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cervical cancer - Top 30 Publications

Automatic labeling of molecular biomarkers of immunohistochemistry images using fully convolutional networks.

This paper addresses the problem of quantifying biomarkers in multi-stained tissues based on the color and spatial information of microscopy images of the tissue. A deep learning-based method that can automatically localize and quantify the regions expressing biomarker(s) in any selected area on a whole slide image is proposed. The deep learning network, which we refer to as Whole Image (WI)-Net, is a fully convolutional network whose input is the true RGB color image of a tissue and output is a map showing the locations of each biomarker. The WI-Net relies on a different network, Nuclei (N)-Net, which is a convolutional neural network that classifies each nucleus separately according to the biomarker(s) it expresses. In this study, images of immunohistochemistry (IHC)-stained slides were collected and used. Images of nuclei (4679 RGB images) were manually labeled based on the expressing biomarkers in each nucleus (as p16 positive, Ki-67 positive, p16 and Ki-67 positive, p16 and Ki-67 negative). The labeled nuclei images were used to train the N-Net (obtaining an accuracy of 92% in a test set). The trained N-Net was then extended to WI-Net that generated a map of all biomarkers in any selected sub-image of the whole slide image acquired by the scanner (instead of classifying every nucleus image). The results of our method compare well with the manual labeling by humans (average F-score of 0.96). In addition, we carried a layer-based immunohistochemical analysis of cervical epithelium, and showed that our method can be used by pathologists to differentiate between different grades of cervical intraepithelial neoplasia by quantitatively assessing the percentage of proliferating cells in the different layers of HPV positive lesions.

Presence of histopathological premalignant lesions and infection caused by high-risk genotypes of human papillomavirus in patients with suspicious cytological and colposcopy results: A prospective study.

In patients with premalignant cervical lesions, human papillomavirus (HPV) infection, at any moment, may be spontaneously eliminated, or may persist or transform cervical epithelium from a lower to a higher degree. Due to that, it is necessary to wisely select the patients who are at high risk of cancer development. The aim of the study was to establish the interdependence between a suspicious Papanicolaou (Pap) test and colposcopy with the infection caused by high-risk genotypes of human papillomavirus and the presence of premalignant cervical lesions.

Patient's specific integration of OAR doses (D2 cc) from EBRT and 3D image-guided brachytherapy for cervical cancer.

The objective of this study was to assess the recommended DVH parameter (e.g., D2 cc) addition method used for combining EBRT and HDR plans, against a reference dataset generated from an EQD2-based DVH addition method. A revised DVH parameter addition method using EBRT DVH parameters derived from each patient's plan was proposed and also compared with the reference dataset. Thirty-one biopsy-proven cervical cancer patients who received EBRT and HDR brachytherapy were retrospectively analyzed. A parametrial and/or paraaortic EBRT boost were clinically performed on 13 patients. Ten IMRT and 21 3DCRT plans were determined. Two different HDR techniques for each HDR plan were analyzed. Overall D2 cc and D0.1 cc OAR doses in EQD2 were statistically analyzed for three different DVH parameter addition methods: a currently recommended method, a proposed revised method, and a reference DVH addition method. The overall D2 ccEQD2 values for all rectum, bladder, and sigmoid for a conformal, volume optimization HDR plan generated using the current DVH parameter addition method were significantly underestimated on average -5 to -8% when compared to the values obtained from the reference DVH addition technique (P < 0.01). The revised DVH parameter addition method did not present statistical differences with the reference technique (P > 0.099). When PM boosts were considered, there was an even greater average underestimation of -8~-10% for overall OAR doses of conformal HDR plans when using the current DVH parameter addition technique as compared to the revised DVH parameter addition. No statistically significant differences were found between the 3DCRT and IMRT techniques (P > 0.3148). It is recommended that the overall D2 cc EBRT doses are obtained from each patient's EBRT plan.

Quality of life assumptions determine which cervical cancer screening strategies are cost-effective.

Quality adjusted life years are used in cost-effectiveness analyses (CEAs). To calculate QALYs, a 'utility' (0-1) is used for each health state induced or prevented by the intervention. We aimed to estimate the impact of quality-of-life (QoL) assumptions (utilities and durations of health states) on CEAs of cervical cancer screening. To do so, twelve alternative sets of utility assumptions were retrieved from published cervical cancer screening CEAs. Two additional sets were based on empirical QoL data that were integrally obtained through two different measures (SF-6D and EQ-5D) from eight groups of women (total n= 3,087), from invitation for screening to diagnosis with cervical cancer. Per utility set we calculated the number of quality-adjusted days lost (QADL) for each relevant health state in cervical cancer screening, by multiplying the study-specific assumed disutilities (i.e. 1-utility) with study-specific durations of the loss in QoL, resulting in 14 'QADL-sets'. With microsimulation model MISCAN we calculated cost-effectiveness of 342 alternative screening programs (varying in primary screening test [Human Papillomavirus (HPV) versus cytology], starting ages, and screening interval) for each of the 14 QADL-sets. Utilities used in CEAs appeared to differ largely. We found that ten QADL-sets from the literature resulted in HPV and two in cytology as preferred primary test. The SF-6D empirical QADL-set resulted in cytology and the EQ-5D one in HPV as preferred primary test. In conclusion, assumed utilities and health state durations determine cost-effectiveness of cervical cancer screening. Also, the measure used to empirically assess utilities can be crucial for CEA conclusions. This article is protected by copyright. All rights reserved.

Piperazine clubbed with 2-azetidinone derivatives suppresses proliferation, migration and induces apoptosis in human cervical cancer HeLa cells through oxidative stress mediated intrinsic mitochondrial pathway.

Piperazine scaffolds or 2-azetidinone pharmacophores have been reported to show anti-cancer activities and apoptosis induction in different types of cancer cells. However, the mechanistic studies involve in induction of apoptosis addressing these two moieties for human cervical cancer cells remain uncertain. The present study emphasizes on the anti-proliferating properties and mechanism involved in induction of apoptosis for these structurally related azoles derivatives in HeLa cancer cells. 1-Phenylpiperazine clubbed with 2-azetidione derivatives (5a-5h) were synthesized, characterized using various spectroscopic techniques and evaluated for their in-vitro anti-proliferative activities and induction of apoptosis. Further, we also evaluated oxidative stress generated by these synthetic derivatives (5a-5h). Cell viability studies revealed that among all, the compound N-(3-chloro-2-(3-nitrophenyl)-4-oxoazetidin-1-yl)-2-(4-phenylpiperazin-1-yl) acetamide 5e remarkably inhibited the growth of HeLa cells in a concentration dependent manner having IC50 value of 29.44 ± 1.46 µg/ml. Morphological changes, colonies suppression and inhibition of migration clearly showed the antineoplasicity in HeLa cells treated with 5e. Simultaneously, phosphatidylserine externalization, DNA fragmentation and cell-cycle arrest showed ongoing apoptosis in the HeLa cancer cells induced by compound 5e in concentration dependent manner. Additionally, generation of intracellular ROS along with the decrease in mitochondrial membrane potential supported that compound 5e caused oxidative stress resulting in apoptosis through mitochondria mediated pathway. Elevation in the level of cytochrome c and upregulation in expression of caspase-3 clearly indicated the involvement of the intrinsic pathway of programmed cell death. In brief; compound 5e could serve as a promising lead for the development of an effective antitumor agent.

Radiation therapy for stage IVA uterine cervical cancer: treatment outcomes including prognostic factors and risk of vesicovaginal and rectovaginal fistulas.

To evaluate the safety and efficacy of radiation therapy for stage IVA uterine cervical cancer and to identify an optimal radiation regimen.

Dosimetric evaluation of image based brachytherapy using tandem ovoid and tandem ring applicators.

The aim of the study is to evaluate the differences in dosimetry between tandem-ovoid and tandem-ring gynaecologic brachytherapy applicators in image based brachytherapy.

The Role of E6 Spliced Isoforms (E6*) in Human Papillomavirus-Induced Carcinogenesis.

Persistent infections with High Risk Human Papillomaviruses (HR-HPVs) are the main cause of cervical cancer development. The E6 and E7 oncoproteins of HR-HPVs are derived from a polycistronic pre-mRNA transcribed from an HPV early promoter. Through alternative splicing, this pre-mRNA produces a variety of E6 spliced transcripts termed E6*. In pre-malignant lesions and HPV-related cancers, different E6/E6* transcriptional patterns have been found, although they have not been clearly associated to cancer development. Moreover, there is a controversy about the participation of E6* proteins in cancer progression. This review addresses the regulation of E6 splicing and the different functions that have been found for E6* proteins, as well as their possible role in HPV-induced carcinogenesis.

Triphenylstannyl((arylimino)methyl)benzoates with selective potency that induce G1 and G2/M cell cycle arrest and trigger apoptosis via ROS in human cervical cancer cells.

Metal complexes with organelle specificity and potent but selective cytotoxicity are highly desirable. A novel series of triphenylstannyl 4-((arylimino)methyl)benzoates (2-8) were obtained by the reactions of triphenylstannyl 4-formylbenzoate [Ph3Sn(L1)] 1 with primary aromatic amines. Two representative compounds (10, 11) were also synthesized by reacting aqua-triphenylstannyl 2-formylbenzoate [Ph3Sn(L9)(H2O)] (9) with aniline and p-fluoroaniline, respectively. These compounds were characterized by elemental analysis, IR and 1H, 13C and 119Sn NMR spectroscopy, as well as single-crystal X-ray diffraction for compounds 5, 7-11 and three pro-ligands. The in vitro cytotoxic activities of 1-11 were assessed using the MTT tetrazolium dye assay against HeLa (human cervical) and MDA-MB-231 (breast) cancer cells, with IC50 values revealing high activity. Compared to cisplatin, compounds 1-11 exhibited enhanced cytotoxic efficacy, indicating their potential as potent anticancer agents. Among these, 1 and 5 demonstrated maximum inhibition in HeLa cells, with negligible effect on normal human embryonic kidney (HEK) cells. The combined results of the DCFH-DA dye and Hoechst 33342/PI nuclear staining assays, along with flow cytometry analysis, show that they possess a dual mode of action: They induced apoptotic cell death, attributable to the tin-assisted generation of reactive oxygen species. Cell cycle analyses indicated that compounds 1 and 5 exhibit cell growth inhibition and may cause turbulences in the G1 and G2/M phases.

Upregulation of the BDNF/TrKB pathway promotes epithelial-mesenchymal transition, as well as the migration and invasion of cervical cancer.

Brain-derived neurotrophic factor (BDNF) has previously been demonstrated to be associated with several types of cancer. In addition, its receptor, tropomyosin related kinase B (TrkB) is involved in tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) is associated with metastasis in cancers. Thus, The aim of the present study was to examine whether BDNF/TrKB expression is linked to a poor survival and the acquisition of the EMT phenotype in cervical cancer. We found that a high positive expression of BDNF/TrKB was associated with poor survival in cervical cancer. Our results revealed that high expression levels of BDNF/TrKB were observed in cervical cancer compared to normal cells. Importantly, we demonstrated that the silencing of TrKB suppressed the activation of EMT via the downregulation of N-cadherin, vimentin, matrix metalloproteinase (MMP)2 and MMP9, and the upregulation of E-cadherin and tissue inhibitor of metalloproteinases (TIMP)2, which resulted in suppressed cell proliferation, migration and invasion. Furthermore, high phosphorylation levels of ERK and Akt were observed in the cervical cancer cells, while these levels were decreased in the cells in which TrKB was knocked down. On the whole, these findings suggest that the BDNF/TrKB pathway is a promising target for the prevention of tumor proliferation, invasion, metastasis and EMT in cervical cancer cells.

Minimally Invasive Esophagectomy with Thoracic Duct Resection Post Neoadjuvant Chemoradiotherapy for Carcinoma Esophagus-Impact on Lymph Node Yield and Hemodynamic Parameters.

Neoadjuvant therapy followed by surgery is the current recommended treatment for locally advanced esophageal carcinoma. Thoracic duct (TD) resection was indicated for radical mediastinal lymphadenectomy. However, TD resection can cause hemodynamic disturbances. The presence of metastasis in TD has not been previously studied.

Eradication of cervical cancer in vivo by an AAV vector that encodes shRNA targeting human papillomavirus type 16 E6/E7.

The major causative agent of cervical cancer is human papilloma virus (HPV); the viral proteins E6 and E7 induce carcinogenesis through the inactivation of the host tumor-suppressor gene. Therefore, the stable expression of specific inhibitors of E6 and E7 in cancer cells is expected to provide effective treatment for cervical cancer without affecting normal tissue. In this study, we propose a novel therapeutic approach using an adeno-associated virus (AAV) vector encoding short hairpin RNA (shRNA) against the oncoproteins E6 and E7 (shE6E7) of HPV type 16 (HPV‑16), termed AAV‑shE6E7. Three different HPV‑16-positive cervical cancer cell lines (BOKU, SiHa and SKG-IIIa cells) were tested for gene transfer efficiency using serotypes of AAV vectors. For in vitro analysis, the cells were transduced AAV‑shE6E7; alternatively, in vivo studies were performed via the administration of a direct injection of AAV‑shE6E7 into cervical cancer cell-derived tumors in mice. The high gene transfer efficiency was observed using AAV2 in all three cervical cancer cell lines. Following transduction, we observed apoptosis, G1 phase arrest and cell growth inhibition. Additionally, in the transduced cells, the E6, E7 and p16 expression levels decreased, whereas the expression levels of p53, p21 and pRb levels were enhanced. The growth of subcutaneously transplanted tumors was markedly inhibited by the single administration of AAV2‑shE6E7, and the tumors were almost completely eradicated without any adverse effects. These results provided evidence of the utility of AAV2‑shE6E7 as a novel treatment approach for cervical cancer.

Synchronous Uterine Metastases from Breast Cancer: Case Study and Literature Review.

Breast cancer rarely metastasizes to the uterus. Here, we report two breast cancer patients with synchronous metastases to the uterus. Case 1 highlights a 46-year-old female with invasive ductal carcinoma who presented with a breast mass and was found to have uterine enlargement on positron emission tomography (PET) scan. Biopsy revealed a metastatic 4 mm focus of breast cancer in the background of endometrial hyperplasia. Case 2 reports a 62-year-old postmenopausal female diagnosed with lobular carcinoma of the breast following an abnormal screening mammogram. A routine pap smear necessitated further workup, revealing simultaneous endometrial and cervical metastasis. Both patients did not have any gynecologic symptoms and presented a diagnostic challenge.

Genistein Promotes Proliferation of Human Cervical Cancer Cells Through Estrogen Receptor-Mediated PI3K/Akt-NF-κB Pathway.

Phytoestrogens are polyphenol compounds which have similar structure to 17β-estradiol (E2), a kind of main estrogen in women. Thus, phytoestrogens may affect the reproductive and endocrine systems, leading to the development of estrogen-related cancers. The effect of genistein (Gen), one of the most studied phytoestrogens, on human cervical cancer cells (HeLa) was investigated in this study. It was found that Gen at concentrations of 0.001, 0.01, 0.1 and 1 µmol·L-1 promoted the proliferation of HeLa cells in a dose-dependent manner. Gen increased the portion of HeLa cells in S phase and decreased the portion of the cells in G1 phase. Besides, apoptosis rate of the cells was significantly lower when treated with Gen compared with the control group. It was also found that the expression of ERα, Akt or nuclear NF-κB p65 protein was activated by Gen. The correlation between these three proteins may be as following: ERα was the upstream, followed by Akt, and then nuclear NF-κB p65 protein. In addition, the downstream genes of activated nuclear NF-κB p65 were found to be associated with cell cycle and apoptosis of cancer cells. Our results suggested that Gen may stimulate cell proliferation partially through the estrogen receptor-mediated PI3K/Akt-NF-κB pathway and the further activation of the downstream genes of nuclear NF-κB p65.

Aleukemic extramedullary T lymphoid/myeloid bilineage hematopoietic and lymphoid malignancy with progression to bilineage leukemia at relapse: A case report.

Bilineage T lymphoid and myeloid (T/My) neoplasms are rare entities among the hematopoietic and lymphoid malignancies. The majority of patients present with leukemic symptoms in which blasts are observed in the peripheral blood (PB) or bone marrow (BM) at a percentage of >20% of nucleated cells. Only a minimal number of cases of T/My bilineage hematopoietic and lymphoid malignancy have been reported with extramedullary infiltration as the initial symptom. The origin of the neoplastic cells in T/My bilineage malignancy has been documented as the hematopoietic stem cells. The present study reports the case of a 31-year-old man with a T/My bilineage malignancy, which initially showed cervical lymph node enlargement beyond the diagnostic criteria of leukemia in the PB and in the BM. Two distinct malignant populations were detected in the cervical lymph node and pleural effusion, one of which was positive for MPO-staining, while the other was positive for cytoplasmic cluster of differentiation 3. Mutations in platelet-derived growth factor receptor α, platelet-derived growth factor receptor β, fibroblast growth factor receptor 1 and other chromosome abnormalities were excluded. The patient obtained complete remission after conventional chemotherapy, but relapsed with bilineage leukemia within a short period of time. Lymphoid and myeloid lineages have been reported to be differentiated from multipotent progenitors asymmetrically. However, the cellular mutation stage in T/My bilineage malignancy remains unclear. The present study also reviews the origin, development and therapeutic strategies for extramedullary T/My bilineage malignancy.

TSLP promotes angiogenesis of human umbilical vein endothelial cells by strengthening the crosstalk between cervical cancer cells and eosinophils.

Our previous study demonstrated that thymic stromal lymphopoietin (TSLP) secreted by cervical cancer cells promotes angiogenesis and recruitment, and regulates the function of eosinophils (EOS). However, the function of TSLP in the crosstalk between EOS and vascular endothelial cells in cancer lesions remains unknown. The aim of the present study was to investigate the effect of EOS caused by TSLP in in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). The results of the present study revealed that recombinant human TSLP protein (rhTSLP) increased the secretion of vascular endothelial growth factor (VEGF), but not fibroblast growth factors, in HL-60-eosinophils (HL-60E). Compared with cervical cancer cells (HeLa or CasKi cells) or HL-60E alone, there were increased levels of interleukin (IL)-8 and VEGF in the co-culture system between cervical cancer cells, and HL-60E cells. This effect was strengthened by rhTSLP, but inhibited by inhibiting the TSLP signal with anti-human TSLP or TSLP receptor neutralizing antibodies. The results of the tube formation assays revealed that treatment with the supernatant from cervical cancer cells and/or HL-60E resulted in an increase in angiogenesis in HUVECs, which could be decreased by TSLP or TSLPR inhibitors. The results of the present study suggested that TSLP derived of cervical cancer cells may indirectly stimulate angiogenesis of HUVECs, by upregulating IL-8 and VEGF production, in a co-culture model between cervical cancer cells and EOS, therefore promoting the development of cervical cancer.

Downregulation of miR-30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer.

Accumulating studies have revealed that microRNAs serve crucial roles in cancer development and progression. MicroRNA-30a (miR-30a) has been implicated in various cancer types. However, the role of miR-30a in cervical cancer remains unclear. In the current study, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay revealed that miR-30a was significantly downregulated in cervical cancer tissues compared with adjacent normal tissues, and in the cervical cancer cell lines HeLa, SiHa and Ca-Ski compared with GH329 normal cervical epithelial cells. A functional assay using miR-30a mimic demonstrated that miR-30a could inhibit the growth and invasion of cervical cancer cells. Additionally, bioinformatics-based prediction and luciferase reporter assays indicated that MEF2D is a direct target of miR-30a. Transfection with miR-30a reduced the mRNA expression and protein levels of MEF2D, as determined using RT-qPCR and western blot analyses. Furthermore, MEF2D expression was negatively correlated with that of miR-30a in cervical cancers. Overall, the present study demonstrated that miR-30a functions as a tumor suppressor by targeting MEF2D in cervical cancer, which may provide the basis for a prognostic biomarker or therapeutic strategy for cervical cancer.

Expression and clinical significance of programmed death-1 on lymphocytes and programmed death ligand-1 on monocytes in the peripheral blood of patients with cervical cancer.

The programmed death-1 (PD-1) signaling pathway serves a critical role in immune regulation and tolerance by suppressing the activation and proliferation of T cells. The aim of the present study was to investigate the effect of PD-1 and programmed death-ligand 1 (PD-L1) on the development of cervical carcinoma and cervical intraepithelial neoplasia (CIN). A total of 40 healthy controls (HC), 40 patients with CIN and 66 newly diagnosed cervical cancer patients were recruited. The expression level of PD-1 expression on peripheral cluster of differentiation (CD)4+ and CD8+ T cells and PD-L1 on monocytes was analyzed by flow cytometry. The expression level of soluble PD-L1 in serum was determined by an ELISA. The results of the present study demonstrated that the PD-1 expression level on CD4+ and CD8+ T cells was significantly increased in CIN and cervical cancer, compared with that in HC. In addition, the PD-1 expression level on CD4+ and CD8+ T cells was increased in cervical cancer, compared with that in CIN. However, the expression level of PDL-1 on CD14+ monocytes was increased in cancer and CIN, but limited in cancer and CIN. In addition, PD-1 expression on CD4+ T cells was positively associated with PD-1 expression on CD8+ T cells in cervical cancer (P<0.05). Further analyses revealed that the proportion of PD-1 on CD4+ and CD8+ T cells were positively associated with tumor stages. However, no difference in the degree of soluble PD-1 among cancer, CIN and HC cells was revealed. The results suggested that the PD-1 signaling pathway is involved in the development of CIN and cervical cancer.

Clinical outcome of extended-field irradiation vs. pelvic irradiation using intensity-modulated radiotherapy for cervical cancer.

The aim of the present study was to evaluate the distinctions in survival and toxicity between patients with cervical cancer with common iliac node or para-aortic node involvement, who were treated with extended-field intensity-modulated radiotherapy (EF-IMRT) and patients with or without lower involved pelvic nodes, who were treated with pelvic IMRT. A total of 55 patients treated with EF-IMRT and 52 patients treated with pelvic IMRT at the Sun Yat-Sen University Cancer Center (Guangzhou, China) were retrospectively analyzed. Patients treated with EF-IMRT had the highest level of lymph node involvement to the para-aortic or common iliac nodes, while patients treated with pelvic IMRT had no para-aortic or common iliac nodes involved (P<0.001). The median follow-up time was 29.5 months. The 3-year overall survival (OS) rates of EF-IMRT and pelvic IMRT were 79.4 and 82.3% (P=0.45), respectively, and the 3-year disease-free survival (DFS) rates of EF-IMRT and pelvic IMRT were 61.0 and 73.7% (P=0.55), respectively. Cox's regression analysis revealed that EF irradiation was a protective prognostic factor for OS and DFS. A total of 16 patients in the EF-IMRT group and 13 patients in the pelvic IMRT group experienced treatment failure (P=0.67), with the patterns of failure being the same for the two groups (P=0.88). The cumulative incidence of grade 3 and 4 acute toxicities in the EF-IMRT group was 34.5%, in comparison with 19.2% in the pelvic group (P=0.048). The results of the present study suggest that patients with cervical cancer with grossly involved common iliac or para-aortic nodes should be electively subjected to EF irradiation to improve the survival and alter patterns of recurrence. Notably, EF irradiation delivered via IMRT exhibits an increased toxicity incidence, however, this remains within an acceptable range.

A novel microRNA, hsa-miR-6852 differentially regulated by Interleukin-27 induces necrosis in cervical cancer cells by downregulating the FoxM1 expression.

We have previously demonstrated that Interleukin-27 differentially regulates the expression of seven novel microRNAs. Here we elucidate the functional significance of these novel microRNAs. Of the seven microRNAs, over expression of miRNA-6852 (miR-SX4) mimic induces cell cycle arrest at G2/M phase and induces necrosis in HEK293 and panel of cervical cancer cells (Human Papilloma Virus (HPV) infected cell lines; HeLa, CaSki and SiHa cells). To define the mechanism of the miR-SX4-mediated G2/M arrest, a microarray gene chip array and western blot analysis were performed. FoxM1, a transcription factor is identified as a key protein down-regulated by miR-SX4, even though the miR-SX4 does not target 3'UTR of FoxM1. Knock down of FoxM1 using si-RNA demonstrate that FoxM1 silenced cell induces G2/M cell cycle arrest and necrosis. Our data demonstrated for the first time that miR-SX4 could be a potent anti-cancer microRNA.

Knowledge of cervical cancer and Pap smear among Uyghur women from Xinjiang, China.

Cervical cancer is a significant public health issue in Xinjiang China. In order to provide scientific basis for cervical cancer intervention in Xinjiang, women's knowledge of cervical cancer was investigated in this study. Besides, relations between Uyghur women's awareness and their age, educational background, yearly household were evaluated.

A Network Meta-Analysis on the Diagnostic Value of Different Imaging Methods for Lymph Node Metastases in Patients With Cervical Cancer.

We performed this network meta-analysis to compare the diagnostic value of 4 imaging methods (magnetic resonance imaging, positron emission tomography, computed tomography, and diffusion-weighted imaging) for diagnosing lymph node metastases in cervical cancer.

Intrinsic fluorescence for cervical precancer detection using polarized light based in-house fabricated portable device.

An in-house fabricated portable device has been tested to detect cervical precancer through the intrinsic fluorescence from human cervix of the whole uterus in a clinical setting. A previously validated technique based on simultaneously acquired polarized fluorescence and polarized elastic scattering spectra from a turbid medium is used to extract the intrinsic fluorescence. Using a diode laser at 405 nm, intrinsic fluorescence of flavin adenine dinucleotide, which is the dominant fluorophore and other contributing fluorophores in the epithelium of cervical tissue, has been extracted. Different grades of cervical precancer (cervical intraepithelial neoplasia; CIN) have been discriminated using principal component analysis-based Mahalanobis distance and linear discriminant analysis. Normal, CIN I and CIN II samples have been discriminated from one another with high sensitivity and specificity at 95% confidence level. This ex vivo study with cervix of whole uterus samples immediately after hysterectomy in a clinical environment indicates that the in-house fabricated portable device has the potential to be used as a screening tool for in vivo precancer detection using intrinsic fluorescence.

Stability, integrity, and recovery rate of cellular nucleic acids preserved in a new liquid-based cytology medium.

Liquid-based cytology (LBC) has replaced the conventional Papanicolaou test in cervical cancer screening. The cervical swab specimens collected in LBC media can also be used for additional analyses including high-risk HPV (HR-HPV) test, DNA methylation analysis, and HPV E6/E7 mRNA test.

Clinical outcomes of carbon ion radiotherapy with concurrent chemotherapy for locally advanced uterine cervical adenocarcinoma in a phase 1/2 clinical trial (Protocol 1001).

We conducted a phase 1/2 study to evaluate the efficacy and safety of carbon ion radiotherapy (C-ion RT) with concurrent chemotherapy for locally advanced uterine cervical adenocarcinoma. Thirty-three patients were enrolled between April 2010 and March 2014. Treatment consisted of C-ion RT with concurrent weekly cisplatin at a dose of 40 mg/m2 . In the phase 1 component, the total dose was escalated from 68.0 Gy (relative biological effectiveness [RBE]) to 74.4 Gy (RBE) to determine the maximum tolerated dose of C-ion RT. In the phase 2 component, the efficacy and safety of C-ion RT with concurrent chemotherapy were evaluated using the dose determined in the phase 1 component. The median follow-up duration was 30 months. Two patients did not receive chemotherapy because of anemia or leukocytopenia immediately prior to commencing treatment; 31 patients were analyzed. None of the patients developed dose-limiting toxicities. The recommended dose (RD) was determined to be 74.4 Gy (RBE). In the phase 2 component, two patients developed Grade 3-4 toxicities in the gastrointestinal tract, due to repeated laser coagulation or peritonitis caused by appendicitis. In the patients treated with the RD, the 2-year local control, progression-free survival, and overall survival rates were 71%, 56%, and 88%, respectively. C-ion RT with concurrent weekly cisplatin was well tolerated in patients with locally advanced uterine cervical adenocarcinoma. Our findings support further investigations into the efficacy of this strategy.

Eurogin Roadmap 2017: Triage strategies for the management of HPV-positive women in cervical screening programmes.

Cervical cancer screening will rely, increasingly, on HPV testing as a primary screen. The requirement for triage tests which can delineate clinically significant infection is thus prescient. In this EUROGIN 2017 roadmap, justification behind the most evidenced triages is outlined, as are challenges for implementation. Cytology is the triage with the most follow-up data; the existence of an HR-HPV positive, cytology negative group presents a challenge and re-testing intervals for this group (and choice of re-test) require careful consideration. Furthermore, cytology relies on subjective skills and while adjunctive dual-staining with p16/Ki67 can mitigate inter-operator/site disparities, clinician-taken samples are required. Comparatively, genotyping and methylation markers are objective and are applicable to self-taken samples, offering logistical advantages including in low and middle income settings. However, genotyping may have diminishing returns in immunised populations and type(s) included must balance absolute risk for disease to avoid low specificity. While viral and cellular methylation markers show promise, more prospective data are needed in addition to refinements in automation. Looking forward, systems that detect multiple targets concurrently such as next generation sequencing platforms will inform the development of triage tools. Multi-step triage strategies may be beneficial provided they do not create complex, unmanageable pathways. Inevitably, the balance of risk to cost(s) will be key in decision making, although defining an acceptable risk will likely differ between settings. Finally, given the significant changes to cervical screening and the variety of triage strategies, appropriate education of both health care providers and the public is essential. This article is protected by copyright. All rights reserved.

Screening program for cervical cancer: public policies and experiences of actors who implement the program in the state of Veracruz, Mexico.

The aim of this article is to analyze the way in which the Screening Program for Cervical Cancer is carried out in a dysplasia clinic and related health centers in the state of Veracruz, through the representations and practices of the social actors who implement the program. In order to do so, in-depth interviews and observations of the practices of health service providers were carried out during different periods over the course of three years, from 2009 to 2011. Through the information obtained, the article explores the difficulties, achievements and results of this program as part of a public policy. Although a priority of public health policy is to see the whole population benefit from preventive and curative health care services, evidence shows that marginalized populations are not benefitted by such programs; such information does not however seem to permeate popular and medical knowledge.

Vaccination and Health Maintenance Issues to Consider in Patients With Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) do not receive routine preventive care at the same rate as the general population. IBD places patients at increased risk for developing vaccine-preventable illnesses. This risk is further exacerbated by immunosuppressive therapy. This article highlights the necessary vaccinations for IBD patients and the timing of vaccination for immunosuppressed patients, and discusses the health maintenance needs and preventive care issues related to heart disease, smoking, osteoporosis, mental health, cervical cancer, and skin cancer.

Radio-resistant Cervical Cancers Are Sensitive to Inhibition of Glycolysis and Redox Metabolism.

Highly glycolytic cervical cancers largely resist treatment by cisplatin and co-administered pelvic irradiation as the present standard of care. In this study, we investigated the effects of inhibiting glycolysis and thiol redox metabolism to evaluate them as alternate treatment strategies in these cancers. In a panel of multiple cervical cancer cell lines, we evaluated sensitivity to inhibition of glycolysis (2-DG) with or without simultaneous inhibition of glutathione and thioredoxin metabolism (BSO/AUR). Intracellular levels of total and oxidized glutathione, thioredoxin reductase activity, and indirect measures of intracellular reactive oxygen species (ROS) were compared before and after treatment. Highly radio-resistant cells were the most sensitive to 2-DG, whereas intermediate radio-resistant cells were sensitive to 2-DG plus BSO/AUR. In response to 2-DG/BSO/AUR treatment, we observed increased levels of intracellular oxidized glutatione, redox-sensitive dye oxidation and decreased glucose utilization via multiple metabolic pathways including the TCA cycle. 2-DG/BSO/AUR treatment delayed the growth of tumors composed of intermediate radio-resistant cells and effectively radio-sensitized these tumors at clinically relevant radiation doses both in vitro and in vivo. Overall, our results support inhibition of glycolysis and intracellular redox metabolism as an effective alternative drug strategy for the treatment of highly glycolytic and radio-resistant cervical cancers.

E6 protein expressed by high-risk HPV activates super-enhancers of the EGFR and c-MET oncogenes by destabilizing the histone demethylase KDM5C.

The high-risk (HR) human papillomaviruses (HPV) are causative agents of anogenital tract dysplasia and cancers and a fraction of head and neck cancers. The HR HPV E6 oncoprotein possesses canonical oncogenic functions, such as p53 degradation and telomerase activation. It is also capable of stimulating expression of several oncogenes, but the molecular mechanism underlying these events are poorly understood. Here we provide evidence that HPV16 E6 physically interacts with histone H3K4 demethylase KDM5C, resulting in its degradation in an E3 ligase E6AP- and proteasome-dependent manner. Moreover, we found that HPV16-positive cancer cell lines exhibited lower KDM5C protein levels than HPV-negative cancer cell lines. Restoration of KDM5C significantly suppressed the tumorigenicity of CaSki cells, an HPV16-positive cervical cancer cell line. Whole genome ChIP-seq and RNA-seq results revealed that CaSki cells contained super-enhancers in the proto-oncogenes EGFR and c-MET. Ectopic KDM5C dampened these super-enhancers and reduced the expression of proto-oncogenes. This effect was likely mediated by modulating H3K4me3/H3K4me1 dynamics and decreasing bi-directional eRNA transcription. Depletion of KDM5C or HPV-16 E6 expression activated these two super-enhancers. These results illuminate a pivotal relationship between the oncogenic E6 proteins expressed by high-risk HPV isotypes and epigenetic activation of super-enhancers in the genome that drive expression of key oncogenes like EGFR and c-MET.