.614, 5.964, P<0.05). Compared with the cases receiving single radiotherapy, those receiving CCRT did not suffer an increase in the incidence of hematology, radiation enteritis, and cystitis above grade 3 according to observation ( P>0.05). Conclusions:Among the intermediate-risk factors leading to the recurrence of postoperative cervical cancers, the factors of large primary tumors or poorly differentiated cancers affect the prognosis of patients.Compared with RT and the treatment without adjuvant radiotherapy, IMRT combined with concurrent chemotherapy can prolong the recurrence-free survival and overall survival of patients with large tumors or poorly differentiated cancers and adverse reactions induced are tolerable.

Uso de agrotóxicos e mortalidade por câncer em regiões de monoculturas / Use of pesticides and cancer mortality in monoculture regions

RESUMO O uso de agrotóxicos na agricultura brasileira é um problema de saúde pública, dadas as contaminações no ambiente, em alimentos e as intoxicações resultantes do uso dessas substâncias. O objetivo deste artigo é investigar a distribuição espacial das áreas plantadas de lavouras e as taxas de mortalidade de alguns tipos de câncer: mama, colo do útero e próstata. Escolheram-se quatro estados brasileiros que possuem grande produção de commodities agrícolas a serem estudadas. Trata-se de um estudo ecológico de análise espacial conduzido com dados e informações do Sistema de Informação sobre Mortalidade (SIM) do Ministério da Saúde, por meio do qual elaboraram-se taxas de mortalidade para os referidos tipos de câncer, cujos óbitos tenham ocorrido entre 1996 e 2016. Há indícios de que existe correspondência entre as áreas de maior estimativa de uso de agrotóxicos Disruptores Endócrinos e o aumento das taxas de mortalidade pelos diferentes tipos de câncer.

ABSTRACT The use of agrochemicals in Brazilian agriculture is a public health problem, given the contamination of the environment, food and the poisoning resulting from the use of these substances. The objective of this article is to investigate the spatial distribution of planted crops area and mortality rates of some types of cancer: breast, cervix and prostate. Four Brazilian states were chosen that have large production of agricultural commodities to be studied. This is an ecological study of spatial analysis conducted with data and information from the Mortality Information System (SIM) of the Ministry of Health, and mortality rates were calculated for those types of cancer whose deaths occurred between 1996 and 2016. There are indications that there is a correspondence between the areas of higher estimation of the use of agrochemical Endocrine Disruptors and the increase of mortality rates by different types of cancer.

Cáncer cérvico uterino: prevención y tratamiento / Cervical uterine cancer: prevention and treatment

RESUMEN El cáncer cérvico uterino es una alteración celular que se origina en el epitelio del cuello del útero debido a la persistencia de serotipos oncogénicos del virus del papiloma humano y que se manifiesta inicialmente a través de lesiones precancerosas de lenta y progresiva evolución. Sigue siendo la primera causa de morbimortalidad en mujeres de países en vías de desarrollo. Los datos estadísticos mundiales indican que al año se producen unos 466.000 nuevos casos, 80 % de ellos en países en vías de desarrollo, de los cuales mueren 274.000 mujeres, a pesar de ser una enfermedad prevenible. El objetivo de esta revisión es compilar información sobre su prevención y tratamiento, para poder ser utilizada con fines docentes.

ABSTRACT Cervical uterine cancer is a cellular alteration which starts in the cervix epithelium due to the persistence of human papillomavirus oncogenic serotypes and that initially manifests itself through precancerous lesions of slow and progressive evolution. It still is the leading cause of morbidity and mortality in women in developing countries. World statistical data indicates that some 466,000 new cases occur each year, 80% of them in developing countries, of which 274,000 women die, despite being a preventable disease. The objective of this review is to compile information on its prevention and treatment, in order to be used for educational purposes.

Molecular markers for the diagnosis of high-risk human papillomavirus infection and triage of human papillomavirus-positive women

ABSTRACT Infection with high-risk human papillomavirus (HPV) increases the likelihood of developing cervical cancer (CC). A plethora of cellular processes is required to produce pre-malignant lesions, which in turn may become malignant if left untreated. Those changes are induced by viral oncoproteins, which represent an ideal target to identify the viral presence, or by some particularities of the host that ultimately promote the establishment of CC. This article describes the different methods used for HPV detection and quantification, as well as the current trend of secondary screening approaches to detect premalignant lesions and CC. In addition, we analyzed validated biomarkers and those under clinical investigation for the classification (triage) of women at risk of developing CC after an initial positive HPV test and that could be used as prognostic biomarkers for CC. The use of molecular biomarkers, together with the detection of HPV DNA sequences, provides a high impact diagnostic and prognostic tool in the detection of patients at increased risk of developing CC and also may guide their clinical management. In addition, some of those biomarkers could represent pharmacological targets for the future design of therapeutic approaches to CC treatment.

Conocimientos, actitudes y prácticas sobre la prueba de citología cervical en una población rural peruana / Knowledge, attitudes and practices on cervical cytology in a Peruvian rural population

Introducción: La citología cervical constituye la principal herramienta para la detección y tratamiento del cáncer de cérvix. Algunos estudios llevados a cabo en población urbana han relacionado la realización y adherencia con los conocimientos, las actitudes y las prácticas favorables de las mujeres con respecto a esta prueba. Objetivo: evaluar los conocimientos, actitudes y prácticas con respecto a la citología cervical en mujeres pertenecientes a un grupo poblacional del ámbito rural. Material y Métodos: estudio de corte transversal-analítico en una población de aproximadamente 3148 mujeres en edad fértil, de ellas se obtuvo una muestra representativa. Se utilizó una encuesta anónima, validada, dirigida, y aplicada por personal de salud capacitado que labora en centros de salud del primer nivel de atención de los distritos de la provincia de Bolívar, La Libertad. Resultados: El 80 por ciento de las mujeres encuestadas tuvo un nivel de conocimiento alto e intermedio, el 70 por ciento una actitud favorable, mientras que el 44 por ciento reportó prácticas correctas en relación con la prueba de citología cervical. El nivel de conocimiento alto e intermedio estuvo asociado a la edad mayor de 30 años (p:0.02), estado civil casada (p:0.05), el mayor grado de instrucción (p:0.00) y el uso de métodos anticonceptivos (p:0.01); no se encontró relación con la edad de inicio de relaciones sexuales (p:0.98). Conclusiones: Existe un alto nivel de conocimientos, actitudes y prácticas correctas hacia la citología cervical en la población rural de la provincia de Bolívar, pero una baja adherencia hacia la misma(AU)

Introduction: Cervical cytology is the main tool for the detection and treatment of cervical cancer. Some studies carried out in the urban population have associated the realization and adherence with knowledge, attitudes and favorable practices of women with respect to this test. Objective: The aim of this study was to determine the level of knowledge, attitudes and practices towards cervical cytology in women of childbearing age in a rural Peruvian province. Material and Methods: A cross-sectional analytical study was conducted in a population of approximately 3148 women of childbearing age, a representative sample was obtained. An anonymous, validated, directed survey was used; it was applied by trained health personnel working in health centers of the primary care level in the districts of the province of Bolívar, La Libertad. Results: A total of 400 surveys were carried out. The results showed that 80 percent of the women surveyed had high and intermediate levels of knowledge, 70 percent had a favorable attitude, while 44 percent reported correct practices related to the cervical cytology test. The high and intermediate levels of knowledge were associated with age over 30 years (p: 0.02), married marital status (p: 0.05), the highest level of instruction (p: 0.00) and the use of contraceptive methods (p: 0.01); no relationship was found with the age of onset of sexual intercourse (p: 0.98). Conclusions: There is a high level of knowledge, attitudes and correct practices towards cervical cytology in the rural population of the province of Bolívar, but a low adherence to it(AU)

Study of the feasibility of needle path optimization in 3D brachytherapy for cervical cancer / 中华放射肿瘤学杂志

Objective To compare the dosimetric differences between free-hand method and virtually optimized method for implanting needles in intracavitary and interstitial combined brachytherapy (IC/IS BT) of cervical cancer,and to explore the improvement space of the existing interstitial brahcytherapy plan.Methods High-dose-rate cervical cancer IC/IS BT plans (short for Treatment-Plan) of 18 cases were retrospectively analyzed.For each treatment plan,Nucletron Oncentra 3D brachytherapy planning system was utilized to redesign the virtually optimized insertion method IC/IS BT plan (short for Optimized-Plan).Dose volume histogram was adopted to evaluate the dose distribution in high-risk clinical target areas and exposure dose to organ at risk (OAR).The plan execution efficiency between two plans was also assessed.Results Comparing these two plans,the differences in conformity and uniformity of dose distribution of the target area were statistically significant (P=0.000,0.008).The differences of D0.01 cm3,D1 cm3,D2 cm3 and D5 cm3 in bladder,rectum,sigmoid and small bowel were all statistically significant (all P＜0.05).Optimized-Plan could reduce the D2 cm3 of bladder,rectum,sigmoid and small bowel by 60.41,36.43,27.53 and 12.43 cGy,respectively.The execution time for the Treatment-Plan and Optimized-Plan were (857.92±243.39) s and (804.53±239.13) s with statistical significance (P＜0.001).Conclusions Compared with the free-hand method,virtually optimized method yields more conformable coverage of the target area and more uniform dose distribution.At the same time,the doses of each OAR are reduced to different degrees and the execution time of the plan is also shortened.