Análisis de la inmunidad de las mujeres infectadas por el virus del papiloma humano y su relación con la lesión intraepitelial cervical / Immunity analysis in women infected with human papillomavirus and its link with cervical intraepithelial lesion (IMVIR study)

Introducción: El objetivo principal es estudiar los marcadores de NK memoria presentes en sangre periférica en pacientes con lesiones cervicales intraepiteliales de alto grado CIN2/3 frente a mujeres sin lesiones o con lesiones de bajo grado. Los objetivos secundarios son estudiar la relación entre el perfil de las células NK memoria y la infección o no por VPH, así como la persistencia viral en las mujeres infectadas por VPH. Material y métodos: Se trata de un estudio observacional prospectivo de una cohorte de mujeres reclutadas desde el año 2019, durante un periodo de 2años, en la unidad del tracto genital inferior en las consultas de ginecología general del Instituto de Salud de la Mujer del Hospital Clínico San Carlos. Los grupos de pacientes incluidos en el estudio son el grupo de estudio: mujeres con infección por VPH y con lesión cervical de alto grado (CIN2+); el grupo control1: mujeres con infección por el VPH sin lesión cervical de alto grado, y el grupo control2: mujeres sin infección por el VPH y sin lesión. Resultados: Durante el estudio se han reclutado 115 pacientes. Nos encontramos con un mayor número de NK «memoria» en pacientes infectadas, tanto en el grupo control1 como en el grupo de estudio, en comparación con el grupo control2. Además, cuando se analizan las pacientes no fumadoras, la expresión de NKp30 es significativamente menor en el grupo control1. Conclusiones: Los resultados ponen de manifiesto una probable menor capacidad para desarrollar funciones adaptativas por parte de las células NK en estas pacientes fumadoras frente a las no fumadoras. Un mejor conocimiento de la biología de las células NK y su papel en la infección por el VPH podría permitir el desarrollo de estrategias para manipular su funcionamiento (inmunoterapias) con un propósito pronóstico y terapéutico.(AU)

Introduction: The main objective is to study the NK markers present in circulating blood in patients with high grade intraepithelial cervical lesions compared with women without lesions or low grade lesions. The secondary objectives of the study are to understand the relationship between the NK memory like cells and the infection with HPV, as well as the persistence of the infection. Methods and materials: It is an observational prospective study that studies women from 2019 for 2years seen in ginecology rooms in Hospital Clínico San Carlos. The group of patients studied are: women with infection by HPV and high grade lesions, women with infection by HPV but no lesion or low grade lesion and women without lesion or infection. Results: We have recruited 115 patients. We have found more memory like NK cells in patients infected by HPV. And when we analyze the non-smoking patients, the expression of NKp30 is lower in patients infected without lesion. Conclusions: The results show that there could be less capacity to generate an adaptative function by NK in smoking patients than in non-smoking. A better knowledge of the NK cells biology and its role in the infection by HPV could allow us to manipulate with a therapeutic and prognostic end.(AU)

The impact of boost radiation therapy after hysterectomy on cervical cancer patients with close or positive resection margins

Purpose We investigated the effect of boost radiation therapy (RT) in addition to whole pelvis RT (WPRT) on treatment outcome and safety of cervical cancer patients following hysterectomy with close/positive resection margins (RM). Methods We retrospectively analyzed 51 patients with cervical cancer who received WPRT with or without boost-RT as adjuvant treatment between July 2006 and June 2022. Twenty patients (39.2%) were treated with WPRT-alone, and 31 (60.8%) received boost-RT after WPRT using brachytherapy or intensity-modulated RT. Results The median follow-up period was 41 months. According to RT modality, the 4-year local control (LC) and locoregional control (LRC) rates of patients treated with WPRT-alone were 61% and 61%, respectively, whereas those in LC and LRC rates in patients who underwent WPRT with boost-RT were 93.2% and 75.3%, with p-values equal to 0.005 and 0.090, respectively. Seven patients (35.0%) had local recurrence in the WPRT-treated group compared to only two out of the 31 patients (6.5%) in the WPRT with boost-RT-treated counterparts (p = 0.025). Boost-RT was a significantly good prognostic factor for LC (p = 0.013) and LRC (p = 0.013). Boost-RT did not result in statistically-significant improvements in progression-free survival or overall survival. The acute and late toxicity rates were not significantly different between groups. Conclusion Boost RT following WPRT is a safe and effective treatment strategy to improve LC without increasing toxicity in patients with cervical cancer with close/positive RM after hysterectomy (AU)

Linfoma difuso de célulasB grandes primario de cérvix. A propósito de un caso / Primary diffuse large Bcell lymphoma of the cervix: Clinical case

Introducción: La afectación primaria del tracto genital femenino por linfoma no Hodgkin es muy poco frecuente, por lo que no existe un consenso sobre el tratamiento, y por ello presentamos este caso clínico y el tratamiento realizado, así como el pronóstico de nuestra paciente. Hallazgos clínicos: La paciente presentada es una mujer de 72años que consulta por hemorragia vaginal. Diagnóstico Se diagnostica de linfoma no Hodgkin extranodal primario de cérvix de inmunofenotipoB de alto grado citológico y elevado índice proliferativo. Intervenciones terapéuticas y resultados: El tratamiento de elección fue únicamente quimioterápico. Esta paciente ha presentado una supervivencia libre de enfermedad de 5años. Actualmente se encuentra en seguimiento mediante la realización de controles analíticos anuales. Conclusión: Los síntomas de este tipo de tumor son altamente inespecíficos y la citología es frecuentemente negativa, por lo que es necesario recurrir a la biopsia. La inmunohistoquímica resulta fundamental tanto para el diagnóstico como para el pronóstico. Existen múltiples técnicas de imagen empleadas tanto para estudio de extensión como para seguimiento, destacando el papel del FDG-PET. Actualmente parece que el tratamiento más recomendable es la pauta quimioterápica R-CHOP seguida de radioterapia. El pronóstico en general es bueno, con hasta un 80% de supervivencia a los 5años.(AU)

Introduction: Primary involvement of the female genital tract by non-Hodgkin lymphoma is very rare, so there is no consensus on treatment, and for this reason we present this clinical case and the treatment performed, as well as the prognosis of our patient. Clinical findings: The patient presented is a 72-year-old woman who consulted for vaginal bleeding. Diagnosis: Primary extranodal non-Hodgkin lymphoma of the cervix with immunophenotypeB of high cytological grade and high proliferative index was diagnosed. Therapeutic interventions and results: The treatment of choice was chemotherapy only. This patient has presented a disease-free survival of 5years. It is currently being monitored by carrying out annual analytical controls. Conclusion: The symptoms of this type of tumor are highly non-specific, as well as cytology is frequently negative, which is why it is necessary to resort to biopsy. Immunohistochemistry is essential for both diagnosis and prognosis. There are multiple imaging techniques used for both extension study and follow-up, highlighting the role of FDG-PET. It currently seems that the most recommendable treatment is the R-CHOP chemotherapy regimen followed by radiotherapy.The prognosis is generally good, with up to 80% survival at 5years.(AU)

Cervical carcinoma induces NLRP3 inflammasome activation and IL-1ß release in human peripheral blood monocytes affecting patients’ overall survival

Purpose Our group previously demonstrated that genetic variants in inflammasome genes contribute to protection against the establishment of human papilloma virus (HPV)-associated cervical carcinoma (CC). The objective of this study was to better understand the contribution of inflammasome and its cytokines in the CC microenvironment. Methods The inflammasome activation was analyzed in CC tumoral cell lines and healthy donors (HD)’ monocytes in co-culture. In vitro results were then compared to CC patients’ public databases. Results CC cells did not produce IL-1ß or IL-18 themselves, however, when in co-culture with HD monocytes, induced IL-1ß release in those leucocytes. Inflammasome activation appears to be partially dependent on the NLRP3 receptor. Public data analysis revealed that IL1B expression is increased in the CC compared to normal uterine cervix, and that patients with high IL1B expression had a shorter overall survival. Conclusion CC microenvironment can activate the inflammasome and IL-1ß release in surrounding monocytes, which could be detrimental for CC prognosis (AU)

Optimal cisplatin cycles in locally advanced cervical carcinoma patients treated with concurrent chemoradiotherapy

Purpose To analyze the effect of cisplatin cycles on the clinical outcomes of patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy (CCRT). Methods This study included 749 patients with LACC treated with CCRT between January 2011 and December 2015. A receiver operating characteristic (ROC) curve was used to analyze the optimal cut-off of cisplatin cycles in predicting clinical outcomes. Clinicopathological features of the patients were compared using the Chi-square test. Prognosis was assessed using log-rank tests and Cox proportional hazard models. Toxicities were compared among different cisplatin cycle groups. Results Based on the ROC curve, the optimal cut-off of the cisplatin cycles was 4.5 (sensitivity, 64.3%; specificity, 54.3%). The 3-year overall, disease-free, loco-regional relapse-free, and distant metastasis-free survival for patients with low-cycles (cisplatin cycles < 5) and high-cycles (≥ 5) were 81.5% and 89.0% (P < 0.001), 73.4% and 80.1% (P = 0.024), 83.0% and 90.8% (P = 0.005), and 84.9% and 86.8% (P = 0.271), respectively. In multivariate analysis, cisplatin cycles were an independent prognostic factor for overall survival. In the subgroup analysis of high-cycle patients, patients who received over five cisplatin cycles had similar overall, disease-free, loco-regional relapse-free, and distant metastasis-free survival to patients treated with five cycles. Acute and late toxicities were not different between the two groups. Conclusion Cisplatin cycles were associated with overall, disease-free, and loco-regional relapse-free survival in LACC patients who received CCRT. Five cycles appeared to be the optimal number of cisplatin cycles during CCRT (AU)

3D Laparoscopic Ureterolysis for Retroperitoneal Fibrosis Secondary to Radical Hysterectomy and Radiation Treatment for Cervical Cancer: Results from the Oncological Institute, Cluj Napoca

Background: Ureterolysis represents the surgical treatment for retroperitoneal fibrosis. The aim of the study was to review the outcomes of patients who had undergone radical hysterectomy and radiotherapy for cervical cancer that later developed retroperitoneal fibrosis, for whom 3D laparoscopic ureterolysis was performed in our department and to review current published studies. Methods: We present a series of cases consisting of 6 patients with secondary retroperitoneal fibrosis. In all cases, the intervention was performed by the same surgeon from the Oncological Institute “Prof. Dr. Ion Chiricuț㔠Cluj-Napoca, Romania. We carried out a literature review, searching in the PubMed and MEDLINE studies published between 2000 and 2021 relevant to the matter and a total of 12 papers were selected. We reviewed the functional outcomes of patients that underwent minimally invasive ureterolysis. Results: 3D laparoscopic ureterolysis was performed in 6 patients. Mean operative time was 166 minutes and mean blood loss was 203 mL. No surgery required conversion. Five patients showed good functional results after ureteral stent removal. In one case, the patient developed acute pyelonephritis and the ureteral stents were kept. Conclusions: Laparoscopic ureterolysis for retroperitoneal fibrosis secondary to operated and radiation-treated cervical cancer represents one of the most complex and challenging surgeries in the urological field (AU)

Manejo conservador con radioterapia e inmunoquimioterapia en el linfoma difuso de células B grandes primario de cuello uterino: Diagnóstico y tratamiento de una entidad rara / Conservative management with radiotherapy and immunochemotherapy in primary diffuse large B-cell lymphoma of the cervix: Diagnosis and treatment of a rare entity

Introducción: El linfoma maligno primario de cuello uterino es una enfermedad muy rara, que representa solo el 0,008% de todos los tumores de cérvix y el 2% de todos los linfomas extraganglionares femeninos.Principales síntomas o hallazgos clínicos: Se presenta el caso de una mujer de 66 años, de los Andes peruanos, con tiempo de enfermedad de 4 meses caracterizado por ginecorragia, con evidencia de cérvix tumoral de 5cm. Se realizó inmunohistoquímica a la biopsia de cérvix para diferencia linfoma del carcinoma epidermoide.Diagnóstico principal: Linfoma difuso de células B grandes primario de cuello uterino con estadificación Ann Arbor IE IPI de bajo riesgo.Intervenciones terapéuticas y resultados: Fue manejada con inmunoquimioterapia (rituximab, ciclofosfamida, adriamicina, vincristina y prednisona), seguida de radioterapia externa consolidativa a dosis de 3.000 cGy en 15 sesiones con técnica especial IMRT. El control de la enfermedad resultó satisfactorio y no presentó complicaciones por la irradiación.Conclusión: El linfoma difuso de células B grandes primario de cuello uterino es muy raro, por lo que, en un caso de lesión primaria del estroma del cérvix, debe tenerse en cuenta la sospecha de linfoma.(AU)

Introduction: Primary malignant cervical lymphoma is a very rare disease, which represents only 0.008% of all cervical tumors and 2% of all female extranodal lymphomas. Main symptoms and/or clinical findings: The case of a 66-year-old woman from the Peruvian Andes is presented, with a disease period of 4 months characterized by gynaecorrhagia, with evidence of a 5cm tumor cervix. Immunohistochemistry was performed on the biopsy of cervix to differentiate lymphoma from squamous cell carcinoma. Primary diagnosis: Primary diffuse large B-cell lymphoma of the cervix with Ann Arbor IE IPI low-risk staging. Therapeutic interventions and results: She being managed with immunochemotherapy (rituximab, cyclophosphamide, adriamycin, vincristine and prednisone), followed by consolidative external radiotherapy at a dose of 3,000cGy in 15 sessions with a special IMRT technique. Resulting in satisfactory disease control and no complications from irradiation.Conclusion: Primary diffuse large B-cell lymphoma of the cervix is very rare, therefore, in a case of primary stromal lesion of the cervix, suspicion of lymphoma should be taken into account.(AU)

Effects of CpG sites methylation modification of HPV16 integration essential gene on the proliferation of cervical cancer cells

Purpose The mechanism of methylation of HPV CpG sites in the occurrence and prognosis of cervical carcinogenesis remains unclear. We investigated the effects of demethylation of the CpG sites of E2 and E6, essential genes of HPV16 integration, on cervical cancer cell expression, integration, and proliferation. Materials and Methods HPV16-positive (Caski) cells were treated with different concentrations of the demethylation compound 5-aza-dc (0, 5, 10, 20 μmol/l) in vitro. After the intervention, the methylation statuses of HPV16 E2 and E6 were detected by TBS, the expression levels of E2 and E6 mRNA and protein were detected by real-time PCR and western blot, cell proliferation activity was detected by CCK8, and cell cycle and apoptosis were determined by FCM. GraphPad Prism version 8.4.2 and R version 4.2.3 were used for relevant data analyses. Results The methylation levels of HPV16 E2 and E6 CpG sites decreased gradually with increasing 5-aza-dc intervention concentrations. With decreasing E2 and E6 methylation rates, E2 expression increased, the E2/E6 ratio increased, E6 expression decreased, and the growth inhibition rate of Caski cells increased. E2 and E6 expression were negatively and positively correlated with their degrees of methylation respectively, while the E2/E6 mRNA to protein ratio was negatively correlated with the methylation degrees of E2 and E6. Conclusion Demethylation can be used as a prospective treatment to affect HPV expression and persistent infection, providing a new theoretical basis for the clinical treatment of viral infections (AU)

Cost effectiveness of cervical cancer prevention strategies in Indonesia

Background: The development of several HPV-related control techniques for the prevention of cervical cancer followed the identification of a link between high-risk human papillomavirus (HPV) infection and the occurrence of cervical cancer. Objective: The objective of the current study was to determine how cost-effective the different cervical cancer screening programs and HPV vaccinations in Indonesia. Methods: The lifetime costs and effects of vaccination among adolescent girls or screening with either the VIA, Papanicolaou, or HPV DNA test at various time intervals in a hypothetical cohort of 30-65 years-old women were estimated using a Markov model based on a societal perspective. Results: Based on statistics on transition probabilities, efficacy of HPV vaccination, and diagnostic accuracy of screening procedures. The findings of this study, specifically the cost-effectiveness of preventing cervical cancer with vaccination, revealed that each woman’s vaccination cost was $16. The amount of disease-adjusted life years (DALYs) that may be saved was $213, and the averted cost per death was $1.438. Conclusion: Early cervical cancer screening using the IVA test method has a net cost of $576 for years of quality-adjusted life saved and costs $18 each examination for each woman, $1,532 for each preventable death. When the group of teenage girls who received the HPV, vaccine reaches the age of 30, the VIA screening frequency should be decided depending on the cohort’s overall HPV vaccination coverage. (AU)

LncRNA HOTAIR enhances RCC2 to accelerate cervical cancer progression by sponging miR-331-3p

Purpose Long noncoding RNAs (lncRNAs) have been gradually regarded as influential indicators of various cancers. The present study aimed to identify the effects of lncRNA HOTAIR on cervical cancer progression. Methods RNA and protein expressions were quantified by RT-qPCR and western blot assays. Fluorescence in situ hybridization (FISH) assay was carried out to examine the intracellular location of HOTAIR. Cancer cell viability and mobility were detected by CCK-8, colony formation, transwell and wound healing assays. Binding relationships between miR-331-3p and HOTAIR/RCC2 were validated by luciferase reporter assay. Results RT-qPCR assays showed that HOTAIR levels were notably upregulated in cervical cancer tissues and cell lines. Furthermore, a fluorescence in situ hybridization (FISH) assay suggested that HOTAIR was mostly located in the cytoplasm of cancer cells, indicating a sponging function. CCK-8, colony formation, Transwell and wound-healing assays indicated that knockdown of HOTAIR in HeLa and SiHa cells significantly reduced cell growth, migration and invasion. Subsequently, miR-331-3p was proven to be the target molecule of HOTAIR. In addition, results from Pearson's correlation analysis indicated negative correlation between HOTAIR and miR-331-3p in cervical cancer tissues. HOTAIR negatively modulated miR-331-3p expression. Ultimately, the target gene of miR-331-3p was verified to be RCC2, and miR-331-3p negatively modulated RCC2 expression. In addition, analysis on clinical cervical cancer tissues confirmed the negative correlation between miR-331-3p and RCC2. HOTAIR and RCC2 showed oncogenic functions in HeLa and SiHa cells, while miR-331-3p exerted the reverse effect. Conclusions HOTAIR plays a carcinogenic role in cervical cancer by targeting the miR-331-3p/RCC2 axis (AU)

Immune infiltration could predict the efficacy of short-term radiotherapy in patients with cervical cancer

Radiotherapy is the main treatment for cervical cancer. It is usually applied alone or in combination with surgery and/or chemotherapy. To explore the association between immune microenvironment of cervical cancer and radiotherapy response, we collected 20 paired cervical cancer tumor samples before and after radiotherapy and partial clinical information. With paired-end RNA-seq, we quantified the immune infiltration and tumor purity of these samples, and obtained 6350 differentially expressed genes before and after radiotherapy. With the help of R language, the function enrichment analysis and 22 immune cells infiltration analysis were carried out. Moreover, we built a random forest model based on the immune microenvironment to predict the short-term efficacy of radiotherapy. We found that the effect of radiotherapy on the immune microenvironment of stage III and IV cervical cancer patients was weaker than that of stage I and II cervical cancer patients. Radiotherapy can significantly reduce the tumor purity and increase immune infiltration. The proportions of the immune infiltrating cells are predictive of the radiotherapy efficacy. In addition, the local mucositis caused by radiotherapy can improve the curative effect of radiotherapy (AU)

Estudio piloto comparativo del test VPH con genotipado parcial en primera línea frente a otras estrategias de cribado poblacional del cáncer de cérvix. Estudio CRYGEN 16/18 / Comparative pilot study about HPV test with partial genotyping in primary screening versus other strategies for cervical cancer population screening, CRYGEN 16/18 study

Introducción: La detección precoz del cáncer de cérvix requiere la implementación de programas de cribado del virus del papiloma humano (VPH). Sin embargo, existen discrepancias en la optimización de esas estrategias. Se evalúa el rendimiento de 10 protocolos basados en técnicas moleculares, citológicas o combinadas en cribado primario. Material y métodos: Se diseña un estudio ciego, prospectivo e intervencionista en 1.977 mujeres de 35 años. La determinación molecular se realizó por la plataforma Cobas 4800HPV. Los análisis citológicos se realizaron en las mismas muestras sin conocimiento del resultado molecular. Todas las mujeres en las que se detectaba VPH-16/VPH-18 o presentaban alteración citológica y detección de otros genotipos de alto riesgo (VPHar) eran derivadas a colposcopia. Resultados: El ensayo molecular detectó presencia de VPHar en el 12,5% de las mujeres, mientras solo el 8,1% de las citologías fueron patológicas. El 19,5% de las pacientes derivadas a colposcopia revelaron lesiones de alto grado, estando VPH-16 presente en el 65,3% de ellas. En 6 de esas ocasiones (VPH-16 siempre presente) la citología había sido informada como normal. El seguimiento al año de las mujeres con citología normal y detección de VPHar identificó una lesión HSIL/CIN2+(asociada a VPH-33). En el estudio comparativo con otras estrategias el protocolo denominado CRYGEN 16/18 rindió el mejor equilibrio de sensibilidad y especificidad con la menor derivación a colposcopia. Conclusiones. La realización de detección molecular de VPH con genotipado parcial en primera línea, al menos VPH-16, con derivación directa a colposcopia, aumenta la tasa de detección de lesiones HSIL/CIN2+.(AU)

Introduction: The early detection of cervical cancer requires the implementation of molecular screening programs for human papillomavirus (HPV). However, there are discrepancies in the optimization of screening protocols. The performance of 10 primary screening strategies based on molecular, cytological or combined techniques is now evaluated. Material and methods: A blind, prospective, and interventional study was designed in 1977 35-year-old women. The molecular determination was carried out by the Cobas 4800 HPV platform. Cytological analysis was performed on the same samples without knowledge of the result of the molecular assay. All women in whom HPV-16/HPV-18 was detected or presented cytological alteration together with detection of other high-risk genotypes (HPVhr) were referred to colposcopy. Results: The molecular assay detected the presence of HPVhr genotypes in 12.5% of the women, while only 8.1% of the cytologies were pathological. Among the patients referred to colposcopy, in 19.5% high-grade lesions were observed, being HPV-16 present in 65.3% of them. In six of these high-grade lesions (associated with HPV-16 in all cases), cytology was reported as normal. The follow-up one year later, of women with normal cytology and HPVhr detection a HSIL/CIN2+ lesion was detected (associated to HPV-33). In the comparative study with other strategies, the protocol called CRYGEN 16/18 yielded the best balance of sensitivity and specificity with the least referral to colposcopy. Conclusions: Performing molecular detection of HPVhr with partial first-line genotyping of at least HPV-16, with direct referral to colposcopy, increases the detection rate of HSIL/CIN2+ lesions.(AU)

Factores de riesgo y estilos de vida en adolescentes asociados al cáncer en la adultez: una revisión de alcance / Fatores de risco e estilos de vida em adolescentes associados ao câncer na idadeadulta: uma revisão de escopo / Risk factors and lifestyles in adolescents associated with cancer in adulthood: a scoping review

Objective: To identify scientific evidence related to risk factors and lifestyles in adolescentsassociated with the occurrence of lung, cervical, gastrointestinal, skin and breast cancer in adulthood. Methodology: Scope review based on the methodology of the Joanna Briggs Institute (JBI),four databases were explored, and the selected articles were analyzed, extracted and synthesized.Results: 33 articles were included, the risk factors identified were family history, sex, tobacco, alcohol, overweight, underweight, sun exposure, human papillomavirus (HPV) infection, lack ofknowledge about self-care measures, low consumption of fruits and vegetables, consumption of redmeat and fats, low socioeconomic status, low level of schooling and sedentary lifestyle: physicalactivity, condom use, monitoring and screening of their health status, human papillomavirus (HPV)vaccination, healthy eating and sun protection. Conclusion: The risk factors found in the scope review are numerous, according to each type of cancer, there are modifiable factors that can be putinto practice from adolescence as lifestyles in the individual, family and school sense.(AU)

Objetivo: Identificar la evidencia científica relacionada con los factores de riesgo y losestilos de vida en adolescentes asociados a la ocurrencia de cáncer pulmonar, cervicouterino, gastrointestinal, de piel y de mama en la adultez. Metodología: Revisión de alcance basada en la metodología del Joanna Briggs Institute (JBI), se exploraron cuatro bases de datos, a los artículos seleccionados se les realizó análisis, extracción y síntesis de datos. Resultados: Se incluyeron 33 artículos,los factores de riesgo identificados fueron antecedentes familiares, sexo, tabaco, alcohol, sobrepeso, bajo peso, exposición al sol, infección por virus del papiloma humano (VPH), desconocimientosobre medidas de autocuidado, bajo consumo de frutas y verduras, consumo de carnes rojas y degrasas, bajo nivel socioeconómico, bajo nivel de escolaridad y sedentarismo; y, como estilos de vida:actividad física, uso del condón, seguimiento y detección de su situación de salud, vacuna contra elvirus del papiloma humano (VPH), alimentación saludable y protección solar. Conclusión: Los factores de riesgos encontrados en la revisión de alcance son numerosos, según cada tipo de cáncer,existen factores modificables que desde la adolescencia se pueden poner en práctica como estilos devida en sentido individual, familiar y escolar. (AU)

Objectivo: Identificar provas científicas relacionadas com factores de risco e estilos de vidaem adolescentes associados com a ocorrência de cancro do pulmão, cervical, gastrointestinal, dapele e da mama na idade adulta. Metodologia: Revisão do âmbito com base na metodologia doInstituto Joanna Briggs (JBI), foram exploradas quatro bases de dados e foram analisados, extraídose sintetizados artigos seleccionados. Resultados: 33 artigos foram incluídos, os factores de risco identificados foram história familiar, sexo, tabaco, álcool, excesso de peso, baixo peso, exposição solar,infecção por papilomavírus humano (HPV), falta de conhecimento sobre medidas de autocuidado,baixo consumo de frutas e vegetais, consumo de carne vermelha e gordura, baixo estatuto socioeconómico, baixo nível de educação e sedentarismo; e, como estilos de vida: actividade física, utilizaçãode preservativos, monitorização e rastreio do seu estado de saúde, vacinação contra o papilomavírus humano (HPV), alimentação saudável e protecção solar. Conclusão: Os factores de risco encontrados na revisão do âmbito são numerosos, dependendo de cada tipo de cancro, e há factores modificáveis que podem ser postos em prática a partir da adolescência como estilos de vida individuais, familiares e escolares.(AU)

STAT3 inhibitor BBI608 reduces patient-specific primary cell viability of cervical and endometrial cancer at a clinical-relevant concentration

Aberrant activation of STAT3 signal pathway promotes tumor progression in many solid tumor types, including cervical cancer and endometrial cancer. BBI608, the STAT3 inhibitor had been reported in previous studies for restraining cancer stem cells. However, whether BBI608 is available for inhibiting the proliferation of cervical cancer or endometrial cancer remains poorly understood. This study investigated the anti-tumor effect and molecular mechanism of BBI608 on the patient-specific primary cells (PSPC) generated from cervical and endometrial cancer in vitro. Methods PSPCs were obtained from four patients via biopsy. The cell viability was analyzed by the CCK8 assay. The PSPCs were treated with various concentrations of BBI608 or/and paclitaxel; and then, western blot was applied to investigate the expression of phosphorylated STAT3 (pSTAT3). Results The PSPCs cell viability was reduced after treated with BBI608 at a lower concentration. Western blot results showed a reduction trend of pSTAT3 after PSPCs treated with BBI608. Our results demonstrated that BBI608 at the certain concentrations worked well in reducing the cell viability of PSPC from the patients who suffered from cervical cancer and endometrial cancer. Conclusions In this study, the patient-specific primary cell (PSPC) was used as the pre-clinical model for investigating the efficiency of BBI608 in reducing cancer cells viability. BBI608, at a clinical-relevant concentration, had valid efficiency in PSPCs from the patients. The dose of drugs treatment and the measured results were more valuable for further guiding clinical trials (AU)

Breast, Cervical, and Lung Cancer: A comparison of Real Healthcare Costs and INA-CBGs Rates in the Era of National Health Insurance

Background: In Indonesia, the cost of cancer treatment has been determined by the Indonesian Case Base Groups (INA-CBGs) based on a code called the INA-CBG’s rates. However, a fair claim should be based on the severity of the disease and the class of treatment in the hospital, not on the rates of code. In fact, the real cost of therapy for cancer is influenced by several factors including stage, comorbidity, and severity (INA-CBGs coding, type of hospital, hospital class, treatment grade, side effects, and length of stay), so in many cases, there are reported differences between the real costs and the INA-CBGs rates charged to patients. Objective: This study aims to investigate the difference between real treatment costs and INA-CBG’s rates for cases of lung cancer, cervical cancer, and breast cancer at a cancer center hospital in Indonesia. Methods: This work uses an observational study, and the data were taken retrospectively from hospital financial data and patient medical records. The data were then analyzed using a one-sample t-test to determine the difference between real costs and INA-CBGs costs. Results: The results showed that there was no significant difference between real costs and INA-CBG’s cost on stage II lung cancer treatment in grade 2 with a sig. value of 0.683; code C-4-13-II in grade 3 with a sig. value of 0.151; and code C-4-13-III in grade 3 with a sig. value of 0.650; where the significance level (t alpha) is more than 0.05. Furthermore, the treatment costs for cervical cancer with codes C-4- 13-I and C-4-13-II in grade 1 had sig. values of 0.155 and 0.720 respectively. Lastly, the treatment cost for breast cancer patients with codes C-4-12-II in grade 3 had a sig. value of 0.145 and code C-4-13-II in grade 3 showed a sig. value of 0.091. (AU)

Multiparametric immune profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: an exploratory study of the CLAP trial

Purpose Checkpoint immunotherapy is a promising treatment option for advanced cervical cancer. To aid in selecting patients for this treatment, we identified potential predictors of the response to anti-PD-1 combination therapy. Methods We simultaneously characterized CD8+, FoxP3+, PD-L1+, CD68+, CD31+, PANCK+, and PANCK−PD-L1+ cells at the invasive margin (IM) of tumor by multispectral imaging of tissue sections from 37 patients with advanced cervical cancer in our previous trial cohort. The densities of each cell and cell-to-cell topography were compared between the responder and non-responder groups and evaluated for their predictive value in clinical response and survival. Results CD8+ T cells, PD-L1+ cells, and PANCK−PD-L1+ immune cells showed higher densities at the IM in the responders than in the non-responders (P = 0.022, 0.0094, and 0.049, respectively). A higher density of CD8+ T cells at the IM was related to prolonged progression-free survival (PFS; P = 0.031). A higher ratio of CD68+/CD8+ cells was found in the non-responder group (P = 0.003) and related to poor PFS (P = 0.016). A higher density of PANCK−PD-L1+ immune cells within 20, 30, and 45 µm of PANCK+ tumor cells was correlated with better clinical response (P = 0.017, 0.017, and 0.02, respectively). Conclusions Multiparametric immune profiling of CD8+ T cells, PD-L1+ cells, CD68+ macrophages and PANCK−PD-L1+ immune cells at the invasive margin may help identify patients with cervical cancer who may benefit from anti-PD-1 combination therapy. (AU)

Study on the mechanism of let-7a-5p in regulating the proliferation in cervical cancer cells

PurposeTo explore the regulatory effect of let-7a-5p/TGFBR1/Smad3 on the proliferation activity of cervical cancer cells.MethodsThe difference in let-7a-5p expression between normal people and patients with cervical cancer was detected by miREIA assay. The differences of let-7a-5p expression between cervical cancer cell line C33a and adjacent normal epithelial cell line HUCEC were determined by qRT-PCR.ResultsmiREIA result showed that let-7a-5p concentrations were 178.5 ± 24.3 μg/L in healthy individuals and 106.1 ± 14.8 μg/L in cervical cancer patients (P = 0.0002). qRT-PCR showed that let-7a-5p in cervical cancer tissue (0.57 ± 0.03) was lower than that in adjacent normal tissue (0.84 ± 0.04, P = 0.0107). Compared with normal cervical epithelial cells (HUCEC), the expression of let-7a-5p was lower in cervical cancer cells (C33a, Hela, P = 0.0001). The results of CCK-8 and EDU detection showed that activation of let-7a-5p inhibited the proliferation of C33a (P = 0.00130, P << 0.0001) and Hela (P = 0.00254, P = 0.0066) cells. According to the analysis using Starbase V2.0 online database, let-7a-5p could target TGFβR1 in cervical cancer cell lines, and the let-7a-5p mimic reduces the mRNA expression level of TGFβR1 in cervical cancer cell C33a (P = 0.0067). Western blot results showed that TGFBR1 expression significantly decreased in cervical cancer cells after let-7a-5p mimic treatment (P = 0.0048) and significantly increased after let-7a-5p mimic inhibitor treatment (P = 0.0003).Conclusionslet-7a-5p represents the independent novel anti-oncogenes in cervical cancer, which can regulate TGF-β1/TGFBR1/pSmad3 cell pathway and interfere with the proliferation of cervical cancer cells. Therefore, let-7a-5p can serve as a novel potential therapeutic target for the treatment of cervical cancer. (AU)