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Background: Studies comparing the anastomotic leak rate in patients with an intrathoracic versus a cervical anastomosis after oesophagectomy are equivocal. The aim of this study was to compare clinical outcome after oesophagectomy in patients with an intrathoracic or cervical anastomosis, and to identify predictors of anastomotic leakage in a nationwide audit. Methods: Between January 2011 and December 2015, all consecutive patients who underwent oesophagectomy for cancer were identified from the Dutch Upper Gastrointestinal Cancer Audit. For the comparison between an intrathoracic and cervical anastomosis, propensity score matching was used to adjust for potential confounders. Multivariable logistic regression modelling with backward stepwise selection was used to determine independent predictors of anastomotic leakage. Results: Some 3348 patients were included. After propensity score matching, 654 patients were included in both the cervical and intrathoracic anastomosis groups. An intrathoracic anastomosis was associated with a lower leak rate than a cervical anastomosis (17·0 versus 21·9 per cent; P = 0·025). The percentage of patients with recurrent nerve paresis was also lower (0·6 versus 7·0 per cent; P < 0·001) and an intrathoracic anastomosis was associated with a shorter median hospital stay (12 versus 14 days; P = 0·001). Multivariable analysis revealed that ASA fitness grade III or higher, chronic obstructive pulmonary disease, cardiac arrhythmia, diabetes mellitus and proximal oesophageal tumours were independent predictors of anastomotic leakage. Conclusion: An intrathoracic oesophagogastric anastomosis was associated with a lower anastomotic leak rate, lower rate of recurrent nerve paresis and a shorter hospital stay. Risk factors for anastomotic leak were co‐morbidities and proximal tumours. [ABSTRACT FROM AUTHOR]

Objective: To establish a real‐time predictive scoring model based on sonographic characteristics for identifying malignant cervical lymph nodes (LNs) in cancer patients after neck irradiation. Methods: One‐hundred forty‐four irradiation‐treated patients underwent ultrasonography and ultrasound‐guided fine‐needle aspirations (USgFNAs), and the resultant data were used to construct a real‐time and computerised predictive scoring model. This scoring system was further compared with our previously proposed prediction model. Results: A predictive scoring model, 1.35 × (L axis) + 2.03 × (S axis) + 2.27 × (margin) + 1.48 × (echogenic hilum) + 3.7, was generated by stepwise multivariate logistic regression analysis. Neck LNs were considered to be malignant when the score was ≥ 7, corresponding to a sensitivity of 85.5%, specificity of 79.4%, positive predictive value (PPV) of 82.3%, negative predictive value (NPV) of 83.1%, and overall accuracy of 82.6%. When this new model and the original model were compared, the areas under the receiver operating characteristic curve (c‐statistic) were 0.89 and 0.81, respectively (P < .05). Conclusions: A real‐time sonographic predictive scoring model was constructed to provide prompt and reliable guidance for USgFNA biopsies to manage cervical LNs after neck irradiation. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the most common gynecological malignancies. Mousasi 2 (Msi2) is a RNA-binding protein that regulates various key cellular functions and has emerged as a crucial regulator of cancer development. However, the clinical significance and biological functions of Msi2 in cervical cancer remain unknown. The current study assessed the expression of Msi2 mRNA using reverse transcription-quantitative polymerase chain reaction. Furthermore, the expression of Msi2 was examined in 162 cervical cancer samples using immunohistochemistry and the association between Msi2 expression and patient clinicopathological features was analyzed. The overall survival (OS) and progression-free survival (PFS) of patients were estimated using the Kaplan-Meier method and Cox regression analysis was performed to investigate the clinicopathological significance of Msi2 expression. In vitro migration and invasion assays were performed in Sinha and Caskie cells. The results demonstrated that, compared with normal cervical tissues, the expression of Msi2 was increased in cervical cancer tissues. The expression of Msi2 was significantly correlated with International Federation of Gynaecology and Obstetrics (FIGO) stage (P=0.049) and lymph node metastasis (P=0.036). Furthermore, patients with higher Msi2 expression exhibited significantly poorer OS (P=0.013) and PFS (P=0.006) than patients with low Msi2 expression. Notably, high Msi2 expression was correlated with poorer OS in patients with a FIGO stage ≤I (P=0.015), a smaller tumor size (P=0.043) and grade 3 tumor (P=0.002). High Msi2 expression was also correlated with a poorer PFS in patients with a FIGO stage ≤I (P=0.016) and grade 3 tumor (P=0.001). Multivariate analysis suggested that Msi2 expression was an independent prognostic marker of the OS (P=0.027) and PFS (P=0.013) of patients with cervical cancer. Furthermore, Msi2 knockdown significantly (P<0.05) inhibited the invasion and migration of cervical cancer cells. The results of the current study demonstrate that Msi2 may act as a prognostic biomarker in patients with cervical cancer. Targeting Msi2 may therefore offer a promising therapeutic strategy for the treatment of patients with cervical cancer. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study is to determine the quality of life by functional assessment, cancer related fatigue and describe the lived experiences of cervical cancer patients undergoing sensitization chemotherapy in a tertiary referral hospital. Background: Patients diagnosed with cancer at an advanced stage of the disease and receiving sensitization chemotherapy experience a variety of psychosocial problems in addition to their physical problems. Women with cervical cancer are more vulnerable to experience loss of functional wellbeing and thereby have poor quality of life. They also experience cancer related fatigue along with a variety of other physical symptoms and psychological problems when compared to other patients. Exploration of lived experiences of these women who have poor quality of life may help in providing a deeper understanding on the issues these women face day in and day out. Design: Mixed method; (Sequential exploratory design). Method: The study comprises of two phases: (i) Quantitative phase: to determine the functional assessment- quality of life and cancer related fatigue in women with cervical cancer who are currently receiving sensitization chemotherapy; (ii) Qualitative phase: will adopt a nested sampling technique, for choosing women with cervical cancer with poor quality of life. The objective will be to describe the lived experiences of women with cervical cancer on sensitization chemotherapy. Qualitative data will be collected using an unstructured interview guide. Conclusion: This study will help to provide information on the quality of life and cancer related fatigue of women with cervical cancer on sensitization chemotherapy. This study would further help in exploring the lived experiences of women with poor quality of life. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play important roles in the carcinogenesis of cervical cancer. However, the expression and underlying mechanisms of miRNA in cervical cancer progression remain unclear. In the present study, our data showed that the expression of miR-138-5p was significantly downregulated in cervical cancer tissues, and decreased expression of miR-138-5p was correlated with advanced FIGO stage, poor differentiation, lymph node metastasis, and poor overall survival of cervical cancer patients. Function assays showed that overexpression of miR-138-5p reduced cervical cancer cell proliferation, arrested cells in the G0/G1 phase, and induced cell apoptosis in vitro. Remarkably, SIRT1 was confirmed as a direct target of miR-138-5p in cervical cancer, and miR-138-5p exerted the reduced tumor functions by suppressing SIRT1 expression. Moreover, we further identified that lncRNA H19 could act as a molecular sponge of miR-138-5p in cervical cancer progression. Taken together, these results suggested that miR-138-5p could suppress cervical cancer cell progression by targeting SIRT1. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to find the potential miRNA expression signature capable of predicting survival time for cervical squamous cell carcinoma (CSCC) patients. Methods: The expression of 332 miRNAs was measured in 131 (Training cohort) and 130 (Validation cohort) patients with CSCC in the Cancer Genome Atlas (TCGA) data portal. The miRNA expression signature was identified by Cox Proportion Hazard regression model to the Training data set, and subsequently validated in an independent Validation set. Kaplan-Meier curves and the receiver operating characteristic analyses of 5 years were used to access the overall survival of miRNA signature. MiRNA signature-gene target analysis was performed, followed by the construction of the regulatory network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to explore the function of target genes of miRNA signature. Results: A 2-miRNA expression signature of hsa-mir-642a and hsa-mir-378c associated with survivability was identified in CSCC. Both of them had a significant diagnostic and prognostic value of patients with CSCC. A total of 345 miRNA signature-target pairs were obtained in the miRNA signature-gene target regulatory network, in which 316 genes were targets of has-mir-378c and has-mir-642a. Functional analysis of target genes showed that MAPK signaling pathway, VEGF signaling pathway and endocytosis were the significantly enriched signal pathways that covered most genes. Conclusions: The 2-miRNA signature adds to the prognostic value of CSCC. In-depth interrogation of the 2-miRNAs will provide important biological insights that finding and developing novel molecularly prediction to improve prognosis for CSCC patients. [ABSTRACT FROM AUTHOR]

Objective: The Japan Society of Gynecologic Oncology (JSGO) initiated a nation-wide training system for the education and certification for gynecologic oncologists in 2005. To assess the impact of the quality of the JSGO-accredited institutions, JSGO undertook an analysis of the Uterine Cervical Cancer Registry of the Japan Society of Obstetrics and Gynecology (JSOG) to determine the effectiveness of the JSGO-accredited institutions on the treatment and survival of women with cervical cancer. Methods: The effectiveness of 119 JSGO-accredited institutions and 125 non-JSGO-accredited institutions on the treatment and survival of women with cervical cancer were compared by analyzing the tumor characteristics, treatment patterns, and survival outcomes of women with stage T1B-T4 cervical cancer utilizing the data in the JSOG nation-wide registry for cervical cancer (2006-2009). Results: A total of 14,185 eligible women were identified: 10,920 (77.0%) cases for 119 JSGO-accredited institutions and 3,265 (23.0%) cases for 125 non-accredited institutions. A multivariate analysis showed that age, stage, histology type, and treatment pattern were independently associated with mortality. Moreover, women who received treatment at the JSGO-accredited institutions had a significantly decreased mortality risk compared to non-accredited institutions (adjusted hazard ratio [aHR]=0.843; 95% confidence interval [CI]=0.784-0.905). Similar findings on multivariate analysis were seen among subset of women who received surgery alone (aHR=0.552; 95% CI=0.393-0.775) and among women who received radiotherapy (aHR=0.845; 95% CI=0.766-0.931). Conclusion: Successful implementation of gynecologic oncology accrediting institution was associated with improved survival outcome of women with cervical cancer in Japan. [ABSTRACT FROM AUTHOR]

Objective: To examine trends and characteristics of single women with malignancy of the uterine cervix. Methods: This is a retrospective observational study examining the United States populationbased tumor registry (the Surveillance, Epidemiology, and End Results program). Time-specific trends in single marital status were examined in 3,294,208 women among 12 common female malignancies including 87,151 women with uterine cervical malignancy between 1973 and 2013. Results: While the proportion of single women in the majority of malignancies increased during the study time, the proportion of single women with cervical malignancy significantly increased more than in other malignancies (29.3% in 2013 from 6.3% in 1973). There was a surge in the proportion of single women with cervical malignancy starting in the early 1990s, exhibiting the largest annual percentage rate change (APC) among all examined malignancies (1.8%; 95% confidence interval [CI]=1.6, 2.0; p<0.001). There was a significant decrease in the proportion of women aged <40 years with cervical malignancy between 1989 and 2013 (APC, -1.2%; 95% CI=-1.4, -1.0; p<0.001). However, when stratified by age, the proportion of single women aged ≥40 years increased significantly during the time (APC, 2.7%; 95% CI=2.3, 3.2; p<0.001) but did not in those who were <40 years (APC, 0.1%; 95% CI=-0.7, 0.6; p=0.850). Conclusion: The proportion of single women with malignancy of the uterine cervix has significantly increased in the past 4 decades. This increase was most dramatic in single women aged ≥40 years. Improving screening strategies in single women aged ≥40 years may help reduce the incidence of this malignancy. [ABSTRACT FROM AUTHOR]

Objective: Few data exist regarding adjuvant hysterectomy (AH) in locally advanced cervical cancer (LACC) patients treated with chemoradiotherapy. We investigated the effect of AH on prognosis in LACC patients, through meta-analysis. Methods: EMBASE and MEDLINE databases and the Cochrane Library were searched for published studies comparing LACC patients who received AH after chemoradiotherapy with those who did not, through April 2016. Endpoints were mortality and recurrence rates. For pooled estimates of the effect of AH on mortality/recurrence, random-or fixed-effects metaanalytical models were used. Results: Two randomized trials and six observational studies (AH following chemoradiotherapy, 630 patients; chemoradiotherapy, 585 patients) met our search criteria. Fixed-effects model-based meta-analysis indicated no significant difference in mortality between the groups (odds ratio [OR]=1.01; 95% confidence interval [CI]=0.58-1.78; p=0.968) with low cross-study heterogeneity (p=0.73 and I2=0.0). This pattern was observed in subgroup analysis for study design, radiation type, response after chemoradiotherapy, and hysterectomy type. The pooled OR for AH and recurrence was 0.59 (95% CI=0.44-0.79; p<0.05) with low cross-study heterogeneity (p=0.29 and I2=17.8), favoring the AH group. However, this pattern was not observed in the subgroup analysis for the randomized trials. There was no evidence of publication bias. Conclusion: In this meta-analysis, AH following chemoradiotherapy did not improve survival in patients with LACC, although it seemed to reduce the risk of recurrence. Concerning the significant morbidity of AH after chemoradiotherapy, routine use of AH should be avoided. [ABSTRACT FROM AUTHOR]

Background: In developed countries, women attend follow-up after treatment for cervical cancer to detect recurrence. The aim of this study was to describe the Danish population of women with early-stage cervical cancer at risk for recurrence and death due to recurrence.Methods: Data were extracted from 3 nationwide databases to find women diagnosed with stage 1A1 to 1B1 cervical cancer in 2005-2013. Recurrences were determined from data on oncological or surgical treatment more than 3 months after the initial diagnosis and were cross-checked with patient journals.Results: In all, 1523 patients were diagnosed with stage 1A1 to 1B1 cervical cancer. Eighty women experienced recurrences: 8 at International Federation of Gynecology and Obstetrics (FIGO) stage 1A1, 0 at FIGO stage 1A2, and 72 at FIGO stage 1B1. The 5-year recurrence rate was 6.4%; 67.5% of the women had symptomatic recurrences, and 28.8% had asymptomatic recurrences. At significantly greater risk for recurrence were women at stage 1B1, regardless of their lymph node (LN) status at diagnosis (hazard ratio with a positive LN, 5.10; 95% confidence interval [CI], 1.65-15.76; P = .0047; hazard ratio with a negative LN, 3.14; 95% CI, 1.25-7.93; P = .0153; hazard ratio with LN data missing, 6.33; 95% CI, 1.80-22.26; P = .004), women older than 50 years (hazard ratio, 1.81; 95% CI, 1.12-2.94; P = .0158), and women with lymphatic and lymphovascular space invasion (LVSI; hazard ratio, 1.92; 95% CI, 1.11-3.30; P = .0188). In a multivariate analysis, significantly inferior survival was found after recurrence for patients with lymphatic LVSI (hazard ratio, 2.23; 95% CI, 1.04-4.80; P = .0401), a symptomatic diagnosis of recurrence (hazard ratio, 2.52; 95% CI, 1.08-5.90; P = .0332), and multiple sites of recurrence (hazard ratio, 2.72; 95% CI, 1.32-5.61; P = .0066).Conclusions: This study has identified a group of women at FIGO stage 1A1 in no need of specialized, hospital-based follow-up. Many of the recurrences at FIGO stage 1B1 are asymptomatic, and this may show a need for follow-up in this group. Further prospective investigation is needed. Cancer 2018;124:943-51. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Introduction. The Cervical Cancer (CC) Prevention Programme includes 3 phases: basic (Pap smear collection), diagnostic (Pap smear evaluation) and in-depth (colposcopy/biopsy in case of abnormal smear test findings). The Programme service providers are subject to an external audit and this publication's objective is to analyse its results from 2016 and the first half of 2017. Materials and methods. The audit of the Programme performance in the period 01.01.2016-30.06.2017 was carried out by external auditors by way of personal visits to the offices of the service providers and by way of direct data retrieval. The audit covered 12% (198) of the basic phase, 100% (66) of the diagnostic phase and 100% (62) of the in-depth phase facilities. The Polish National Health Fund (NHF) did not make available the routinely collected data for the purpose of audit. Audit data collected in the developed protocols were analysed. Results. The number of Pap smears (2,028,988) and the number of colposcopies (13,636) outside the Programme was, respectively, more than two and three times higher than in the Programme (cytology — 801,640, colposcopy — 3929). The performance of the procedures (Programme vs outside the Programme) was highly variable depending on the provider. The percentage of Pap smears unsuitable for evaluation did not differ significantly between gynaecologists and midwives. All audited cytological laboratories carried out rescreening of samples. Biopsy was not performed in 11% (2016) and 15% (2017) of colposcopy laboratories. Inaccuracies were found in 19% (61) of the audit protocols. Discussion. Significantly higher number of procedures performed outside the Programme results from lower renumeration of procedures within the Programme. Variable provider's preferences in the mode of procedures execution indicates that with the use of appropriate organisational solutions it would be possible to reduce opportunistic screening, which is of unknown quality. The quality of Pap smear sample collection in the case of gynaecologists and midwives is the same, but the number of primary care provider (PCP) facilities where midwives collect smears is very limited. The inaccuracies noted in the audit protocols indicate that the lack of access to data collected by the National Health Fund decreased the quality of the audit carried out and the reliability of the data obtained. Conclusions. Restoring full access to data collected by the NHF is crucial for the Programme audit quality. Measures should be implemented to reduce opportunistic screening and shift the stream of tests to the Programme (both at the basic and at the in-depth phase), and to increase the availability of tests in PCP facilities through training for midwives. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the long-term disease control and toxicity to the organs at risk after dose-escalated image-based adaptive brachytherapy (BT) in cervical cancer. Methods and Materials Sixty patients of cervical cancer were treated with external radiotherapy 46 Gy in 23 fractions with weekly cisplatin and MRI-guided BT 7 Gy × 4 fractions with a minimum dose of 85.7 Gy (EQD2) to the high-risk clinical target volume (HRCTV). The BT dose was initially prescribed to point A and plans were optimized to ensure coverage of both point A and HRCTV while maintaining doses to the organs at risk within the recommended constraints. Patients were followed up clinically every three months for the first two years and six months thereafter. Toxicity scoring for urinary and bowel symptoms was done using CTCAE version 3.0. Results The mean doses to the point A and D90 HRCTV were 85.5 (±2.75) Gy and 98.4 (±9.6) Gy EQD2 respectively. The mean 2 cc EQD2, the bladder, rectum, and sigmoid were 90.6 Gy, 70.2 Gy, and 74.2 Gy respectively. The overall survival at a median followup of 49.8 months was 91.66%. Six (10%) patients developed grade 3 gastrointestinal toxicity. One patient developed grade 3 bladder toxicity. The incidence of bladder, rectal, and sigmoid toxicity increased significantly with doses >85 Gy, 66 Gy, and >71 Gy EQD2 respectively. Conclusions While the incidence of grade 3-4 toxicity was low (8.3% for gastrointestinal toxicity and 1.6% for bladder), the threshold for development of grade 1-2 bladder and rectal toxicity was lower than the doses recommended by the GEC-ESTRO group. By adhering to volume-based prescriptions, there is scope of further reduction in toxicity to organs at risk. [ABSTRACT FROM AUTHOR]

Purpose To study the dosimetric impact of deformable image registration–based contour propagation on MRI-based cervical cancer brachytherapy planning. Methods and Materials High-risk clinical target volume (HRCTV) and organ-at-risk (OAR) contours were delineated on MR images of 10 patients who underwent ring and tandem brachytherapy. A second set of contours were propagated using a commercially available deformable registration algorithm. “Manual-contour” and “propagated-contour” plans were optimized to achieve a maximum dose to the most minimally exposed 90% of the volume ( D 90 ) (%) of 6 Gy/fraction, respecting minimum dose to the most exposed 2cc of the volume ( D 2cc ) OAR constraints of 5.25 Gy and 4.2 Gy/fraction for bladder and rectum/sigmoid (86.5 and 73.4 Gy equivalent dose in 2 Gy fractions [EQD 2 ] for external beam radiotherapy [EBRT] + brachytherapy, respectively). Plans were compared using geometric and dosimetric (total dose [EQD 2 ] EBRT + brachytherapy) parameters. Results The differences between the manual- and propagated-contour plans with respect to the HRCTV D 90 and bladder, rectum, and sigmoid D 2cc were not statistically significant (per-fraction basis). For the EBRT + brachytherapy course, the D 2cc delivered to the manually contoured OARs by the propagated-contour plans ranging 98–107%, 95–105%, and 92–108% of the dose delivered by the manual-contour plans (max 90.4, 70.3, and 75.4 Gy for the bladder, rectum, and sigmoid, respectively). The HRCTV dose in the propagated-contour plans was 97–103% of the dose in the manual-contour plans (maximum difference 2.92 Gy). Increased bladder filling resulted in increased bladder dose in manual- and propagated-contour plans. Conclusions When deformable image registration–propagated contours are used for cervical brachytherapy planning, the HRCTV dose is similar to the dose delivered by manual-contour plans and the doses delivered to the OARs are clinically acceptable, suggesting that our algorithm can replace manual contouring for appropriately selected cases that lack major interfractional anatomical changes. [ABSTRACT FROM AUTHOR]

Purpose Given the limited data using an interstitial approach with 3D-based planning for definitive cervical cancer utilizing the GEC-ESTRO defined high-risk clinical target volume (HR-CTV), we reviewed our institutional experience of cervical cancer patients with HR-CTVs ≥ 30 cc to determine whether our clinical and toxicity outcomes are acceptable. Methods A retrospective review of 37 cervical cancer patients with high-risk clinical target volumes (HR-CTVs) ≥30 cc treated with interstitial image-guided brachytherapy (IS IGBT) was performed. All patients received external beam radiotherapy to a median dose of 45 Gy, followed by IS IGBT delivered in a single implant to a median dose of 6 Gy × 5 fractions. Median HR-CTV was 59 cc. A median HR-CTV D 90 of 87.44 Gy was achieved. Kaplan–Meier method was used to evaluate local control (LC), distant control, and overall survival (OS), with stratification by overall treatment time (OTT) ≤ 7 or >7 weeks. Results Median followup was 17 months. The estimated 2-year LC, distant control, and OS were 77.6% (confidence interval [CI]: 63.8–94.5%), 56.8% (CI: 41.3–78.1%), and 54.4% (CI: 39.4–75%), respectively. The 2-year LC for OTT ≤7 weeks and >7 weeks were 100% and 58.3%, respectively ( p = 0.026). The 2-year OS for OTT ≤7 weeks and >7 weeks were 77.8% and 38%, respectively ( p = 0.021). Discussions IS IGBT can achieve a high D 90 to the HR-CTV even in the setting of large-volume disease and results in a favorable LC and toxicity profile. OTT > 7 weeks is associated with significant decrease in LC and OS. Conclusions Efforts should be made to complete whole treatment within 7 weeks as this is associated with improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Background and purpose To analyse the clinical use of needles and examine the feasibility to meet the planning criteria in three fractions of cervical cancer brachytherapy. Furthermore, to investigate whether the needles with the largest discrepancy between application and loading are essential to treatment planning. Materials and methods For 22 patients we analysed the applied and loaded needle patterns, and examined the dosimetric results for small (<30 cm 3 ) and large (≥30 cm 3 ) CTV HR . We removed from the clinical plans (CP) the needles applied most, but with the lowest loading frequency and intensity and re-optimized these plans (RP). Results On average 5.8 needles were applied and 4.8 loaded per fraction, with average intensity 22% (17% for small, 29% for large CTV HR ). Mid-lateral needles were applied and loaded most frequently and intensely. The average CTV HR D 90% prescribed dose was 88.8 Gy (SD 4.2) EQD2 10 , the average OAR D 2 cm 3 limit was respected. Omitting the mid-ventral needles, minimal statistically significant differences were found in dose distributions between RP and CP. Conclusions Applying on average 5.8 needles per fraction it was possible to meet the planning criteria for targets and OARs in three BT fractions for both small and large CTV HR . The mid-ventral needles were not essential in treatment planning, unless situated in the vicinity of the GTV res . [ABSTRACT FROM AUTHOR]

The current study aimed to determine the optimum diagnostic imaging technique out of magnetic resonance imaging (MRI), 18F‑fludeoxyglucose positron emission tomography/computed tomography ([18F] FDG‑PET/CT, otherwise known as PET/CT) and [18F] FDG‑PET/MRI (otherwise known as PET/MRI) for the pelvic lymph node staging (N‑staging) of untreated cervical carcinoma (CC). A total of 27 patients were included in the present study. All patients had undergone pre‑treatment with PET/CT and MRI ≤45 days prior to undergoing a lymphadenectomy. The results from PET (separated from PET/CT), MRI and the statistically combined results of (virtual) PET/MRI were compared to those from histological analyses (the gold standard). A per‑patient‑based analysis of the detection of pelvic lymph node metastases indicated that PET/MRI had a sensitivity of 64%. The specificity of PET/CT and MRI were 69 and 62%, respectively. The positive predictive value (PPV) was 69 and 64% for PET/CT and MRI, respectively. The negative predictive value (NPV) was 64 and 62% for PET/CT and MRI, respectively. The sensitivity of the PET‑guided PET/MRI and the MRI‑guided PET/MRI was 64% for both. The specificity of the PET‑guided PET/MRI and the MRI‑guided PET/MRI was 77 and 62%, respectively. The PPV was 75% for PET‑guided PET/MRI and 64% for MRI‑guided PET/MRI, and the NPV was 67 and 62%, respectively. PET/CT and the virtual PET/MRI exhibited the same low sensitivity (64%). PET/MRI exhibited slightly better results than PET/CT regarding specificity (77 vs. 69%, respectively), PPV (75 vs. 69%, respectively) and NPV (67 vs. 64%, respectively). The results of the present study suggested that PET/CT and MRI are not optimal diagnostic modalities, and that PET/MRI does not necessarily lead to better results than PET/CT, in the pelvic N‑staging of CC. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the third most common cancer among women. The evidence from Russia, however, is scarce. We studied the incidence of and mortality from cervical cancer in northwest Russia, and assessed determinants of survival among cervical cancer patients. Methods: This registry-based historical cohort study obtained data on all primary cases of cervical cancer in the Arkhangelsk region in 2000-2014 from the Arkhangelsk Regional Cancer Registry. One- and 5-y survival was calculated using life tables. Factors associated with survival were studied using Kaplan-Meier curves and Cox regression. Results: The incidence increased from 10.9 per 100 000 in 2000 to 20.9 per 100 000 in 2014, while mortality increased from 2.0 to 7.8 per 100 000 during the same period. One- and 5-y survival was 77.4% (95% CI 75.4 to 79.4) and 60.0% (95% CI 54.6 to 61.5), respectively. Significant inverse association was observed between survival and stage of cancer. Patients with adenocarcinoma (HR=1.6, 95% CI 1.2 to 2.2), other histological types of cancer (HR=1.8, 95% CI 1.4 to 2.4) and those with undefined histologic type (HR=3.8, 95% CI 2.5 to 5.8) had shorter survival than patients with squamous cell carcinoma. Conclusions: Incidence of and mortality from cervical cancer in northwest Russia is considerably higher than in developed countries. Increased incidence in recent years may be attributed to increased screening. [ABSTRACT FROM AUTHOR]

Objective: To compare the differences in the dose‐volume histograms between knowledge‐based intensity‐modulated radiotherapy (K‐IMRT) plans and conventional IMRT (C‐IMRT) plans of 20 patients with cervical cancer. Methods: A total of 70 cervical cancer patients were selected in the present study. Of these, 60 patients were selected randomly as a model group. The remaining 10 patients with overlap volume of target and organs at risk were categorized as group E1 for open‐loop verification. A total of 10 patients from the model group were selected randomly as group E2 for closed‐loop verification. Results: The dose parameters of the target in the K‐IMRT and C‐IMRT plans showed no significant difference. The maximum dose and homogeneity index of group E2 showed no significant difference (P > 0.05) in their K‐IMRT and C‐IMRT plans. The dose parameters in the K‐IMRT plans of organs at risk were superior to those in the C‐IMRT plans. For group E1, V20 of the rectum, and V15, V20, and V25 of the left and right femoral heads in the K‐IMRT plans decreased as compared with those in the C‐IMRT plans (P < 0.05). For group E2, V25, V30, V35, and D50 of the bladder; V25 and V30 of the rectum; and V15, V20, and V25 of the left and right femoral heads in the K‐IMRT plans decreased as compared with those in the C‐IMRT plans (P < 0.05). Conclusion: It is feasible to optimize the IMRT plans for cervical cancer patients with the overlap volume of the target and organs at risk using knowledge‐based radiation treatment automatically. [ABSTRACT FROM AUTHOR]

Background: One international and three local organizations developed the Santa Ana Women's Health Partnership (SAWHP) to address cervical cancer in Santa Ana Huista, Huehuetenango, Guatemala. This paper describes the structure, outcomes, and lessons learned from our community partnership and program. Methods: The community partnership developed a singlevisit approach (SVA) program that guided medically underserved women through screening and treatment of cervical cancer. Lessons Learned: The program promoted acceptability of SVA among rural women by engaging local female leaders and improving access to screening services. The program's approach focused on maximizing access and generated interest beyond the coverage area. Distrust among the community partners and weak financial management contributed to the program's cessation after 4 years. Conclusions: The SAWHP design may guide future implementation of cervical cancer screening programs to reach medically underserved women. Open, ongoing dialogue among leaders in each partner institution is paramount to success. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) detection based on cervical cytology specimens is useful for cervical cancer screening. The aim of this study was to compare Mojin HPV kit (a newly developed HPV genotyping assay) with the Cobas 4800 HPV test in detecting high-risk (HR) HPV. Methods: A total of 347 cervical exfoliated cell specimens were tested using the Mojin HPV kit and Cobas 4800 HPV test. When the results from the two tests were inconsistent, gene sequencing was performed for correction. Results: For HR-HPV, the results of the two assays agreed by 96.3% [Kappa = 0.911; 95% confidence interval (CI): 0.863 - 0.958)]. The positive and negative coincidence rates between the two tests were 96.0% (95% CI: 92.7% - 98.0%) and 97.0% (95% CI: 91.5% - 99.4%), respectively. Of the 13 samples with discordant results, 3 samples were false positive and 10 samples were true negative for Mojin HPV test, according to the identification by sequencing. For HPV16 genotyping, the total coincidence rate between the 2 tests was 100% (Kappa = 1.000), and 99.7% (Kappa = 0.973; 95% CI: 0.905 - 1.000) for HPV18. Conclusions: Mojin HPV kit may be as effective as Cobas 4800 HPV assay in detecting the total HR-HPV, especially HPV16 or HPV18. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the dosimetric parameters, clinical complications, and efficacy of volumetric modulated arc therapy (VMAT) and fixed-field intensity-modulated radiotherapy (f-IMRT) in radical radiotherapy for cervical cancer without lymphadenectasis. Methods: 84 cervical cancer patients undergoing treatment with VMAT and f-IMRT were selected. Dose-volume histograms were used to evaluate the dose distribution in the planning target volume (PTV) and organs at risk. The clinical complications and efficacy were observed. Results: The homogeneity index (HI) and the conformity index (CI) of VMAT plans were both superior to the HI and CI of f-IMRT plans (p = 0.043, 0.025). VMAT plans resulted in a reduction in the V30 of the rectum and V40 of the bladder (p = 0.002). Furthermore, the monitor units (MUs) for VMAT were less than a quarter of those for f-IMRT. The treatment time for VMAT was less than a half of that for f-IMRT. Both clinical complications and efficacy showed no significant differences. Conclusion: VMAT plans showed superior dose coverage of the PTV, better protection of the rectum and bladder in dosimetry, and significantly reduced MUs and treatment time compared with f-IMRT. Clinical results were similar for both plans. [ABSTRACT FROM AUTHOR]

Objectives: Implicit associations influence behaviour, but their impact on cancer screening intentions is unknown.Methods: We assessed implicit associations with cervical cancer screening using an evaluative priming task. Participants were shown primes ('Pap test', neutral or non-word) followed by positive or negative target words. The test is based on the assumption that response times are shorter if primes and targets are strongly associated in the participant's mind. The Dutch screening program targets women aged 30-60, 226 of them completed online assessments twice. Prior to the second assessment participants were randomized to reading versus not reading the leaflet about the cervical screening program.Results: After controlling for knowledge and screen history, response times for 'Pap test' no longer differed between positive and negative targets. Implicit associations were not correlated with explicit attitudes or screening intentions. Reading the screening leaflet resulted in improved knowledge levels (p<0.001), but implicit associations, explicit attitudes, and screening intentions remained similar.Conclusion: Cervical cancer screening intentions were related to explicit attitudes, but not to implicit associations. The screening leaflet did not affect screening intentions.Practice Implications: We recommend achieving a deepened interest in the screening program among risk groups, e.g. by adapting the information leaflet. [ABSTRACT FROM AUTHOR]

Background & objectives: Invasive cervical cancer patients are primarily treated with chemoradiation therapy. The overall and disease-free survival in these patients is variable and depends on the tumoral response apart from the tumour stage. This study was undertaken to assess whether in vivo changes in gene promoter methylation and transcript expression in invasive cervical cancer were induced by chemoradiation. Hence, paired pre- and post-treatment biopsy samples were evaluated for in vivo changes in promoter methylation and transcript expression of 10 genes (ESR1, BRCA1, RASSF1A, MYOD1, MLH1, hTERT, MGMT, DAPK1, BAX and BCL2L1) in response to chemoradiation therapy. Methods: In patients with locally advanced invasive cervical cancer, paired pre- and post-treatment biopsies after 10 Gy chemoradiation were obtained. DNA/RNA was extracted and gene promoter methylation status was evaluated by custom-synthesized methylation PCR arrays, and the corresponding gene transcript expression was determined by absolute quantification method using quantitative reverse transcription PCR. Results: Changes in the gene promoter methylation as well as gene expression following chemoradiation therapy were observed. BAX promoter methylation showed a significant increase (P< 0.01) following treatment. There was a significant increase in the gene transcript expression of BRCA1 (P< 0.01), DAPK1 and ESR1 (P< 0.05), whereas MYOD1 and MLH1 gene transcript expression was significantly decreased (P< 0.05) following treatment. Interpretation & conclusions: The findings of our study show that chemoradiation therapy can induce epigenetic alterations as well as affect gene expression in tissues of invasive cervical cancer which may have implications in determining radiation response. [ABSTRACT FROM AUTHOR]

Abstract: Cervical cancer is the fourth most common cancer affecting women worldwide. Among many factors, the presence of cancer stem cells, a subpopulation of cells inside the tumor, has been associated with a worse prognosis. Considering the importance of gene expression studies to understand the biology of cervical cancer stem cells (CCSC), this work identifies stable reference genes for cervical cancer cell lines SiHa, HeLa, and ME180 as well as their respective cancer stem‐like cells. A literature review was performed to identify validated reference genes currently used to normalize RT‐qPCR data in cervical cancer cell lines. Then, cell lines were cultured in regular monolayer or in a condition that favors tumor sphere formation. RT‐qPCR was performed using five reference genes: ACTB, B2M, GAPDH, HPRT1, and TBP. Stability was assessed to validate the selected genes as suitable reference genes. The evaluation validated B2M, GAPDH, HPRT1, and TBP in these experimental conditions. Among them, GAPDH and TBP presented the lowest variability according to the analysis by Normfinder, Bestkeeper, and ΔCq methods, being therefore the most adequate genes to normalize the combination of all samples. These results suggest that B2M, GAPDH, HPRT1, and TBP are suitable reference genes to normalize RT‐qPCR data of established cervical cancer cell lines SiHa, HeLa, and ME180 as well as their derived cancer stem‐like cells. Indeed, GAPDH and TBP seem to be the most convenient choices for studying gene expression in these cells in monolayers or spheres. [ABSTRACT FROM AUTHOR]

Purpose: Plasma paclitaxel (PTX) concentration 24 h or later after PTX administration may predict myelosuppression. Here, we explored predictive markers for neutropenia induced by intravenous administration of PTX in an outpatient clinic.Methods: Thirty women suffering from uterine, ovarian or cervical cancer were enrolled in this study. PTX (mean dose: 167 mg/m2) was intravenously infused and followed by carboplatin. Plasma samples were obtained 4 h after PTX administration. Genotyping was carried out for CYP3A5*3, ABCB1 1236 C>T, 2677 G>T/A, and 3435 C>T.Results: There was no significant relationship between genotype and reduced neutrophil count. Neutrophil reduction rate correlated with the patient's height, neutrophil count on the day of administration, and plasma PTX concentration. Multiple regression analysis with those three indices explained 47.7% of the interindividual variability of the neutrophil reduction rate. The model with plasma PTX concentration, patient's height, and plasma 6-α-hydroxy-paclitaxel /PTX concentration ratio also explained 30.0% of the interindividual variability for the neutrophil nadir count after PTX administration.Conclusions: These results indicate that neutrophil reduction after PTX administration can be partially predicted by multiple regression analysis involving plasma concentration data collected at outpatient clinics. [ABSTRACT FROM AUTHOR]

Objective: This study aims to analyze the published literatures on the effect of less radical fertility-preserving procedures, such as conization or simple trachelectomy, on oncological outcomes in IA1 cervical cancer patients with lymphovascular space invasion (LVSI) through a systematic-review. Methods: The EMBASE and MEDLINE databases and Cochrane Library were searched for published studies reporting the oncological outcomes of conization/simple trachelectomy in these patients, through April 2017. The endpoints were recurrence and mortality rates. Data were presented as per the Meta-analysis Of Observational Studies in Epidemiology checklist. Practice guidelines were generated via the Grading of Recommendation, Assessment, Development and Evaluation system. Results: From 6,755 records, 94 full-texts articles were reviewed for eligibility, and five studies were included in this systematic review. All included studies were nonrandomized studies: two case-control studies comparing conization (n = 14) with hysterectomy (n = 24), and the other three were interrupted time series including conization (n = 20) and simple vaginal trachelectomy (n = 59). During the median follow-up duration of 43 months, no recurrence was reported in both conization and simple trachelectomy groups in IA1 patients with LVSI. From three studies reporting the fertility outcomes, the rates of pregnancy, live birth, preterm delivery, and second-trimester miscarriage were 73% (35/48), 64% (32/50), 10% (5/48), and 6% (3/48), respectively. Conclusion: Results suggest that simple trachelectomy or conization could be performed for IA1 cervical cancer patients with LVSI who want to preserve fertility, although these results are only based on a small number of nonrandomized studies (recommendation grade 2 = weak; evidence level D = very low). Further randomized trials with long-term study period are needed to address this issue. [ABSTRACT FROM AUTHOR]

Background: The objective of this study is to analyze the treatment outcome and secondary reactions in 98 patients with stage I-III cervical carcinoma who underwent postoperative radiotherapy. Methods: From 2006 to 2014, 98 patients with stage I-III cervical carcinoma were treated with postoperative radiotherapy. The major histological type, found in 92.86% of the patients (91 cases), was squamous cell carcinoma. Patients were staged according to the 2002 TNM guidelines. The postoperative radiotherapy methods included two-field irradiation (16 patients, 16.32%), four-field box irradiation (16 patients, 16.32%), and intensity-modulated radiotherapy (IMRT; 66 patients, 67.36%). The survival rates were represented using Kaplan-Meier curves, and prognosis analyses were performed using Cox multivariate analyses. Results: The 5-year overall survival and progression-free survival rates were 82.0 and 76.0%, respectively. Only one patient (1.02%) developed a grade 3 acute radiation enteritis, while grade 3 and 4 myelosuppression was noted in 17 patients (17.35%) and one patient (1.02%), respectively. Multivariate analyses showed that anemia before radiotherapy and tumor size were predictors of the OS (P = 0.008, P = 0.045) rates. Conclusions: Postoperative radiotherapy for patients with risk factors of cervical cancer procured good efficacy levels with mild side effects. Anemia and tumor size were important OS predictors. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of leukemia inhibitory factor receptor ( LIFR) and Hippo-YAP signaling pathway in the lung metastasis of cervical cancer. Methods ① The real-time fluorescence quantitative polymerase chain reaction ( qRT-PCR) was used to detect the expression of LIFRmRNAin the primary cancerous tissues，adjacent non-cancerous tissues and metastasis tissues from 50 cases of patients with cervical cancer and lung metastasis.② Recombinant lentiviral plasmid containing LIFRor its negative control ( vector) were used to infect the human cervical cancer cell line SiHa. After screening with 2. 0 #g/mL puromycin， the cells that stably expressed LIFR ( observation group) or vector (control group) were obtained. Western blotting was used to detect the expression of LIFRand Hippo-YAP signaling pathway related proteins YAP，P-YAP，TAZ，and p-TAZ. The cells of the two groups were injected into the BALB/c nude mice through the tail vein. After 4 weeks，the nude mice were killed and the lung tissue was removed for HE staining. The number of all the metastases in the lung tissues was counted microscopically. Results ① The relative expression of LIFR mRNA in the primary tumor was higher than that in the adjacent non-cancerous tissues，and the relative expression of LIFR mRNAin the metastasis tissues was lower than that in primary tumor and adjacent non-cancerous tissues ( all !< 0. 05 ). ② The relative expression of LIFR，p-YAP and p-TAZ proteins in the SiHa cells which overexpressed LIFRwas higher than that in the control cells ( all !< 0. 05 ) . There was no significant difference in YAP and TAZ protein expression between the control group and observation group ( all !> 0. 05 ). The lung metastases in the SiHa cells with overexpressed LIFR and control cells were 9 ± 2 and 60 ± 5，respectively ( all !< 0. 05 ) . Conclusion Overexpression of LIFR can promote the phosphorylation of Hippo-YAPsignaling pathway proteins YAPand TAZ $ and then inhibit tlie formation of lung metastasis of cervical cancer cells. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to investigate the optimal gene and functional-related gene set in cervical cancer through combing the differential expression (DE) and differential coexpression (DC) analysis.Materials and Methods: To achieve this, we first measured expression data of cervical cancer by incorporating DE and DC effects utilizing absolute t-value in t-statistic and Z-test, respectively. Then, we selected the optimal threshold pair to determine both high DE and high DC (HDE_HDC) partition on the basis of Chi-square maximization, and the best threshold pair divided all genes into four parts, including HDE_HDC, high DE and low DC (HDE_LDC), low DE and high DC (LDE_HDC), and low DE and low DC (LDE_LDC). Using the known functional gene sets, functional relevance of partition genes was explored to determine the best-associated gene set based on the functional information (FI) conception.Results: Under the optimal threshold pair of 3.629 and 1.108 for DE and DC, respectively genes were divided into four partitions: HDE_HDC (311 genes), HDE_LDC (2072 genes), LDE_HDC (seventy genes), and LDE_LDC (1623 genes). Meanwhile, the gene set epidermis development was the best-associated gene set with the largest △G* = 10.496. Among the genes of epidermis development, zinc finger protein 135 (ZNF135) attained highest minimum FI gain of 41.226.Conclusion: The combination of DE and DC analysis showed higher mean FI relative to individual DE and DC analyses. We successfully exhibited the optimal gene set epidermis development and gene ZNF135, which might be crucial for the prevention and treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose In 2005, the Cervical Cancer Prevention Program in Zambia (CCPPZ) was implemented and has since provided cervical cancer screen-and-treat services to more than 500,000 women. By leveraging the successes and experiences of the CCPPZ, we intended to build capacity for the early detection and surgical treatment of breast cancer. Methods Our initiative sought to build capacity for breast cancer care through the (1) formation of a breast cancer advocacy alliance to raise awareness, (2) creation of resource-appropriate breast cancer care training curricula for mid- and high-level providers, and (3) implementation of early detection and treatment capacity within two major health care facilities. Results Six months after the completion of the initiative, the following outcomes were documented: Breast health education and clinical breast examination (CBE) services were successfully integrated into the service platforms of four CCPPZ clinics. Two new breast diagnostic centers were opened, which provided access to breast ultrasound, ultrasound-guided core needle biopsy, and needle aspiration. Breast health education and CBE were provided to 1,955 clients, 167 of whom were evaluated at the two diagnostic centers; 55 of those evaluated underwent core-needle biopsy, of which 17 were diagnosed with invasive cancer. Newly trained surgeons performed six sentinel lymph node mappings, eight sentinel lymph node dissections, and 10 breast conservation surgeries (lumpectomies). Conclusion This initiative successfully established clinical services in Zambia that are critical for the early detection and surgical management of breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To compare outcomes of patients with pure adenocarcinoma-in-situ (AIS) and mixed AIS/CIN 2/3 lesions including the incidence of AIS persistence, recurrence and progression to adenocarcinoma.Design: Retrospective cohort study.Setting: Statewide population in Western Australia.Population: Women diagnosed with AIS between 2001 and 2012.Methods: We conducted a retrospective, population-based cohort study.Main Outcome Measures: De-identified linked data were utilised to ascertain the association between patient age at excisional treatment, margin status, lesion type, lesion size, and risk of persistent AIS (defined as the presence of AIS <12 months from treatment), recurrent AIS (≥12 months post-treatment), and adenocarcinoma.Results: 636 patients were eligible for analysis. The mean age was 32.3 years and median follow-up interval was 2.5 years. Within the study cohort, 266 patients (41.8%) had pure AIS and 370 (58.2%) had mixed AIS/CIN 2/3. Overall, 47 patients (7.4%) had AIS persistence/recurrence and 12 (1.9%) had adenocarcinoma. Factors associated with persistence/recurrence were pure AIS (hazard ratio (HR) 2.3; 95%CI 1.28-3.94; P = 0.005), age >30 years (HR 2.1; 95%CI 1.16-3.81; P = 0.015), positive endocervical margins (HR 5.8; 95%CI 3.05-10.92; P = <0.001) and AIS lesions >8 mm (HR 2.5; 95%CI 1.00-6.20; P = 0.049). A histologically positive AIS ectocervical margin was not associated with persistence/recurrence.Conclusion: In this study, pure AIS was associated with greater risk of persistence/recurrence than was mixed AIS/CIN 2/3. AIS lesions >8 mm and positive endocervical margins were significant predictors for persistent or recurrent disease.Tweetable Abstract: Pure cervical adenocarcinoma-in-situ (AIS) may have greater risk of recurrence than AIS co-existing with CIN 2/3. [ABSTRACT FROM AUTHOR]

Background and objective: Cervical cancer is one of the most common malignancies among women. The present study aims to assess the sign and symptoms of cervical cancer in women aged between 25-80 years. Materials and Method: The current study was a case control study. Total age matched 75 cases and controls were taken. The sampling technique for cases was total enumeration technique and for controls purposive sampling was used. Women who satisfied the inclusion criteria were included in study. A questionnaire was developed to identify the sign and symptoms of cervical cancer amongst the subjects. Face to face interview was conducted with the subjects. Result: There was significant difference (p<0.05) of pain during sexual intercourse, bleeding during sexual intercourse, lower back pain, itching and burning in genital area, vaginal discharge that smell unpleasant, bleeding between period, and excessive vaginal bleeding with development of cervical cancer. In logistic regression excessive bleeding and lower back pain showed a significant association with development of carcinoma of cervix. Conclusion: Pain and bleeding during sexual intercourse, lower back pain, itching and burning in genital area, vaginal discharge that smell unpleasant, bleeding between period, and excessive vaginal bleeding were the sign and symptom of cervical cancer. With prior identification of sign and symptoms of cervical cancer can identify carcinoma of cervix in early stages and prompt treatment can be started. [ABSTRACT FROM AUTHOR]

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive and often fatal pulmonary disease induced by tumor emboli within the small pulmonary arteries. PTTM presents clinically as progressive hypoxia and pulmonary hypertension. Most cases of PTTM are caused by an adenocarcinoma of the stomach. We present the first case report of PTTM caused by cervical squamous cell carcinoma. An 82-year-old woman presented with vaginal bleeding and exertional dyspnea. A cervical mass biopsy showed squamous cell carcinoma. Computed tomography revealed ground glass opacity of the bilateral peripheral lung fields. Hypoxia and pulmonary hypertension gradually worsened after admission. Treatment for acute heart failure was started, but was ineffective. She died of respiratory failure 31 days after admission. She was diagnosed at autopsy as having PTTM induced by cervical squamous cell carcinoma. PTTM needs to be considered in any patient with advanced cancer and lung-related issues to rule out metastatic disease, even in the absence of imaging findings. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to do the following: (1) describe progression free survival (PFS) and overall survival (OS) of women with cervical cancer presenting with occult supraclavicular lymph node (SCLN) metastases, identified by positron emission tomography CT (PET-CT) and (2) compare OS of patients with isolated SCLN metastases to that of patients with SCLN and extranodal metastatic disease.Methods: Patients were identified retrospectively. Treatment intent was abstracted. PFS and OS in the high-dose chemo-radiotherapy (RT), palliative RT, and supportive treatment groups, as well as OS of patients with SCLN metastases only vs. SCLN and extranodal metastases were calculated.Results: Fourteen patients received high-dose chemo-RT, 32 received palliative RT, and 6 received supportive care (n = 52). Median PFS was 3 months in high-dose chemo-RT group and 1 month in palliative RT (p = ns). Median OS was 12 months in high-dose chemo-RT group, 7 months in palliative RT group, and 2 months in palliative care group (p = 0.05). OS was significantly different between patients with isolated SCLN disease vs. SCLN and extranodal disease, that is, 10.5 vs. 3 months (p = 0.009, χ2 = 6.9).Conclusions: In this limited analysis, median OS of cervical cancer patients with PET/CT-positive SCLN metastases was the longest when treated with high-dose chemo-RT. Patients with SCLN and extranodal metastases experienced significantly shorter OS, as compared to patients with SCLN only disease. [ABSTRACT FROM AUTHOR]

Aims and objective: The common psychological and emotional responses to cancer arise from knowledge of life threatening diagnosis, its prognostic uncertainty, and fear about death and dying. Carcinoma cervix (cervical cancer) is one of the major life threatening conditions in females and carries a risk of high mortality. This study was carried out with the aim to find out psychiatric morbidities in patients of carcinoma cervix so that a proper evaluation of their mental health and comprehensive management, and improving their quality of life can be planned. Methodology: One hundred female patients of age range between 31-65 years, recently diagnosed as carcinoma cervix were screened for psychiatric morbidity on a structured proforma containing socio-demographic details. The diagnosis and staging of carcinoma cervix was based on revised FIGO (International Federation of Gynecology and Obstetrics) and psychiatric diagnosis was made as per DSM-IV-TR. Hamilton Anxiety Rating Scale (HARS), Hamilton Rating Scale for Depression (HAM-D), Brief Psychiatric Rating Scale (BPRS), and Yale-Brown Obsessive Compulsive (Y-BOCS) were used to assess the severity of the psychiatric illness. Result: Majority of the patients belonged to age group 51-60 years. Most of them were Hindu, housewives, and belonged to lower socioeconomic status. Psychiatric morbidity was detected in 55% patients; majority of them having duration of cancer for less than six months. Twenty six per cent patients suffered from major depressive disorder, 17% had anxiety disorder, and eight per cent were detected as adjustment disorder with depressed mood while four per cent patients had only insomnia. Patients presenting in late stage of cancer had more severe psychiatric disturbances as compared to patients in early stage of cancer. Conclusion: Significant comorbid psychiatric illness was detected in patients of carcinoma cervix. The proper evaluation, identification, and management of associated psychiatric illness will improve the mental health and quality of life of patients suffering from carcinoma cervix. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is well known as a major etiological risk factor associated with carcinogenesis in uterine cervical cancer. However, few reports have investigated the association between HPV genotype and outcome in patients with uterine cervical cancer following radiotherapy (RT). The aim of the present study was to investigate the association between the HPV genotype and clinical outcome following RT in Japanese patients with uterine cervical cancer. Between November 2001 and August 2006, 157 Japanese women with uterine cervical cancer were treated with RT or concurrent chemoradiotherapy with curative intent. Pretreatment, formalin-fixed, paraffin-embedded biopsies were obtained from 83 patients. HPV genotypes were determined using the polymerase chain reaction method. Patients were categorized, according to HPV L1 protein sequence homology, into the HPV α-9 (HPV 16, 31, 33, 52, and 58), HPV α-7 (HPV 18, 39, 45, 59, and 68) or 'other' (HPV 51 and 56) groups. Associations between HPV genotype and clinical outcome following RT were evaluated. A total of 54 (65.1%) tumors were HPV α-9-positive, 13 (15.7%) were HPV α-7-positive, 2 (2.4%) were categorized under 'other' and 14 (16.9%) were HPV-negative. There were no significant differences in age, FIGO stage, regional lymph node metastases rate at diagnosis, or concurrent chemotherapy administration between the HPV α-9 and α-7 groups. The median follow-up period was 52 months (range, 2-156 months). The 5-year disease-free survival rates were 54.5 and 30.8% in the HPV α-9 and α-7 groups, respectively (P=0.034), and the 5-year distant metastasis rates were 38.0 and 69.2%, respectively (P=0.015). There were no significant differences in the 5-year local control or overall survival (OS) rates between the two groups. HPV genotype affected the 5-year distant metastatic rate, however not the 5-year local control or OS rate in patients with uterine cervical cancer following RT. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prediction of response to concurrent chemoradiotherapy (CCRT) through a combination of pretreatment multi-parametric magnetic resonance imaging (MRI) with clinical prognostic factors (CPF) in cervical cancer patients.Methods: Sixty-five patients underwent conventional MRI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced MRI (DCE-MRI) before CCRT. The patients were divided into non- and residual tumour groups according to post-treatment MRI. Pretreatment MRI parameters and CPF between the two groups were compared and prognostic factors, optimal thresholds, and predictive performance for post-treatment residual tumour occurrence were estimated.Results: The residual group showed a lower maximum slope of increase (MSIL) and signal enhancement ratio (SERL) in low-perfusion subregions, a higher apparent diffusion coefficient (ADC) value, and a higher stage than the non-residual tumour group (p < 0.001, p = 0.003, p < 0.001, and p < 0.001, respectively). MSIL and ADC were independent prognostic factors. The combination of both measures improved the diagnostic performance compared with individual MRI parameters. A further combination of these two factors with CPF exhibited the highest predictive performance.Conclusions: Pretreatment MSIL and ADC were independent prognostic factors for cervical cancer. The predictive capacity of multi-parametric MRI was superior to individual MRI parameters. The combination of multi-parametric MRI with CPF further improved the predictive performance.Key Points: • Pretreatment MSI L and ADC were independent prognostic factors for post-treatment residual tumours. • The residual groups showed lower MSI L , higher ADC and higher stage. • The predictive capacity of multi-parametric MRI was superior to individual MRI parameters. • The combination of multi-parametric MRI with CPF exhibited the highest predictive performance. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the commonest gynecological malignancy in our environment and is an Acquired Immuno-Deficiency Syndrome (AIDS)-associated malignancy. Documented data on the Human Immune-deficiency Virus (HIV) seroprevalence among patients with cervical cancer in our environment are scarce. Objective: The aim of this study is to determine the prevalence of HIV infection in women with cancer of the cervix. Study Design: The work is a descriptive survey by design, concentrating in frequency of occurrences of prevalence of the disease in either cases for a number of years retrospectively carried out at the Radiotherapy and Oncology Centre of Ahmadu Bello University Teaching Hospital (ABUTH) Zaria. Setting: The study was carried out at the Radiotherapy and Oncology Centre of ABUTH, Zaria. Materials and Methods: A 5 years retrospective review of patients with histologically-proven cancer of the cervix seen in the Radiotherapy and Oncology Centre, ABUTH, Zaria, North-Western Nigeria was undertaken. Data such as age, clinical stage of disease and HIV seropositivity at presentation were retrieved from the case files. Data analysis was done using the SPSS statistical package version IBM 23 and results presented in frequencies and percentages and charts for graphical presentation. Results: A total of 1,639 patients seen over a period of 5 years were reviewed. The age range of both groups of patients was from 28 years to 92 years with a mean age of 50.5 years. One thousand five hundred and seventy-three of the patients (96%) were seronegative to the HIV tests while 66 (4%) were seropositive. The age range of the seropositive patients was 28 - 49 years with a mean age of 38.1 years. Their peak age at presentation was 30 - 39 years. Similarly, the age range of the seronegative patients was 30 – 92 years with a peak at 40-49 years. 51 (89.5%) of the HIV seropositive patients presented with advanced clinical stage disease, i.e, International Federation of Obstetrics and Gynecology (FIGO) stage 2B and above. 1,363 (93%) of the HIV seronegative patients presented with FIGO 2B disease and above, both scenario illustrating the general trend of late presentation of cancer patients to hospital in our environment. Conclusion: The study shows that the prevalence of HIV infection among cervical cancer patients is low in Zaria, with earlier age of development of cervical cancer among HIV seropositive patients compared to HIV seronegative counterparts. Both group of patients present with cervical cancer at an advanced stage. More studies therefore needed to be done to identify the predisposing factors to the high incidence of invasive cervical cancer in our environment and introduction of cervical cancer screening at an earlier age among HIV seropositive patients. [ABSTRACT FROM AUTHOR]

The primary objective was to determine the theoretical number of colposcopies at a resident clinic if the 2012 American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines were applied. The secondary objective was to determine the actual number of colposcopies before and after the ASCCP guidelines. This was a two-part descriptive study. The first part applied the 2012 ASCCP guidelines to all pre-guideline colposcopy cases at a single resident clinic. These theoretical results were then compared to the actual number of colposcopies. The second part compared the actual number of colposcopies during the one-year time period before and after the guidelines. Chi-Square tests and Fisher's Exact tests were used to examine the association of categorical variables. Seventy-three colposcopies were performed during the pre-guideline period. After applying the 2012 ASCCP guidelines, 52.1% would not have been indicated, resulting in 35 colposcopies. The largest reductions would have occurred in patients with low grade cytologic abnormalities. Applying the new guidelines, patients 24 years and younger would have been less likely than patients ages 25 to 64 to require colposcopy (P<.001). Fifty-eight indicated colposcopies were actually performed during the post-guideline period. While there was a decrease in the number of colposcopies performed post-guidelines, the decrease was not as dramatic as expected. From a training standpoint, as indications for colposcopy decrease, fewer training opportunities are available for residents. In particular, residents will have less experience evaluating low grade cytologic abnormalities in younger women. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the commonest female cancers in Sudan due to the absence of HR-HPV screening and vaccination programs. The aim of this study was to screen for the existence of cervical cancer related herpes viruses (HPV, EBV, CMV and EBV) among Sudanese women with cervical cancer. This was analytical case control study conducted in Khartoum state-Sudan during period from October 2013 to June 2016. One hundred and eighty paraffin-embedded tissue blocks were included in this study. Of the 180 tiaaue's blocks, 98 blocks were from patients with cervical squamous cell carcinoma (case group) and 82 were from cervical tissue's blocks malignancy-free (control group). Screening for herpes viruses (HPV, EBV, CMV and EBV) were performed using Immunohistochemistry (IHC) techniques. HR-HPV infection was detected in 28.6% of the cases, and 2.4% of the controls. Association between HR-HPV and cervical carcinoma was found to be statistically significant P < 0.0001. CMV infection was detected in 15.3% of the cases and 1.2% of the controls with statistically significant difference, the P < 0.0001. HSV-2 revealed positivity in 6.1% of the cases and in 1.2% of the controls with no statistically significant correlation. EBV was positive in 2% of the cases, while none of the control was found positive. HR-HPV and EBV are prevalent etiological factors that contribute to the etiology of cervical carcinoma in Sudan. HSV-2 and EBV were insignificantly found in cervical cancerous leions. [ABSTRACT FROM AUTHOR]

Objective: To assess the knowledge, attitude and practice pattern regarding cervical cancer, its screening and prevention among registered nurses from tertiary care hospitals. Methods: A descriptive cross sectional study was conducted with convenient sampling technique to assess the knowledge, attitude and practice regarding cervical cancer its screening and prevention among registered nurses from 15th January to 15th July 2016. Over all 129 nurses who had already completed their nursing training and willing to participate in the study were enrolled. A self structured pretested questionnaire was used to assess their existing knowledge, attitude and practices regarding prevention and screening of cervical cancer. For each correct answer score 1 marks was given. The findings of the study were developed in frequencies and percentages of each variable. Results: The overall mean scores of the knowledge regarding cervical cancer, its screening and prevention among registered nurses was 5.19 ± 3.69 out of 14 score. The attitude of the nurses regarding cervical cancer, its screening and prevention was poor as mean attitude was 2.88±1.44 out of 8 score. Similarly practicing pattern was also assessed which was found very poor as mean was just 1.35 ±0.95 out of 4 score. Conclusion: Overall knowledge of the nurses regarding cervical cancer, its screening and prevention did not found up to the required standard. The attitude and practice pattern was found much lesser as compare to knowledge, which shows that continous education is required to upgrade these for prevention of the cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the fourth most common malignancy in women worldwide. However, screening with human papillomavirus (HPV) molecular tests holds promise for reducing cervical cancer incidence and mortality in low- and middle-income countries. The performance of the Abbott RealTime High-Risk HPV test (AbRT) was evaluated in 83 cervical smear specimens and compared with a conventional nested PCR coupled to high-throughput sequencing (HTS) to identify the amplicons. Results: The AbRT assay detected at least one HPV genotype in 44.57% of women regardless of the grade of cervical abnormalities. Except for one case, good concordance was observed for the genotypes detected with the AbRT assay in the high-risk HPV category determined with HTS of the amplicon generated by conventional nested PCR. Conclusions: The AbRT test is an easy and reliable molecular tool and was as sensitive as conventional nested PCR in cervical smear specimens for detection HPVs associated with high-grade lesions. Moreover, sequencing amplicons using an HTS approach effectively identified the genotype of the hrHPV identified with the AbRT test. [ABSTRACT FROM AUTHOR]

Background: Computational intelligence methods, including non-linear classification algorithms, can be used in medical research and practice as a decision making tool. This study aimed to evaluate the usefulness of artificial intelligence models for 5-year overall survival prediction in patients with cervical cancer treated by radical hysterectomy.Methods: The data set was collected from 102 patients with cervical cancer FIGO stage IA2-IIB, that underwent primary surgical treatment. Twenty-three demographic, tumor-related parameters and selected perioperative data of each patient were collected. The simulations involved six computational intelligence methods: the probabilistic neural network (PNN), multilayer perceptron network, gene expression programming classifier, support vector machines algorithm, radial basis function neural network and k-Means algorithm. The prediction ability of the models was determined based on the accuracy, sensitivity, specificity, as well as the area under the receiver operating characteristic curve. The results of the computational intelligence methods were compared with the results of linear regression analysis as a reference model.Results: The best results were obtained by the PNN model. This neural network provided very high prediction ability with an accuracy of 0.892 and sensitivity of 0.975. The area under the receiver operating characteristics curve of PNN was also high, 0.818. The outcomes obtained by other classifiers were markedly worse.Conclusions: The PNN model is an effective tool for predicting 5-year overall survival in cervical cancer patients treated with radical hysterectomy. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) gene is involved in the pathogenesis of cervical cancer. However, the potential mechanism is rarely reported. Our study found that PVT1 was upregulated in cervical cancer tissue and cell lines. After transfecting PVT1 siRNA, the proliferation, migration, and invasion of cervical cancer cells were markedly decreased. miRNA expression profiles demonstrate that miR-424 was markedly downregulated in cervical cancer tissue. Bioinformatics analysis revealed that miR-424 was potentially targeted by PVT1, which was confirmed by dual-luciferase reporter assay. Pearson's correlation analysis showed that PVT1 expression was negatively related to miR-424 expression in glioma cancer tissues. Finally, lowered expression of miR-424 could recover the tumor-suppressive effects of PVT1 knockdown in cervical cancer cell lines. Our results reveal a tumorpromoting role for PVT1, acting as a competing endogenous RNA (ceRNA) or a molecular sponge in negatively modulating miR-424, which might provide a novel therapeutic target for cervical cancer. [ABSTRACT FROM AUTHOR]

Cervical cancer is among the most common cancers inflicting women worldwide. Understanding the pathological mechanisms of cervical cancer development is critical for identifying novel targets for cervical cancer treatment. MicroRNAs (miRs) have various roles in regulating cancer development. In this study, we investigated the potential role of miR-181a and its target in regulating cervical cancer development and chemotherapy resistance. The expression of miR-181a was evaluated and modulated in several human cervical cancer cell lines. The role of miR-181a in regulating cervical cancer growth and chemotherapy sensitivity was investigated in cell culture models and mouse tumor xenograft models. The target of miR-181a and its function were identified in cervical cancer models. We found a distinct expression profile for miR-181a in cervical cancer cell lines. Low expression of miR-181a was closely related to cervical cancer growth and oxaliplatin resistance. HSPA5/GRP78 was identified as a target of miR-181a in cervical cancer cells. Upregulation of GRP78 led to a high cell proliferation rate and oxaliplatin resistance in cervical cancer models. In a retrospective cervical cancer cohort, high GRP78 expression was correlated with poor survival. miR-181a suppressed cervical cancer development via downregulating GRP78. High expression of GRP78 is a tumor-promoting factor in cervical cancer and is thus a potential target for novel treatment. [ABSTRACT FROM AUTHOR]

Background: Overall, cervical cancer survival in the United States has been reported to be among the highest in the world, despite slight decreases over the last decade. Objective of the current study was to describe cervical cancer survival trends among US women and examine differences by race and stage.Methods: This study used data from the CONCORD-2 study to compare survival among women (aged 15-99 years) diagnosed in 37 states covering 80% of the US population. Survival was adjusted for background mortality (net survival) with state- and race-specific life tables and was age-standardized with the International Cancer Survival Standard weights. Five-year survival was compared by race (all races, blacks, and whites). Two time periods, 2001-2003 and 2004-2009, were considered because of changes in how the staging variable was collected.Results: From 2001 to 2009, 90,620 women were diagnosed with invasive cervical cancer. The proportion of cancers diagnosed at a regional or distant stage increased over time in most states. Overall, the 5-year survival was 63.5% in 2001-2003 and 62.8% in 2004-2009. The survival was lower for black women versus white women in both calendar periods and in most states; black women had a higher proportion of distant-stage cancers.Conclusions: The stability of the overall survival over time and the persistent differences in survival between white and black women in all US states suggest that there is a need for targeted interventions and improved access to screening, timely treatment, and follow-up care, especially among black women. Cancer 2017;123:5119-37. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cancer is the second most common cancer and the largest cancer killer among women in most developing countries including India. Although, various drugs have been developed for cervical cancer, treatment with these drugs often results in a number of undesirable side effects, toxicity and multidrug resistance (MDR). Also, the outcomes for cervical cancer patients remain poor after surgery and chemo radiation. Methods: A literature search (for drugs and delivery systems against cervical cancer) was performed on PubMed and through Google. The present review discuss about various methods including its current conventional treatment with special reference to recent advances in delivery systems encapsulating various anticancer drugs and natural plant products for targeting towards cervical cancer. The role of photothermal therapy, gene therapy and radiation therapy against cervical cancer is also discussed. Results: Systemic/targeted drug delivery systems including liposomes, nanoparticles, hydrogels, dendrimers etc. and localized drug delivery systems like cervical patches, films, rings etc. are safer than the conventional chemotherapy which has further been proved by the several drug delivery systems undergoing clinical trials. Conclusion: Novel approaches for the aggressive treatment of cervical cancer will optimistically result in decreased side effects as well as toxicity, frequency of administration of existing drugs, to overcome MDR and to increase the survival rates. [ABSTRACT FROM AUTHOR]