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Introduction: Cervical carcinoma is the second commonest malignancy among females worldwide. In India, about 365.71 million women aged over 15 years are more vulnerable to cervical carcinoma. Risk factors may include immunodeficiency diseases, herpes, smoking and oral contraceptives. Scientific literature has documented that type 2 diabetes mellitus (T2DM) could aggravate the risk of some malignancies (hepatic, pancreatic, endometrial). This study aimed to evaluate the potential association between cervical carcinoma and diabetes mellitus in women. Material and Methods: Patients with cervical carcinoma, with or without diabetes, were assigned to two groups based on attainment of menopause. SPSS version 11.5 was used for data analysis. Odds ratios were calculated, and the chi-square test was used. P-values ≤ 0.05 were considered statistically significant. Results: It was observed that 29% of patients with cervical cancer were sixty to seventy years old, with a majority (40%) of them being multiparous. Though the association of body mass index as a risk factor for diabetic patients with cervical carcinoma was not significant in pre-and post-menopausal age groups, T2DM in cervical carcinoma is a useful prognostic indicator. Conclusions: Diabetic females after attaining menopause have a higher risk of developing cervical carcinoma and therefore should mandatorily receive routine screening. Future research with a longer timeframe is needed in order to generalize the results. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of systemic immune inflammation index (SII) combined with serum squamous cell carcinoma antigen (SCCA) and vascular endothelial growth factor-C (VEGF-C) in evaluating the risk of postoperative recurrence in patients with human papillomavirus (HPV)-positive cervical cancer undergoing radical resection. Methods: A total of 160 patients with HPV-positive cervical cancer in Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology from January 2019 to October 2021 were selected as the study subjects. According to the 2-year follow-up after operation, the recurrence was counted, and patients were divided into recurrence group and non-recurrence group, the clinicopathological data and levels of SII, SCCA and VEGF-C were compared between two groups. The influencing factors of postoperative recurrence in patients with HPV-positive cervical cancer were analyzed by multivariate Logistic regression. Results: SII, SCCA, VEGF-C in recurrence group were significantly higher than those in non-recurrence group (P<0.05). FIGO stage, lymph node metastasis, SII, SCCA, VEGF-C were the influencing factors of postoperative recurrence in patients with HPV-positive cervical cancer (P<0.05). Conclusions: SII, SCCA, and VEGF-C are significantly elevated in HPV positive cervical cancer patients with recurrence after radical surgery, and are independent factors for postoperative recurrence in HPV positive cervical cancer patients, joint testing helps evaluate the risk of recurrence in patients. [ABSTRACT FROM AUTHOR]

To investigate the value of amide proton transfer weighted (APTw) combined with diffusion kurtosis imaging (DKI) in quantitative prediction of lymph node metastasis (LNM) in cervical carcinoma (CC). Data of 19 LNM(+) and 50 LNM(−) patients with CC were retrospectively analyzed. 3.0 T MRI scan was performed before the operation, including APTw and DKI. After post-processing, quantitative magnetization transfer ratio asymmetric at 3.5 ppm [MTRasym (3.5 ppm)], mean kurtosis (MK), and mean diffusivity (MD) maps were obtained. The MTRasym(3.5 ppm), MK, and MD values were respectively measured by two observers, and intra-class correlation coefficients (ICC) were used to test the consistency of the results. The independent samples t -test or Mann-Whitney U test was used to compare the differences in the values of each parameter. The ROC curve was used to analyze the predictive performance of parameters with significant differences and their combination parameter. The two observers had good agreement in the measurement of each data (ICC > 0.75). The MTRasym(3.5 ppm) and MK values of the LNM(+) group(3.260 ± 0.538% and 0.531 ± 0.202) were higher than those of the LNM(−) group(2.698 ± 0.597% and 0.401 ± 0.148) (P < 0.05), while there was no significant difference in MD values between the two groups (P > 0.05). The area under the curves (AUCs) of MTRasym(3.5 ppm), MK value, and MTRasym(3.5 ppm) + MK value were 0.763, 0.716, and 0.813, respectively, when predicting LNM status of CC. APTw and DKI can quantitatively predict LNM status of CC, which is of importance in clinical diagnosis and treatment. • APT weighted imaging is a novel molecular MR imaging method based on the chemical exchange saturation transfer mechanism. • DKI is a MR imaging that directly estimates and quantifies the non-Gaussian nature of water molecule diffusion in the body. • Our study shows that APT weighted imaging and DKI can quantitatively predict LNM status of CC. [ABSTRACT FROM AUTHOR]

Background: The roles of low molecular mass polypeptide 2 (LMP2) and transporter-associated with antigen processing (TAP2) in tumorigenesis are controversial. Here we aimed to explore the effect of LMP2 and TAP2 on the oncogenesis and metastasis of cervical cancer cells. Methods: The expressions of LMP2 and TAP2 in cervical cancer and normal tissues were determined by qPCR. Plate colony formation, cell counting kit-8 analysis and in vivo tumor xenograft assays were used to detect the tumor growth. Wound healing and transwell assays were used to detect the metastasis of cervical cancer. Gelatin zymography and western blotting assays were used to detect the effect of LMP2 and TAP2 on the EMT and Wnt/β-catenin pathway in cervical cancer cells. Results: In the present study, we reported that LMP2 and TAP2 levels were overexpressed in cervical cancer. Overexpression of LMP2 and TAP2 impaired the proliferation of Hela cells. In vivo studies substantiated that LMP2 and TAP2 antagonized tumor growth. Likewise, LMP2 and TAP2 overexpression decreased the migration and invasion ability of Hela cells by regulating the process of epithelial-mesenchymal transition (EMT). Mechanically, LMP2 and TAP2 subverted the protein abundance of Wnt1 and β-catenin, thereby downregulating their downstream targets Cyclin D1 and c-Myc. In addition, Wnt1 overexpression partially rescued the observed consequences of ectopic expression of LMP2 and TAP2 in cervical cancer cells. Taken together, our study revealed that LMP2 and TAP2 suppress the oncogenesis and metastasis of cervical cancer cells by Wnt/β-catenin pathway and altering EMT. Conclusion: LMP2 and TAP2 may inhibit the oncogenesis and metastasis of cervical cancer cells by inhibiting the process of EMT and the Wnt/β-catenin signaling pathway, which may provide important insight into prospective targets for the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Introduction: WHO has recommended global action to eliminate cervical cancer by the 21st century. HIV-infected women are at increased risk of acquiring HPV infection, progressing to pre-invasive, and invasive cervical cancers. Objectives: The objective was to assess the frequency of and the risk factors for pap smears abnormalities in HIV-seropositive and HIV-seronegative women. Materials and methods: This retrospective case control study conducted in a Medical College Hospital from January 2016 to December 2019 included case records of 330 married women aged more than 19 years. About 270 participants were eligible for controls and 60 for cases. Demographic details, CD4 count, and pap smear findings were noted, and statistical analysis was carried out. Results: Pap smear abnormalities were noted in 13.3% of HIV-infected women and 1.85% of HIV-negative women. The preponderance of inflammatory smear was 61.7% among seropositive women and 47% among seronegative women. The mean CD4 count among HIV-positive women was 534.34 ± 242.24 and in 64.14%, the CD4 count was >400. No statistically significant association between the abnormal pap smear results and the age of the individual, parity, and age at first intercourse was noted. Conclusion: Abnormal cervical cytology was seven times higher in HIV-infected women when compared with HIV-negative women and immunosuppression may be the predominant risk factor leading to cytological abnormalities in HIV-infected women. HIV-positive women showing inflammatory smears need further evaluation. [ABSTRACT FROM AUTHOR]

Cervical cancer, the fourth most common cancer among females in the world, ranks the second in China. In advanced disease, metastases may be commonly present in the lungs, bones, liver and lymph nodes or elsewhere, but uncommon to the skin. In this report, a 63‐year‐old woman was diagnosed as stage IVB cervical squamous cell cancer in January 2021. The patient was scheduled for concurrent chemoradiotherapy; however, a metastatic lesion of skin was proved by biopsy during the process of treatment. She died 1 month after confirmed skin metastases. Cutaneous metastasis of cervical cancer may predict the mix of lymphatic and hematogenous metastasis and the rapid fatal termination. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the ability of the Venezia advanced multichannel tandem and ring applicator to consistently produce dosimetrically comparable plans utilizing a reduced number of needle channels, to reduce the risk of secondary complications when boosting cervical cancer treatments with high dose rate (HDR) brachytherapy. Methods: We evaluated 26 fractions from 13 patients who were treated with HDR brachytherapy using the Venezia (Elekta) applicator. The original plans included a full load of 12–16 needles, including both parallel and 30‐degree oblique needles. We replanned each original to nine new configurations, with a reduced number of two, three, four, or six needles. Comparisons included differences in percentage dose coverage to 90% of the high‐risk clinical target volume, and percentage dose to 2 cm3 of the bladder, rectum, sigmoid, and bowel. We considered new plans "passing" if they remained within our standards (D90 > 100%; D2 cm3 < 85% bladder, <65% rectum, sigmoid, bowel) or did not perform worse than original. Results: Removing only the two most anterior or the two most posterior needles from both sides showed 80.8% and 61.5% overall passing rate. Removal of the most anterior and posterior four needles together showed 65.4% overall passing rate. Removing all oblique needles showed 19.2% overall passing rate. Removing only left‐sided or only right‐sided oblique needles showed 46.2% and 23.1% overall passing, respectively. Removing only right‐sided or only left‐sided parallel needles separately showed 19.2% and 34.6% overall passing, respectively. Removing all parallel needles showed 11.5% overall passing rate. Conclusions: As only two replans required a full needle load to maintain dosimetric quality and 40 (76.9%), 36 (34.6%), 18 (69.2%), and 10 (19.2%) replans passed with 2, 3, 4, and 6 needles removed respectively, this indicates the potential for using a lesser number of interstitial needles during combined intracavitary and interstitial HDR brachytherapy while maintaining dosimetric quality. [ABSTRACT FROM AUTHOR]

Condensed abstract: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving imageguided intensity-modulated radiation therapy (IG-IMRT). This is the first head-tohead propensity score-matched, nationwide population-based cohort study evaluating this survival effect. The results revealed that pretreatment 18FDGPET- CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving radiotherapy or concurrent chemoradiotherapy, especially in the IG-IMRT era. Purpose: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving imageguided intensity-modulated radiation therapy (IG-IMRT). Therefore, in this propensity score-matched, population-based cohort study, we investigated these survival effects. Patients and methods: We included 4167 patients with stage IB-IVA cervical cancer receiving radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through the IG-IMRT technique. The patients were categorized into two 1:2 propensity score-matched groups depending on whether they underwent pretreatment 18FDG-PET-CT, and their outcomes were compared. Results: We included 2778 and 1389 patients with cervical cancer in the nonpretreatment and pretreatment PET-CT groups, respectively. Univariable and multivariable analyses revealed an association between pretreatment PET-CT and improved survival in the patients (in the adjusted model, the adjusted hazard ratio [aHR] was 0.88; 95% confidence interval [CI], 0.80-0.97: P = 0.010). Regardless of the cancer stage (early or advanced), pretreatment PET-CT was significantly superior to nonpretreatment PET-CT in terms of all-cause death (aHR, 0.78; 95% CI, 0.60-0.92; P = 0.013 and aHR, 0.90; 95% CI, 0.81-0.99; P = 0.039 for the early [IB-IIA] and advanced stages [IIB-IVA], respectively). Conclusions: Pretreatment 18FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving RT or CCRT, especially in the era of IG-IMRT. [ABSTRACT FROM AUTHOR]

Background: Preoperative prediction of clinical pathological indicators of cervical cancer (CC) is of great significance to the formulation of personalized treatment plans for CC. Purpose: To investigate magnetic resonance imaging (MRI) radiomics analysis for the evaluation of pathological types, tumor grade, FIGO stage, and lymph node metastasis (LNM) of CC. Material and Methods: A total of 235 patients with CC from three institutes were enrolled in the study. All patients underwent T2/SPAIR and contrast-enhanced T1-weighted (CE-T1WI) imaging scans before radical hysterectomy by pelvic lymph node dissection surgery. Radiomics features extracted from T2/SPAIR and CE-T1WI imaging were selected by the least absolute shrinkage and selection operator (LASSO) methods for further radiomics signature calculation. These radiomic features were used to construct regression and decision tree models to evaluate the performance of radiomic features in distinguishing clinicopathological indicators. Results: The area under the curve (AUC) of T2/SPAIR and CE-T1WI imaging were 0.777 and 0.750, respectively, for differentiating between adenocarcinoma and squamous cell carcinoma. From the two sequences, the AUC of the verification group that distinguished low FIGO stage from high FIGO stage was 0.716 and 0.676, respectively. The AUC for moderately well and poorly differentiated tumors were 0.729 on T2/SPAIR and 0.749 on CE-T1WI imaging. The AUC of the verification groups for LNM was 0.730 and 0.618 on T2/SPAIR and CE-T1WI imaging, respectively. Conclusion: MRI radiomics features can be used as a non-invasive method to evaluate the clinicopathological indexes of CC and provide an important auxiliary examination method for patients to determine individualized treatment plans before operation. [ABSTRACT FROM AUTHOR]

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Cervical carcinoma is a leading malignant tumor among women worldwide, characterized by the dysregulation of cell cycle. Cyclin-dependent kinase 6 (CDK6) plays important roles in the cell cycle progression, cell differentiation, and tumorigenesis. However, the role of CDK6 in cervical cancer remains controversial. Here, we found that loss of CDK6 in cervical adenocarcinoma HeLa cell line inhibited cell proliferation but induced apoptosis as well as autophagy, accompanied by attenuated expression of mammalian target of rapamycin complex 1 (mTORC1) and hexokinase 2 (HK2), reduced glycolysis, and production of protein, nucleotide, and lipid. Similarly, we showed that CDK6 knockout inhibited the survival of CDK6-high CaSki but not CDK6-low SiHa cervical cancer cells by regulation of glycolysis and autophagy process. Collectively, our studies indicate that CDK6 is a critical regulator of human cervical cancer cells, especially with high CDK6 level, through its ability to regulate cellular apoptosis and metabolism. Thus, inhibition of CDK6 kinase activity could be a powerful therapeutic avenue used to treat cervical cancers. [ABSTRACT FROM AUTHOR]

Background: Most commonly used diffusion-weighted imaging (DWI) models include intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), stretched exponential model (SEM), and mono-exponential model (MEM). Previous studies of the four models were inconsistent on which model was more effective in distinguishing cervical cancer from normal cervical tissue. Purpose: To assess the performance of four DWI models in characterizing cervical cancer and normal cervical tissue. Material and Methods: Forty-seven women with suspected cervical carcinoma underwent DWI using eight b-values before treatment. Imaging parameters, calculated using IVIM, SEM, DKI, and MEM, were compared between cervical cancer and normal cervical tissue. The diagnostic performance of the models was evaluated using independent t -test, Mann–Whitney U test, receiver operating characteristic (ROC) curve analysis, and multivariate logistic regression analysis. Results: All parameters except pseudo-diffusion coefficient (D*) differed significantly between cervical cancer and normal cervical tissue (P < 0.001). Through logistic regression analysis, all combined models showed a significant improvement in area under the ROC curve (AUC) compared to individual DWI parameters. The model with combined IVIM parameters had a larger AUC value compared to those of other combined models (P < 0.05). Conclusion: All four DWI models are useful for differentiating cervical cancer from normal cervical tissue and IVIM may be the optimal model. [ABSTRACT FROM AUTHOR]

Tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (TIE2)-expressing macrophages (TEMs) are an angiogenesis-promoting subset of tumor-associated macrophages that have been demonstrated to be increased in solid tumors and associated with the progression of cervical cancer. However, the induction mechanism of TEMs remains unclear. Here, based on multicolor immunofluorescence of 58 cervical cancer tissues and the GEPIA database, we found that TEMs were increased in TIE2-high cervical cancer and related to shorter survival. In vitro and in vivo experiments verified that exosomes derived from TIE2-high cervical cancer cells transferred TIE2 protein directly to macrophages, thereby inducing TEMs. Similar to primary TEMs, TEMs induced by tumor-derived exosomes promoted angiogenesis, could be induced by angiopoietin-2, and possessed an M2-like phenotype. In conclusion, exosomes derived from TIE2-high cervical cancer cells induce TEMs by directly transporting TIE2 to promote tumor angiogenesis. [ABSTRACT FROM AUTHOR]

Background: The width of red blood cell distribution (RDW) is correlated with some diseases, but its clinical value and prognostic role in cervical cancer is unclear. Methods: We used receiver operating characteristic curves to evaluate the diagnostic ability of RDW and other clinical parameters in cervical cancer based on a case–control design. Using retrospective data, we explored the correlation of RDW with overall (OS) and progression-free (PFS) survival using Kaplan–Meier analysis and univariate and multivariate Cox regression with the hazard ratio (HR) and 95% confidence interval (CI). A restricted cubic plot was used to evaluate the nonlinear association between RDW and prognosis risk. Results: RDW was significantly higher in cases than in controls (14.6± 1.7 vs 12.5± 1.8, P< 0.001). It showed high diagnostic accuracy for cervical cancer, with a sensitivity of 79.3%, specificity of 65.6%, and area under the curve of 0.802 (95% CI, 0.775– 0.827) with a cutoff value of 13.88. There was a significant positive correlation between RDW and C-reactive protein (r=0.434, P=0.023). Multivariate Cox regression indicated that it was independently associated with a poorer PFS (HR, 2.05; 95% CI, 1.25– 3.18, P< 0.001) and OS (HR, 2.73; 95% CI, 1.61– 4.64, P< 0.001). RDW> 14.66 showed a nonlinear increased risk for a poor PFS and OS. Conclusion: RDW is an easy, quick, and inexpensive tool for the early detection and risk management of cervical cancer. A greater RDW is associated with a poor prognosis in cervical cancer. [ABSTRACT FROM AUTHOR]

Growing evidence indicates that lncRNA colon cancer-associated transcript 2 (CCAT2) is associated with cancers. However, the clinical value of CCAT2 in cervical cancer (CC) remains unclear. In this study, serum CCAT2 level was detected by real-time quantitative PCR (RT-qPCR). Carbohydrate antigen 125 (CA125) and squamous-cell carcinoma antigen (SCC) were detected by electrochemiluminescence. A receiver operating characteristic (ROC) curve was utilized to estimate the diagnostic efficiency of CCAT2. Kaplan-Meier survival analysis and univariable and multivariable analyses were performed to assess the prognostic value of CCAT2. The relative expression level of CCAT2 in primary CC patients was significantly higher than that in cervical intraepithelial neoplasias (CIN) patients and healthy controls (both P < 0.001). CCAT2 relative expression was positively correlated with tumor Federation of Gynecology and Obstetrics (FIGO) stage, SCC-Ag and lymph node metastasis (LNM) (all P < 0.05). CCAT2 expression in recurrent/metastatic CC was significantly higher compared with primary CC (P < 0.0001) or operated CC (P < 0.0001) and during follow-up, CCAT2 expression was increased before surgery and decreased significantly after surgery (P < 0.0001). Furthermore, the overall survival rate of CC patients with high CCAT2 expression group markedly decreased as compared with that of low CCAT2 expression group (P = 0.026). Univariate analyses indicated that CCAT2 was a poor prognostic factor associated with overall survival (OS). Our study indicates that CCAT2 may be valuable in complementary diagnosis and monitoring of progression and prognosis of CC patients. Combined detection of CCAT2, CA125 and SCC can greatly improve the diagnostic efficiency of primary CC. [ABSTRACT FROM AUTHOR]

Lymph node metastasis (LNM) is an important prognostic factor in cervical cancer (CC). In early stages, the risk of LNM is approximately 3.7 to 21.7%, and the 5-year overall survival decreases from 80% to 53% when metastatic disease is identified in the lymph nodes. Few reports have analyzed the relationship between miRNA expression and the presence of LNM. The aim of this study was to identify a subset of miRNAs related to LNM in early-stage CC patients. Formalin-fixed paraffin-embedded tissue blocks were collected from patients with early-stage CC treated by radical hysterectomy with lymphadenectomy. We analyzed samples from two groups of patients—one group with LNM and the other without LNM. Global miRNA expression was identified by microarray analysis, and cluster analysis was used to determine a subset of miRNAs associated with LNM. Microarray expression profiling identified a subset of 36 differentially expressed miRNAs in the two groups (fold change (FC) ≥ 1.5 and p < 0.01). We validated the expression of seven miRNAs; miR-487b, miR-29b-2-5p, and miR-195 were underexpressed, and miR-92b-5p, miR-483-5p, miR-4534, and miR-548ac were overexpressed according to the microarray experiments. This signature exhibited prognostic value for identifying early-stage CC patients with LNM. These findings may help detect LNM that cannot be observed in imaging studies. [ABSTRACT FROM AUTHOR]

Background: In this trial, we aimed to assess the efficacy and safety of radiotherapy with nedaplatin or cisplatin in patients with locally advanced cervical cancer. Methods: We conducted an open-label, non-inferiority, phase III, randomized, controlled trial. Eligible patients with stage IIB-IVA cervical carcinoma were randomly assigned to receive either nedaplatin or cisplatin for two cycles concurrently with radiotherapy. We reported the therapy-associated harms and survival. The study was registered with chictr.org.cn, number ChiCTR1800020527. Results: We randomly assigned 68 patients to nedaplatin-based or cisplatin-based concurrent chemoradiotherapy. Study treatment was stopped early after a data analysis found a higher number of patients suffered severe hematologic harms in the nedaplatin group than in the cisplatin group. Patients in the nedaplatin group had a significantly higher frequency of grade 3-4 neutropenia (19·4% vs. 13%; P < 0·001), severe thrombocytopenia (16·1% vs. 4·3%), and grade 1-2 anemia (51·6% vs. 43·5%) than patients in the cisplatin group. The 1-year PFS and OS in the nedaplatin and cisplatin groups were similar. Conclusion: Our findings showed that nedaplatin-based concurrent chemoradiotherapy expressed remarkably higher severe hematologic harms which were mortal. Though the results were negative, the experiences and lessons we learned from it were important. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a common female malignant tumor. With the trend of younger onset, people pay more and more attention to it. Numberless evidence has been indicated that long non-coding RNAs (lncRNAs) can take part in progression of cancers and can exert the regulatory roles in assorted cancers. Nevertheless, the roles of FEZ family zinc finger 1-antisense RNA 1 (FEZF1-AS1) in CC cells are still undiscovered. Aim of the study. Thus, the central purpose of our research was to reveal the specific functions and molecular mechanisms of FEZF1-AS1 in CC cells. RT-qPCR was utilized to test FEZF1-AS1 expression in CC cells. In addition, functional assays were conducted to evaluate cell proliferation, apoptosis, and migration as well as invasion. In addition, mechanism experiments verified relationship among FEZF1-AS1, miR-367-3p and solute carrier family 12 member 5 (SLC12A5). FEZF1-AS1 was highly expressed in CC cells. Moreover, FEZF1-AS1 depletion suppressed proliferation, migration, invasion, and induced cell apoptosis. Importantly, mechanism experiments confirmed that miR-367-3p could bissnd to FEZF1-AS1 and SLC12A5. The rescue assays determined that FEZF1-AS1 could up-regulate SLC12A5 through binding to miR-367-3p. The up-regulated FEZF1-AS1 could accelerate the malignant behaviors of CC cells by miR-367-3p/SLC12A5 signal axis. [ABSTRACT FROM AUTHOR]

Objective: To explore correlation between red blood cell distribution width (RDW) and cervical carcinoma. Methods: 50 cervical carcinoma patients and 75 healthy controls from the First Affiliated Hospital of Soochow University from June 2020 to December 2020 were involved as the patients group and the control group respectively. Demographic data were collected from routine blood tests and biochemistry examination, the correlation of RDW with hemoglobin(Hb) and c-reactive protein(CRP) was evaluated by Spearman rank correlation, and receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of RDW for cervical carcinoma. Result: The levels of RDW, squamous cell carcinoma antigen (SCCA) and carcinoembryonic antigen (CEA) in patients with cervical carcinoma were higher than those in the controls. The levels of high-density lipoprotein(HDL), Albumin, Prealbumin, Hb, RBC and neuron-specific enolase (NSE) in patients were lower than those in the controls(all P<0.05). There was no statistical significance on the difference in other markers between the two groups (P>0.05). The AUC of RDW in the diagnosis of cervical carcinoma was 0.834. Based on Spearman's rank correlation coefficient analysis, RDW was positively correlated with Hb (r=0.434, P<0.05) and CRP(r=0.366, P<0.05) RDW, and was negatively correlated with hematocrit(r=-0.363, P<0.05), in cervical carcinoma group, cervical carcinoma subgroup I-II and III-IV were higher than the control group (P < 0.05). Conclusions: Elevated RDW is associated with the occurrence of cervical carcinoma, and it may have clinical value in the diagnosis of cervical carcinoma and the course of reaction. [ABSTRACT FROM AUTHOR]

Background: Through Increased education, access to care, and the expansion of screening and vaccination programs, reductions in cervical cancer incidence and mortality may be achieved. Aim and Objectives: the aim of the study was to determine the clinicoepidemiological features and treatment outcome in cancer cervix at clinical oncology department of Ain Shams University Hospital. Subjects and Methods: This retrospective analytical study included consecutive adult female patients ≥ 18 years with pathologically confirmed cervical cancer presented to the Clinical Oncology Department, Ain Shams Faculty of Medicine, Cairo, Egypt from January 2016 to December 2020. Results: Most of the patients (71.3%) were under 60years, and the median age at diagnosis was 53 years. In our cohort, about 54.5 % of patients were postmenopausal, with the median age of menopause around 51.0 years. In most cases, the age of menarche was between 9 and 12 years. 94.1.0 % of the patients were married, and most of them got married after reaching the age of 18 years (74.2%). In our cohort, CCRTH improved both DFS and OS for adjuvant groups as well as PFS and OS for patients who received definitive treatment. Univariate analysis including age, menopausal status, sociodemograhic data, tumor characteristics, FIGO sataging and treatment received showed that significant risk factors for reduced PFS and OS of patients who received palliative treatment was Diabetus mellitus as a comorbidity. Conclusion: This data emphasizes that patient in rural setting present at later stages which could be improved by creating awareness in rural women, and help accessing adequate screening measures. [ABSTRACT FROM AUTHOR]

Summary: Immune checkpoint therapy to reverse natural killer (NK) and T cell exhaustion has emerged as a promising treatment in various cancers. While anti‐programmed cell death 1 (PD‐1) pembrolizumab has recently gained Food and Drug Administration (FDA) approval for use in recurrent or metastatic cervical cancer, other checkpoint molecules, such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine‐based inhibition motif (ITIM) domains (TIGIT) and T cell immunoglobulin and mucin‐domain containing‐3 (Tim‐3), have yet to be fully explored in this disease. We report expression of TIGIT, Tim‐3 and PD‐1 on subsets of peripheral blood NK (CD56dim/negCD16bright/dim/neg and CD56brightCD16dim/neg) and T cells. The percentages of these cells were increased in women with cervical cancer and pre‐malignant lesions. PD‐1+ NK and T cells were likely to co‐express TIGIT and/or Tim‐3. These cells, with an apparently 'exhausted' phenotype, were augmented in patients. A subset of cells were also natural killer group 2 member D (NKG2D)‐ and DNAX accessory molecule 1 (DNAM‐1)‐positive. PD‐1int and PD‐1high T cells were notably increased in cervical cancer. Soluble programmed cell death ligand 1 (PD‐L1) was higher in cancer patient blood versus healthy donors and we observed a positive correlation between sPD‐L1 and PD‐1+ T cells in women with low‐grade lesions. Within the cancer group, there were no significant correlations between sPD‐L1 levels and cervical cancer stage. However, when comparing cancer versus healthy donors, we observed an inverse association between sPD‐L1 and total T cells and a correlation between sPD‐L1 and CD56dim NK cells. Our results may show an overview of the immune response towards pre‐cancerous lesions and cervical cancer, perhaps giving an early clue as to whom to administer blocking therapies. The increase of multiple checkpoint markers may aid in identifying patients uniquely responsive to combined antibody therapies. [ABSTRACT FROM AUTHOR]

Aim: To investigate the diagnostic value of acoustic radiation force impulse imaging in the detection of cervical cancer, and to assess the contribution of this imaging method in distinguishing histological subtypes of cervical carcinoma.Materials and Methods: Twenty four patients with malignant cervical mass and 25 healthy volunteers were included in this prospective study. Ultrasonographic evaluation were performed using a 3.5–6-MHz convex abdominal transducer and adequate software for performing elastographic examinations in quantitative acoustic radiation force impulse mode (Virtual Touch Quantification®). Every examination consisted of at least three independent shear wave velocity measurements. The mean shear wave velocity values were calculated, and used for statistical analysis. Postoperative pathology results of the lesions were used as the reference standard.Results: The mean shear wave velocity values were calculated as 2.79±1.03 m/s in cervical carcinomas, and as 1.86±0.62 m/s in control group. The mean shear wave velocity value of cervical carcinomas was significantly higher than the control group (p=0.003). The mean shear wave velocity values in squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma subtypes were calculated as 2.78±0.93 m/s, 3.16±1.46 m/s, and 1.90±0.21 m/s, respectively. There were no significant differences between cervical carcinoma subtypes in terms of their shear wave velocity values (p=0.247).Conclusion: Acoustic radiation force impulse imaging is a non-invasive and cost-effective, promising adjunct modality that enables objective quantitative measurement, which may contribute to the diagnosis of malignant cervical masses. [ABSTRACT FROM AUTHOR]

Background: Factors contributing to the pathogenesis and progression of cervical cancer include poor attitude to screening and health intervention, late presentation, among others. Mutations in p53 gene have been attributed to several cancer cases. The present study was designed to find relationships between the mutation patterns in p53 gene and cervical carcinoma staging. Such knowledge could contribute to early diagnosis of cervical cancer. Results: From the sequence analysis of p53 gene fragment isolated by polymerase chain reactions (PCR), nineteen (19) polymorphic variants were identified. Missense mutations occurred in 47% of the samples, 32% were silent mutations, 16% were frameshift mutations and 5% nonsense mutations. Socio-biological characteristics of the study participants revealed that 60% have husbands with multiple sexual partners and that only 23.3% of the participants have ever had the Papanicolaou (Pap) smear test prior to diagnosis, whilst 20% were unaware of the screening test. Conclusions: Increased severity of cervical carcinoma staging as revealed from the histopathological analysis was found to be associated with accumulation of higher levels of mutations in the p53 gene. Molecular analysis of p53 gene mutations may prove useful as a screening biomarker for cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is one of the most common gynecologic tumors. Evidence is accumulating that long non-coding RNAs participate in the pathogenesis of cancers, but the expression and role of lncRNA LINC00313 in cervical carcinoma is not reported. Methods: We measured the expression levels of LINC00313 in clinical samples of cervical carcinoma and investigated the function of LINC00313 in the regulation of proliferation, metastasis, and EMT. Luciferase reporter assay was employed to explore the molecular regulation process of LINC00313. Results: Our data showed that the levels of LINC00313 in cervical carcinoma tissues and cells were significantly up-regulated. Functionally, LINC00313 accelerated the progression, migration, and EMT of SiHa and Hela cells. Luciferase reporter assay confirmed that miR-4677-3p/CDK6 regulatory axis is the direct downstream of LINC00313. Functional gain- and loss-of-function strategies further showed that LINC00313 induced the up-regulation of CDK6 expression through competitive binding with miR-4677-3p, leading to promote the progression of cervical carcinoma. Conclusion: Our results demonstrated that LINC00313 accelerated the progression of cervical cancer through the miR-4677-3p/CDK6 regulatory axis. LncRNA LINC00313 may serve as a potential target for the diagnosis and treatment of cervical carcinoma. [ABSTRACT FROM AUTHOR]

Background: To validate markers for cervical carcinoma (CC) and precancerous lesions related with HPV infections. Methods: Three different cervical cancer cell lines C-33A, SiHa and Caski were used for secretome profiling by label-free quantitative proteomics. Cervical exfoliated cells and matching serum samples were collected from 284 patients with normal control (n = 75, 26.41 %), precancerous lesions (n = 88, 30.99 %) and early stage cervical squamous carcinoma (n = 121, 42.61 %). HPV subtyping and quantification was performed by PCR and hybridization. 20 candidate proteins identified in previous screening studies (tissue, plasma, cells) were quantified by ELISA. Finally, highly quantitative parallel reaction monitoring mass spectrometry was used to assess the specificities and sensitivities of candidate serum markers. Results: While CC was found to be associated with high-risk HPV subtypes, serum antibodies for high risk HPV were not significantly related to the progression of cervical cancer. Significant differences between patient groups were detected for the four proteins CLU, APOA4, APOE and MLH3, but none would allow clinical application due to insufficient sensitivity and specificity and large variability. Subsequent proteomic secretome analysis of cervical cancer cell lines identified a set of 729 common proteins. Cross referencing this dataset with ELISA measurements revealed six candidate proteins of which two, FBLN1 and ANT3, showed co-occurrence with HPV infection (75.7 % and 85 %, respectively) and had promising diagnostic ability in terms of sensitivity and specificity. After the loss of E6/E7 by using CRISPR/Cas9 gene editing, the content of ANT3 and FBLN1 in KoE6/E7 SiHa were downregulated, which indicated the expression of ANT3 and FBLN1 in cervical cancer may be affected by HPV infection. Conclusions: FBLN1 and ANT3 might be potential tumor- and HPV-associated serum markers. [ABSTRACT FROM AUTHOR]

In human papillomavirus (HPV) cervical cancer screening, cytology is used as triage to counter the low specificity of HPV testing. VALID‐SCREEN is a EU‐multicenter, retrospective study conducted to evaluate the clinical performance of the FAM19A4/miR124‐2 methylation‐based molecular triage test as a substitute or addition to cytology as reflex testing of HPV screen positive women. FAM19A4/miR124‐2 methylation test (QIAsure Methylation Test) was evaluated in 2384 HPV‐positive cervical screening samples, from women 29‐76 years of age, derived from four EU countries. Specimens were collected in ThinPrep or SurePath media, HPV‐status, concurrent cytology, and histology diagnosis were provided by the parent institutes. The control population consisted of women with no evidence of disease within 2 years of follow‐up. A total of 899 histologies were retrieved; 527 showed no disease, 124 CIN2 (5.2%), 228 CIN3 (9.6%) and 20 cervical cancers (0.8%); 19 of 20 screen‐detected cervical cancers were found methylation‐positive (sensitivity 95%). Overall specificity of FAM19A4/miR124‐2 methylation test was 78.3% (n = 2013; 95%CI: 76‐80). The negative predictive value of hrHPV positive, methylation‐negative outcomes were 99.9% for cervical cancer (N = 1694; 95%CI: 99.6‐99.99), 96.9% for ≥CIN3 (95%CI: 96‐98), and 93.0% for ≥CIN2 (95%CI: 92‐94). Overall sensitivity for CIN3 using FAM19A4/miR124‐2 methylation test was 77% (n = 228; 95%CI: 71‐82). CIN3 sensitivity was uniform between centers independent of sample collection medias, DNA extraction methods and HPV screening tests. Being objectively reported compared to the subjectivity of cytology, equally performing across settings and screening methods, the FAM19A4/miR124‐2 methylation constitute an alternative/supplement to cytology as triage method to be investigated in real‐life pilot implementation. What's new? In HPV screening for cervical cancer, cytology has been used to triage those women who are hrHPV‐positive. However, cytology is subjective, and skilled cytologists are often in short supply. A molecular test using specific biomarkers might offer better results. In this large European study, the authors found that a new standardized test for the methylation biomarker combination FAM19A4/miR124‐2 did indeed yield results that were equal to or better than triage by cytology, in determining which hrHPV‐positive women should be referred for colposcopy. [ABSTRACT FROM AUTHOR]

Isolated internal iliac artery aneurysms are rarely described in the available literature. The paper presents a case of a 70-year-old female with idiopathic thrombocytopenia, squamous cell cervical carcinoma, and saccular aneurysm of the left internal iliac artery, detected in magnetic resonance. The review of aneurysm of the common, external and internal iliac arteries is added. [ABSTRACT FROM AUTHOR]

Cervical cancer is the second most common malignant tumour threatening women's health. In recent years, heavy-ion beam therapy is becoming a newly emerging therapeutic mean of cancer; however, radio-resistance and radiation-induced damage constitute the main obstacles for curative treatment of cervical cancer. Therefore, to identify the radiosensitizers is essential. Here, we investigated the effects of Wnt signalling pathway on the response of 12C6+ radiation in HeLa cells. XAV939, an inhibitor of Wnt signalling pathway, was added two hours before 12C6+ radiation.12C6+ radiation inhibited the viability of HeLa cells in a time-dependent manner, and inhibiting Wnt signalling using XAV939 significantly intensified this stress. Meanwhile, 12C6+ radiation induced a significant increased cell apoptosis, G2/M phase arrest, and the number of γ-H2AX foci. Supplementation with XAV939 significantly increased the effects induced by 12C6+ radiation alone. Combining XAV939 with 12C6+ irradiation, the expression of apoptotic genes (p53, Bax, Bcl-2) was significantly increased, while the expression of Wnt-related genes (Wnt3a, Wnt5a, β-catenin, cyclin D1 and c-Myc) was significantly decreased. Overall, these findings suggested that blockage of the Wnt/β-catenin pathway effectively sensitizes HeLa cells to 12C6+ irradiation, and it may be a potential therapeutic approach in terms of increasing the clinical efficacy of 12C6+ beams. [ABSTRACT FROM AUTHOR]

To analyze the effects of thalidomide combined with radiotherapy on the expression of the VEGF, bFGF and TNF-α in nude mice with cervical cancer xenografts, and to explore the mechanism of their sensitizing effect. Twenty-four nude mice were selected, and 0.2 mL Hela cell suspension was injected subcutaneously into the left armpit for modeling. The nude mice with successful modeling were randomly divided into the control group (CG), the thalidomide group (TG), the radiotherapy group (RG) and the combined treatment group (TG+RG), 6 per group. Each group was given carboxymethylcellulose sodium, thalidomide solution, radiotherapy, thalidomide solution+radiotherapy. After 14 days of treatment, the tumor volume, tumor inhibition rate, delayed tumor growth time (TGD) and radiosensitization were measured Ration, Ser), necrosis degree of tumor cells, microvessel density, VEGF, bFGF in serum and VEGF, bFGF, TNF-α in tumor tissue were detected. The radiosensitization effect and mechanism of thalidomide combined with radiotherapy on cervical cancer transplanted tumor in nude mice were analyzed. After treatment 14 d, compared with the control group, the growth rate of tumor volume in the thalidomide group, the radiotherapy group and the combined treatment group was significantly slower, tumor inhibition rate was significantly higher, TGD was significantly longer, the number of necrotic cells was significantly increased, microvascular density, serum and the expression of VEGF, bFGF, TNF-α in tumor group were significantly reduced, the difference was statistically significant (P<0.05). Compared with the thalidomide group and the radiotherapy group, the tumor weight in the combined therapy group was significantly slower, the tumor inhibition rate was significantly higher, the TGD was significantly longer, the number of necrotic cells was significantly increased, the expression of VEGF, bFGF and TNF-α in microvessel density, serum and tumor group were significantly lower, the difference was statistically significant (P<0.05). The sensitivity ratio (SER) is greater than 1. Thalidomide could significantly enhance the effect of radiotherapy on cervical cancer xenografts in nude mice, which may be related to its significant reduction in the expression of VEGF, bFGF, and TNF-α. [ABSTRACT FROM AUTHOR]

Widespread adoption of primary human papillomavirus (HPV)‐based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124‐2 genes has shown promise for the triage of high‐risk (hr) HPV‐positive women. In our study, we assessed the consistency of FAM19A4/miR124‐2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation‐specific PCR (qMSP)‐based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7–99.2) tested FAM19A4/miR124‐2 methylation‐positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124‐2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV‐negative carcinomas. These results indicate that a negative FAM19A4/miR124‐2 methylation assay result is likely to rule out the presence of cervical cancer. What's new? Methylation analysis of host cell genes is a promising strategy for the triage of women who test positive for high‐risk human papillomavirus (hrHPV). Its ability to consistently detect cervical cancer, however, warrants further evaluation. In this retrospective cross‐sectional study of more than 500 cervical cancer cases worldwide, methylation analysis using FAM19A4 and miR124‐2 genes successfully detected the vast majority of cervical carcinomas. Detection by FAM19A4/miR124‐2 methylation analysis was consistent regardless of multiple factors, including hrHPV status and genotype, cancer histotype, sample type, and geographical region. The findings suggest that a negative FAM19A4/miR124‐2 methylation test result is likely to rule out cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the perioperative complications of patients with cervical cancer who are treated with robot-assisted radical hysterectomy (RRH) and to further evaluate the safety of patients undergoing NACT. Methods: A total of 805 consecutive cervical cancer patients undergoing RRH were involved in this report. Their clinical characteristics were retrieved from hospital medical records. Perioperative complications were subdivided into intraoperative and postoperative complications, which were graded according to the Clavien–Dindo classification (CDC), and the complications of grade III and above were defined as severe complications. Furthermore, the two-level logistic regression model was used to estimate the risk factors of perioperative and severe complications and to further confirm the relationship between NACT and perioperative and severe complications. Results: The perioperative complication rate and severe complications were 45.09% and 7.83%, respectively. Poorly differentiated tumor and NACT were identified as independent risk factors for perioperative complications by multifactor analysis. Furthermore, we concentrated on the relations between NACT and complications. The risk of perioperative complications of the group with NACT (OR = 11.08, 95% CI: 5.70– 21.54) was significantly higher than the group without NACT, especially in postoperative complications (OR=17.65, 95% CI: 8.63– 36.08), even after adjusting confounding factors. However, there was no statistically significant difference in terms of severe complications (OR=1.68, 95% CI: 0.64– 4.41) and intraoperative complications (OR=0.51, 95% CI: 0.18– 1.41). Moreover, as the times of NACT increase, the impact on perioperative complications is more pronounced. A similar trend was observed in postoperative complications, while this statistical difference was still not observed in intraoperative and severe complications. Conclusion: This result demonstrates the feasibility and safety of RRH of cervical carcinoma after NACT in generally, since it only causes mild complications, not severe complications. [ABSTRACT FROM AUTHOR]

Purpose: Emerging evidence have revealed significant contributions of CUB domain-containing protein-1 (CDCP1) in tumorigenesis, including colon, renal, ovarian, pancreatic, prostate and breast cancers. However, the roles of CDCP1 in cervical cancer (CC) still remain elusive. Materials and Methods: Quantitative reverse transcription polymerase chain reaction, immunohistochemistry and Western blotting were used to confirm the expression of CDCP1 in CC tissues compared with matched non-tumor tissues. In vitro, gain-of-function and loss-of-function studies were used to investigate the biological function and underlying mechanism of CDCP1 in cervical carcinogenesis. Furthermore, tumor growth was evaluated using a xenogenous subcutaneously implant model of CC cells in vivo. Results: Here, we confirmed that CDCP1 was significantly increased in human CC both in mRNA and in protein levels compared to normal cervical tissues. Furthermore, we demonstrated that increased CDCP1 expression promotes proliferation, migration, invasion and mediates the epithelial-to-mesenchymal transition phenotype in HeLa and C33A cells. Also, CDCP1 knockdown reverses all the effects of enhanced CDCP1 on cell behavior in SiHa and Caski cells. Importantly, the suppressive expression of CDCP1 repressed tumor growth in a mouse xenograft model of CC. Conclusion: In summary, our current study results provide novel insights into the role of CDCP1 in CC progression. Potentially, CDCP1 might serve as a diagnostic biomarker and a novel therapeutic target for CC. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical effect of acupuncture on the treatment of urinary retention after cervical cancer surgery. Methods: A total of 80 patients with urinary retention after cervical cancer treated in our hospital from August 2015 to August 2016 were selected and divided into observation group and control group according to odd and even number method and each group had a total of 40 cases. Patients in the control group were given conventional treatment and the observation group was given acupuncture treatment. We compared the clinical efficacy of the two groups, catheter retention time, residual urine volume, urinary tract infection and urinary retention. Results: The total effective rate of the observation group was 97.50% which was higher than that of the control group (80%). The observation group's catheter retention time 10.97 ± 2.13 days, residual urine 57.01 ± 13.11 mL and other indicators were lower than the control group 16.13 ± 3.61 days and 93.96 ± 23.97 mL. The incidence of urinary tract infection (2.50%) and urinary retention (0.00%) in the observation group were lower than those in the control group (10.00, 20.00%). Conclusions: While acupuncture for the treatment of postoperative urinary retention of cervical cancer continues to develop and innovate, this study demonstrates that acupuncture is more effective than the conventional western medicine treatment method. [ABSTRACT FROM AUTHOR]

To determine the value of the tumor-stroma ratio (TSR) while identifying prognostic factors in patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIIC squamous cell carcinoma of the cervix following primary radical surgery. Three hundred eighty-four patients with node-positive squamous cell carcinoma of the cervix (2018 FIGO stage IIIC) who underwent radical surgery between January 2005 and December 2016 were included in this retrospective study. The TSRs were assessed on hematoxylin and eosin-stained tumor slides and classified as stroma-low (<50% stroma) or stroma-high (≥50% stroma). Sixty-seven patients were categorized as stroma-high; they had shorter disease-free survival (DFS) and overall survival (OS) periods than did their stroma-low counterparts. On multivariate analysis, a tumor size ≥4 cm, ≥3 metastatic lymph nodes, and stroma-high status were independent predictors of shorter DFS and OS. These factors were incorporated into a prognostic scoring system in which patients were categorized into low- (score 0), intermediate- (score 1), and high-risk (scores 2–3) groups. The scoring system differentiated DFS and OS well (C-index = 0.65, 95% confidence interval, 0.59–0.72; and C-index = 0.65, 95% confidence interval, 0.59–0.72, respectively). The TSR is an independent prognostic factor, and our prognostic scoring system that incorporates this parameter exhibits good discriminative ability for both recurrence and survival in patients with 2018 FIGO stage IIIC cervical cancer after radical surgery. The TSR is a potentially novel clinicopathological variable for predicting the prognoses of these patients contingent on the validation of our findings. • The tumor-stroma ratio (TSR) is prognostic in patients with various cancers, but its role in cervical cancer is uncertain. • We investigated the role of the TSR in patients with FIGO stage IIIC cervical cancer who underwent radical surgery. • A low TSR, tumor size ≥4 cm, and ≥3 metastatic lymph nodes predicted poorer survival on multivariate analysis. • A prognostic score derived from these factors was able to categorize patients according to recurrence and survival well. • The TSR as well as our prognostic scoring system may be valuable for outcome prediction treatment decisions. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to compare 3D dose volume histogram (DVH) parameters of bladder and other organs at risk with different bladder filling protocol during high-dose-rate intracavitary brachytherapy (HDR-ICBT) in cervical cancer, and to find optimized bladder volume. Material and methods : This dosimetric study was completed with 21 patients who underwent HDR-ICBT with computed tomography/magnetic resonance compatible applicator as a routine treatment. Computed tomography planning was done for each patient with bladder emptied (series 1), after 50 ml (series 2), and 100 ml (series 3) bladder filling with a saline infusion through the bladder catheter. Contouring was done on the Eclipse Planning System. 7 Gy to point A was prescribed with the standard loading patterns. Various 3D DVH parameters including 0.1 cc, 1 cc, 2 cc doses and mean doses to the OAR’s were noted. Paired t-test was performed. Results : The mean (± SD) bladder volume was 64.5 (± 25) cc, 116.2 (± 28) cc, and 172.9 (± 29) cc, for series 1, 2, and 3, respectively. The 0.1 cm 3 ,1 cm 3 , 2 cm 3 mean bladder doses for series 1, series 2, and series 3 were 9.28 ± 2.27 Gy, 7.38 ± 1.72 Gy, 6.58 ± 1.58 Gy; 9.39 ± 2.28 Gy, 7.85 ± 1.85 Gy, 7.05 ± 1.59 Gy, and 10.09 ± 2.46 Gy, 8.33 ± 1.75 Gy, 7.6 ± 1.55 Gy, respectively. However, there was a trend towards higher bladder doses in series 3. Similarly, for small bowel dose 0.1 cm 3 , 1 cm 3 , and 2 cm 3 in series 1, 2, and 3 were 5.44 ± 2.2 Gy, 4.41 ± 1.84 Gy, 4 ± 1.69 Gy; 4.57 ± 2.89 Gy, 3.78 ± 2.21 Gy, 3.35 ± 2.02 Gy, and 4.09 ± 2.38 Gy, 3.26 ± 1.8 Gy, 3.05 ± 1.58 Gy. Significant increase in small bowel dose in empty bladder (series 1) compared to full bladder (series 3) (p = 0.03) was noted. However, the rectal and sigmoid doses were not significantly affected with either series. Conclusions : Bladder filling protocol with 50 ml and 100 ml was well tolerated and achieved a reasonably reproducible bladder volume during cervical brachytherapy. In our analysis so far, there is no significant impact of bladder filling on DVH parameters, although larger bladders tend to have higher doses. Small bowel doses are lesser with higher bladder volumes. Further evaluation and validation are necessary.

Neoadjuvant chemotherapy (NACT) followed by radical surgical hysterectomy and pelvic lymph node dissection is considered an effective method to treat patients with bulky stage IB–IIA cervical cancer, but not all patients benefit from NACT. Apoptotic proteins play important roles in the progression of chemotherapy, and second mitochondria-derived activator of caspase (Smac) may have a cooperative relationship with Omi/HtrA2, leading to carcinogenesis and chemotherapy resistance. Chemosensitivity is an important prognostic factor for cervical cancer patients. The aim of this study was to evaluate the significance of Smac, survivin, X-linked inhibitor-of-apoptosis protein (XIAP), and Omi/HtrA2 expression in predicting the response to neoadjuvant chemotherapy and the prognostic significance of te expression of these proteins in cervical cancer patients. Our findings showed that low expression levels of survivin and high expression levels of Omi/HtrA2 in chemotherapy-responsive cervical carcinoma patients significantly increased chemosensitivity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Worldwide, cervical cancer is the fouth leading cause of deaths in gynecological oncology. Although the causes of cervical cancer have been extensively investigated, understanding of its exact pathogenesis remains incomplete. OBJECTIVE: This study aimed to identify alterations of genome and transcriptome of HPV associated cervical cancer pathogenesis using multi-omics approaches. METHODS: Cervical cancer and matched adjacent non-tumor specimens of one HPV16+ and two HPV- patients were sampled for whole-exome sequencing (WES) and RNA sequencing to characterize DNA mutations and gene expression profiles. WES and Affymetrix SNP 6.0 arrays data were analyzed from 6 HPV- and 93 HPV16+ cervical cancer patients in the cancer genome atlas (TCGA) database, as an independent validation group. RESULTS: WES identified 64 somatic mutation genes in tumors of 3 patients. HPV16+ tumor got fewer somatic mutated genes than HPV- tumors, which was validated by TCGA results. In this study, somatic mutated profile, CNV and gene expression heat map presented that HPV16+ tumors was distinct with HPV- tumors. The most significant altered pathways and GO terms were both related with cell cycle. Integrated analysis of multi-omics showed positive correlation between gene expression level and copy numbers. CONCLUSIONS: The results of this study provided novel insights into the pathogenesis of HPV associated cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Immunotherapeutic approaches have revolutionized oncological practice but are less evaluated in gynecological malignancies. PD-1/PD-L1 blockade in gynecological cancers showed objective responses in 13-17% of patients. This could be due to immunosuppressive effects exerted by gynecological tumors on the microenvironment and an altered tumor vasculature. In other malignancies, combining checkpoint blockade with radiation delivers benefit that is believed to be due to the abscopal effect. Addition of immune modulation agents has also shown to enhance immune checkpoint blockade efficacy. Therefore we designed a regimen consisting of PD-1 blockade combined with radiation, and different immune/environmental-targeting compounds: repurposed drugs, metronomic chemotherapy and a food supplement. We hypothesize that these will synergistically modulate the tumor microenvironment and induce and sustain an anti-tumor immune response, resulting in tumor regression.Methods: PRIMMO is a multi-center, open-label, non-randomized, 3-cohort phase 2 study with safety run-in in patients with recurrent/refractory cervical carcinoma, endometrial carcinoma or uterine sarcoma. Treatment consists of daily intake of vitamin D, lansoprazole, aspirin, cyclophosphamide and curcumin, starting 2 weeks before the first pembrolizumab dose. Pembrolizumab is administered 3-weekly for a total of 6 cycles. Radiation (3 × 8 Gy) is given on days 1, 3 and 5 of the first pembrolizumab dose. The safety run-in consists of 6 patients. In total, 18 and 25 evaluable patients for cervical and endometrial carcinoma respectively are foreseen to enroll. No sample size is determined for uterine sarcoma due to its rarity. The primary objective is objective response rate at week 26 according to immune-related response criteria. Secondary objectives include safety, objective response rate at week 26 according to RECIST v1.1, best overall response, progression-free survival, overall survival and quality of life. Exploratory, translational research aims to evaluate immune biomarkers, extracellular vesicles, cell death biomarkers and the gut microbiome.Discussion: In this study, a combination of PD-1 blockade, radiation and immune/environmental-targeting compounds is tested, aiming to tackle the tumor microenvironment and induce anti-tumor immunity. Translational research is performed to discover biomarkers related to the mode of action of the combination.Trial Registration: EU Clinical Trials Register: EudraCT 2016-001569-97 , registered on 19-6-2017. Clinicaltrials.gov: NCT03192059 , registered on 19-6-2017. [ABSTRACT FROM AUTHOR]

Background: Aberrant spliced isoforms are specifically associated with cancer progression and metastasis. The cytoplasmic adaptor CRKL (v-crk avian sarcoma virus CT10 oncogene homolog-like) is a CRK like proto-oncogene, which encodes a SH2 and SH3 (src homology) domain-containing adaptor protein. CRKL is tightly linked to leukemia via its binding partners BCR-ABL and TEL-ABL, upregulated in multiple types of human cancers, and induce cancer cell proliferation and invasion. However, it remains unclear whether signaling adaptors such as CRKL could regulate alternative splicing.Methods: We analyzed the expression level of CRKL in 305 cervical cancer tissue samples available in TCGA database, and then selected two groups of cancer samples with CRKL differentially expressed to analyzed potential CRKL-regulated alternative splicing events (ASEs). CRKL was knocked down by shRNA to further study CRKL-regulated alternative splicing and the activity of SR protein kinases in HeLa cells using RNA-Seq and Western blot techniques. We validated 43 CRKL-regulated ASEs detected by RNA-seq in HeLa cells, using RT-qPCR analysis of HeLa cell samples and using RNA-seq data of the two group of clinical cervical samples.Results: The expression of CRKL was mostly up-regulated in stage I cervical cancer samples. Knock-down of CRKL led to a reduced cell proliferation. CRKL-regulated alternative splicing of a large number of genes were enriched in cancer-related functional pathways, among which DNA repair and G2/M mitotic cell cycle, GnRH signaling were shared among the top 10 enriched GO terms and KEGG pathways by results from clinical samples and HeLa cell model. We showed that CRKL-regulated ASEs revealed by computational analysis using ABLas software in HeLa cell were highly validated by RT-qPCR, and also validated by cervical cancer clinical samples.Conclusions: This is the first report of CRKL-regulation of the alternative splicing of a number of genes critical in tumorigenesis and cancer progression, which is consistent with CRKL reported role as a signaling adaptor and a kinase. Our results underline that the signaling adaptor CRKL might integrate the external and intrinsic cellular signals and coordinate the dynamic activation of cellular signaling pathways including alternative splicing regulation. [ABSTRACT FROM AUTHOR]

Objective: To study the prevalence of high-grade cervical intraepithelial neoplasia (CIN) or worse in southern Thai women with atypical squamous cells of undetermined significance (ASC-US) from cervical cytology. Materials and Methods: The present study was a retrospective cross-sectional analytic study. Medical records from outpatient clinic of Department of Obstetrics and Gynecology between January 1, 2012 and October 31, 2017 were reviewed. Statistical analyses were performed. Results: Prevalence of high-grade CIN or worse in women with ASC-US from cervical cytology was 14.4%. Of these, 12.4% were high-grade CIN and 2.0% were cervical cancer. Multiple sexual partners was significantly associated with underlying high-grade CIN or higher (p<0.01). Conclusion: Prevalence of high-grade CIN or worse in southern Thai women with ASC-US from cervical cytology was 14.4% and multiple sexual partners was significantly associated with underlying high-grade CIN or worse in the present population. [ABSTRACT FROM AUTHOR]

Summary: Various studies revealed that elevated expression of CD97 in carcinomas is associated with the dedifferentiation, aggressiveness and metastasis of tumour. CD97 is a protein member of the epidermal growth factor seven‐transmembrane (EGF‐TM7) family of class II TM7 receptors. Our previous study suggested that the overexpression of CD97 in cervical cancer was correlated with the aggressiveness of the tumour and that CD97 might be an independent poor prognostic factor for cervical cancer patients. Based on these data, we have investigated the role of CD97 small isoform in cervical cancer proliferation, migration and invasion in vitro. Three cervical cancer cell lines were tested and the CD97 small isoform was found to be expressed predominantly in the SiHa cells. The mobile and invasive ability of different cervical cancer cell lines was not correlated positively with total CD97 protein expression but was with the level of the CD97 small isoform. Functional significance was assessed 48 hours after transient knockdown using siRNA targeting CD97 small isoform (CD97/EGF1,2,5) or a scrambled control sequence in cervical cancer cell lines. As a result, decreased ability of migration and invasion was found in CD97 small isoform RNAi cells, which showed, however, no change in cell proliferation. This study shed light on the role of the CD97 small isoform in tumour progression and provides a basis for further studies to determine its function in vivo. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cancer is a common malignant tumor in women; most cervical cancer patients are premenopausal. Ovarian resection or preservation remains controversial. The purpose of this study was to discover the risk factors for ovarian metastasis in women with stage I-II cervical cancer.Material and Methods: A total of 3292 women with cervical carcinoma who had undergone radical hysterectomy, with pelvic lymphadenectomy and bilateral oophorectomy or wedge resection of ovaries, were included in this multicenter retrospective study. We analyzed patients' demographics, International Federation of Obstetrics and Gynecology stage, and histopathologic records to determine clinicopathologic risk factors of ovarian metastasis.Results: Of the patients, 115 (3.49%) were confirmed to have ovarian metastasis. The ovarian metastasis rate was 2% (56/2794) for squamous cell carcinoma and 11.8% (59/498) for nonsquamous cell carcinoma. The risk factors independently associated with ovarian metastasis were histologic type (odds ratio [OR] 8.76, 95% CI 2.09-19.24), lymph node metastasis (OR 2.57, 95% CI 1.76-4.89), lymphovascular space invasion (OR 2.82, 95% CI 1.98-4.24), and corpus invasion (OR 6.34, 95% CI 2.37-11.42).Conclusions: The histologic type, lymph node metastasis, lymphovascular space invasion, and corpus invasion were independently associated with ovarian metastasis. Histologic type and corpus invasion were the most important risk factors. Therefore, we suggest that corpus invasion might be a strong contraindication for preservation of the ovaries. [ABSTRACT FROM AUTHOR]

Background/Aims: This study is aimed at identification of miR-195-5p/MMP14 expression in cervical cancer (CC) and their roles on cell proliferation and invasion profile of CC cells through TNF signaling pathway in CC. Methods: Microarray analysis, gene set enrichment analysis (GSEA) and DAVID were used to analyze differentially expressed miRNAs, mRNAs and signaling pathways. MiR-195-5p and MMP14 expression levels in CC cell were determined by qRT-PCR. Western blot was employed to measure MMP14 and TNF signaling pathway-relating protein level. Luciferase reporter system was used to confirm the targeting relationship between MMP14 and miR-195-5p. Cell proliferation and invasion was respectively deeded by CCK8, transwell. In vivo experiment was carried out to study the impact of MMP14 and miR-195-5p on CC development in mice. Results: The microarray analysis and the results of qRT-PCR determined that miR-195-5p was under-expressed and MMP14 was over-expressed in CC cells. GSEA and DAVID analysis showed that TNF signaling pathway was regulated by miR-195-5p/MMP14 and activated in cervical carcinoma cells. The miR-195-5p and MMP14 have a negative regulation relation. In vivo experiment found that down-regulated MMP14 and up-regulated miR-195-5p suppressed the tumor development. Conclusion: Our results suggest that MMP14 is a direct target of miR-195-5p, and down-regulated MMP14 and up-regulated miR-195-5p suppressed proliferation and invasion of CC cells by inhibiting TNF signaling pathway. [ABSTRACT FROM AUTHOR]