Early-stage Cervical Squamous Cell Carcinoma Research Articles

Deep-learning-based radiomics of intratumoral and peritumoral MRI images to predict the pathological features of adjuvant radiotherapy in early-stage cervical squamous cell carcinoma

BackgroundSurgery combined with radiotherapy substantially escalates the likelihood of encountering complications in early-stage cervical squamous cell carcinoma(ESCSCC). We aimed to investigate the feasibility of Deep-learning-based radiomics of intratumoral and peritumoral MRI images to predict the pathological features of adjuvant radiotherapy in ESCSCC and minimize the occurrence of adverse events associated with the treatment.MethodsA dataset comprising MR images was obtained from 289 patients who underwent radical hysterectomy and pelvic lymph node dissection between January 2019 and April 2022. The dataset was randomly divided into two cohorts in a 4:1 ratio.The postoperative radiotherapy options were evaluated according to the Peter/Sedlis standard. We extracted clinical features, as well as intratumoral and peritumoral radiomic features, using the least absolute shrinkage and selection operator (LASSO) regression. We constructed the Clinical Signature (Clinic_Sig), Radiomics Signature (Rad_Sig) and the Deep Transformer Learning Signature (DTL_Sig). Additionally, we fused the Rad_Sig with the DTL_Sig to create the Deep Learning Radiomic Signature (DLR_Sig). We evaluated the prediction performance of the models using the Area Under the Curve (AUC), calibration curve, and Decision Curve Analysis (DCA).ResultsThe DLR_Sig showed a high level of accuracy and predictive capability, as demonstrated by the area under the curve (AUC) of 0.98(95% CI: 0.97–0.99) for the training cohort and 0.79(95% CI: 0.67–0.90) for the test cohort. In addition, the Hosmer-Lemeshow test, which provided p-values of 0.87 for the training cohort and 0.15 for the test cohort, respectively, indicated a good fit. DeLong test showed that the predictive effectiveness of DLR_Sig was significantly better than that of the Clinic_Sig(P < 0.05 both the training and test cohorts). The calibration plot of DLR_Sig indicated excellent consistency between the actual and predicted probabilities, while the DCA curve demonstrating greater clinical utility for predicting the pathological features for adjuvant radiotherapy.ConclusionDLR_Sig based on intratumoral and peritumoral MRI images has the potential to preoperatively predict the pathological features of adjuvant radiotherapy in early-stage cervical squamous cell carcinoma (ESCSCC).

Prognostic Value of Inflammatory and Nutritional Markers for Patients With Early-Stage Poorly-to Moderately-Differentiated Cervical Squamous Cell Carcinoma.

The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), systemic inflammation response index (SIRI), and Onodera's prognostic nutritional index (OPNI) have been reported as prognostic markers for various cancers. We evaluated the prognostic value of the NLR, PLR, MLR, SII, SIRI, and OPNI for poorly-to moderately-differentiated cervical squamous cell carcinoma (CSCC). We retrospectively analyzed the cases of 109 patients with early-stage poorly-to moderately-differentiated CSCC who underwent radical surgery at our institution in 2014-2017. The optimal cutoff points for the NLR, PLR, MLR, SII, SIRI, and OPNI were determined by receiver operating characteristic curves. Overall survival was analyzed by the Kaplan-Meier method. We performed a multivariate analysis using the Cox proportional hazard regression model to determine the independent prognostic indicators for early-stage poorly-to moderately-differentiated CSCC. The appropriate cutoff points were: NLR, 1.72; PLR, 111.96; MLR, .24; SII, 566.23; SIRI, 1.38; and OPNI, 52.68. The OS of the patients with a high OPNI (P = .04), low SII (P = .03), or low SIRI (P = .01) was significantly better. The uni- and multivariate analyses identified only the OPNI as an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC (P = .04 and P = .02). The OPNI is an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC; the NLR, PLR, MLR, SII, and SIRI are not.

Prevalent distribution and survival outcome of HPV infection in patients with early-stage cervical cancer in Hangzhou, China

ObjectivesTo describe the prevalent distribution of human papilloma virus (HPV) infection in patients with early-stage cervical squamous cell carcinoma (CSCC). To provide data on high-risk HPV (HR-HPV) infection and other clinicopathological factors for their correlations with the survival of CSCC patients.MethodsA total of 1425 patients with FIGO stages IA to IIA CSCC who underwent radical surgery between September 2008 and December 2012 were enrolled in the study. The prevalent distribution of HPV infection with different patient characteristics and survivals were analyzed with or without propensity score matching (PSM).ResultsThe overall infection rate of HPV was 84.3%, including 13 carcinogenic HR-HPV genotypes and 8 low-risk HPV genotypes with infection rates of 82.6% and 5.8%, respectively. The distribution of HPV infection were proportional in patients with either different age groups or different FIGO stages. HPV16 was the dominant subtype with an infection rate of 65.1%, followed by the other top four subtypesHPV58 (8.7%), 18 (7.7%) and 52 (4.5%). χ2 analysis revealed that increased preoperative serum squamous cell carcinoma antigen levels and lymphovascular space invasion (LVSI) were statistically associated with HPV status. However, regression analyses indicated that only deep stromal invasion, LVSI and lymph node metastasis were independent prognostic factors on 5-year overall survival (OS), but not HR-HPV infection status even in the second exploratory analysis (P = 0.939) based on the PSM applied to reduce selection bias.ConclusionsThis study provided baseline data on the prevalence characteristics of HPV infections in patients with early-stage CSCC, and HR-HPV infection was not a prognosticator of 5-year OS, other than FIGO stage, LVSI and lymph node metastasis.

Para-Aortic Lymph Node Dissection for Patients with Node-Negative Cervical Squamous Cell Carcinoma: A Retrospective Cohort Study

Objective. The current guidelines for cervical cancer are uncertain regarding whether the para-aortic lymph nodes (PALNs) need to be removed. For patients with negative PALNs, whether the addition of PALN dissection (PALND) can be translated into survival benefits is unknown. Methods. The medical records of 3,995 patients with FIGO stage IB-IIA cervical squamous cell carcinoma (CSCC) who underwent abdominal radical surgery between 2006 and 2014 at our center were retrospectively reviewed. Two groups were identified: PALN-negative patients who underwent PALND (+PALND) and those who did not (−PALND). The groups were matched by propensity score matching (PSM). Survival was analyzed using the Kaplan–Meier method and the Cox proportional hazards model. Subgroups were stratified by the variables known at the time of diagnosis. Results. After PSM, 313 patients were matched to the −PALND (cohort 1) and +PALND (cohort 2) groups. Cohort 2 patients had a poorer prognosis than cohort 1 patients in terms of overall survival (OS, P = 0.014 ), and PALND was an independent prognostic factor for OS ( P = 0.021 ). There were no differences in recurrence patterns between the groups. Subgroup analysis showed that cohort 2 patients had worse OS than cohort 1 patients when they were aged ≤47 years ( P = 0.033 ), were premenopausal ( P = 0.032 ), were in stage IB ( P = 0.009 ), or had preoperative SCC-Ag&lt;6.5 ( P = 0.009 ). Conclusions. PALND negatively impacts OS in early-stage PALN-negative CSCC patients. For CSCC patients who are clinically PALN-negative, especially those who are young, are premenopausal, have tumors confined to the cervix, and have relatively low SCC-Ag values, PALND may “rub salt on the wound.”

Predicting lymph node status based on deep learning on histopathological images from primary tumor of early-stage cervical squamous cell carcinoma (080)

Objectives: To develop a new digital biomarker based on the convolutional neural network (CNN) analysis of primary tumor tissue, hence predicting lymph nodes (LNs) status in patients with early-stage cervical squamous cell carcinoma (CSCC). Methods: A total of 406 CSCC patients who underwent radical surgery between 2006 and 2014 were randomly selected, with their LNs status and hematoxylin-eosin (HE) stained primary tumor slides reviewed and confirmed by pathologists. Regions of interest (ROIs) were delineated by our pathology team. Slides were randomly divided into training, validation, and testing sets. With all Images preprocessed into patches, a CNN was trained to classify patches as LNs positive or negative. The CNN was further tested on a third independent population of 106 patients from The Cancer Genome Atlas (TCGA) database. Results: The cases included in the training set, validation set, and test set were 286, 60, and 60, respectively. Our classifier achieved an AUC of 0.86 (95% CI: 0.82-0.89) in cross-validation of slide-level LN status, 0.81 (95% CI: 0.77-0.86) on the test set, and 0.75 (95% CI: 0.71-0.82) on TCGA test set. For patients with positive LN, the digital signatures demonstrated good discrimination between patients with only pelvic LNs positive and patients with both pelvic and para-aortic LNs positive. The best performance model achieved an AUC of 0.91 (95% CI: 0.86-0.95) in the validation cohort and 0.87 (95% CI: 0.81-0.92) in the test cohort. Objectives: To develop a new digital biomarker based on the convolutional neural network (CNN) analysis of primary tumor tissue, hence predicting lymph nodes (LNs) status in patients with early-stage cervical squamous cell carcinoma (CSCC). Methods: A total of 406 CSCC patients who underwent radical surgery between 2006 and 2014 were randomly selected, with their LNs status and hematoxylin-eosin (HE) stained primary tumor slides reviewed and confirmed by pathologists. Regions of interest (ROIs) were delineated by our pathology team. Slides were randomly divided into training, validation, and testing sets. With all Images preprocessed into patches, a CNN was trained to classify patches as LNs positive or negative. The CNN was further tested on a third independent population of 106 patients from The Cancer Genome Atlas (TCGA) database. Results: The cases included in the training set, validation set, and test set were 286, 60, and 60, respectively. Our classifier achieved an AUC of 0.86 (95% CI: 0.82-0.89) in cross-validation of slide-level LN status, 0.81 (95% CI: 0.77-0.86) on the test set, and 0.75 (95% CI: 0.71-0.82) on TCGA test set. For patients with positive LN, the digital signatures demonstrated good discrimination between patients with only pelvic LNs positive and patients with both pelvic and para-aortic LNs positive. The best performance model achieved an AUC of 0.91 (95% CI: 0.86-0.95) in the validation cohort and 0.87 (95% CI: 0.81-0.92) in the test cohort.

Predictive value of preoperative serum squamous cell carcinoma antigen level for lymph node metastasis in early-stage cervical squamous cell carcinoma.

To explore the predictive value of preoperative serum squamous cell carcinoma antigen (SCC-Ag) level for lymph node metastasis (LNM), particularly, in patients surgically treated for early-stage cervical squamous cell carcinoma.We enrolled 162 patients with cervical squamous cell carcinoma stages IB to IIA following the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification. The patients had previously undergone radical surgery. Correlation of the SCC-Ag level with clinicopathological features and the predictive value of SCC-Ag for LNM were analyzed.High preoperative SCC-Ag level was correlated with FIGO stage (P = .001), tumor diameter >4 cm (P < .001), stromal infiltration (P < .001), LNM (P < .001) and lymphovascular space invasion (LVSI), (P = .045). However, it was not correlated with age, histological differentiation, parametrial involvement, and positive vaginal margin (P > .05). Univariate analysis revealed that FIGO stage (P = .015), tumor diameter (P = .044), stromal infiltration (χ2 = 10.436, P = .005), SCC-Ag ≧ 2.75 ng/mL (χ2 = 14.339, P < .001), LVSI (χ2 = 12.866, P < .001), parametrial involvement (χ2 = 13.784, P < .001) were correlated with LNM, but not with age, histological differentiation, and positive vaginal margin. Moreover, multivariate analysis demonstrated that SCC-Ag ≧2.75 ng/mL (P = .011, OR = 3.287) and LVSI (P = .009, OR = 7.559) were independent factors affecting LNM. The area under the receiver operator characteristic curve of SCC-Ag was 0.703 (P < .001), while 2.75 ng/mL was the best cutoff value for predicting LNM. The sensitivity and specificity of diagnosis were 69.4% and 65.9%, respectively.High SCC-Ag level was revealed to be an independent risk factor for the prognosis of squamous carcinoma of the cervix before an operation. Besides, SCC-Ag (2.75 ng/mL) can be utilized as a potential marker to predict LNM in early stage cervical cancer before an operation.

Prediction of lymphovascular space invasion using a combination of tenascin-C, cox-2, and PET/CT radiomics in patients with early-stage cervical squamous cell carcinoma

BackgroundLymphovascular space invasion is an independent prognostic factor in early-stage cervical cancer. However, there is a lack of non-invasive methods to detect lymphovascular space invasion. Some researchers found that Tenascin-C and Cyclooxygenase-2 was correlated with lymphovascular space invasion. Radiomics has been studied as an emerging tool for distinguishing tumor pathology stage, evaluating treatment response, and predicting prognosis. This study aimed to establish a machine learning model that combines radiomics based on PET imaging with tenascin-C (TNC) and cyclooxygenase-2 (COX-2) for predicting lymphovascular space invasion (LVSI) in patients with early-stage cervical cancer.MethodsOne hundred and twelve patients with early-stage cervical squamous cell carcinoma who underwent PET/CT examination were retrospectively analyzed. Four hundred one radiomics features based on PET/CT images were extracted and integrated into radiomics score (Rad-score). Immunohistochemical analysis was performed to evaluate TNC and COX-2 expression. Mann-Whitney U test was used to distinguish differences in the Rad-score, TNC, and COX-2 between LVSI and non-LVSI groups. The correlations of characteristics were tested by Spearman analysis. Machine learning models including radiomics model, protein model and combined model were established by logistic regression algorithm and evaluated by ROC curve. Pairwise comparisons of ROC curves were tested by DeLong test.ResultsThe Rad-score of patients with LVSI was significantly higher than those without. A significant correlation was shown between LVSI and Rad-score (r = 0.631, p < 0.001). TNC was correlated to both the Rad-score (r = 0.244, p = 0.024) and COX-2 (r = 0.227, p = 0.036). The radiomics model had the best predictive performance among all models in training and external dataset (AUCs: 0.914, 0.806, respectively, p < 0.001). However, in testing dataset, the combined model had better efficiency for predicting LVSI than other models (AUCs: 0.801 vs. 0.756 and 0.801 vs. 0.631, respectively).ConclusionThe machine learning model of the combination of PET radiomics with COX-2 and TNC provides a new tool for detecting LVSI in patients with early-stage cervical cancer. In the future, multicentric studies on larger sample of patients will be used to test the model.Trial registrationThis is a retrospective study and there is no experimental intervention on human participants. The Ethics Committee has confirmed that retrospectively registered is not required.

A novel prognostic prediction model based on seven immune-related RNAs for predicting overall survival of patients in early cervical squamous cell carcinoma

BackgroundIn this study, we aimed to mine immune-related RNAs expressed in early cervical squamous cell carcinoma to construct prognostic prediction models.MethodsThe RNA sequencing data of 309 cervical squamous cell carcinoma (CSCC) cases, including data of individuals with available clinical information, were obtained from The Cancer Genome Atlas (TCGA) database. We included 181 early-stage CSCC tumor samples with clinical survival and prognosis information (training dataset). Then, we downloaded the GSE44001 gene expression profile data from the National Center for Biotechnology Information Gene Expression Omnibus (validation dataset). Gene ontology annotation and the Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to analyze the biological functions of differentially expressed immune-related genes (DEIRGs). We established protein–protein interactions and competing endogenous RNA networks using Cytoscape. Using the Kaplan–Meier method, we evaluated the association between the high- and low-risk groups and the actual survival and prognosis information. Our univariate and multivariate Cox regression analyses screened for independent prognostic factors.ResultsWe identified seven prognosis-related signature genes (RBAKDN, CXCL2, ZAP70, CLEC2D, CD27, KLRB1, VCAM1), the expression of which was markedly associated with overall survival (OS) in CSCC patients. Also, the risk score of the seven-gene signature discripted superior ability to categorize CSCC patients into high-risk and low-risk groups, with a observablydifferent OS in the training and validation datasets. We screened two independent prognostic factors (Pathologic N and prognostic score model status) that correlated significantly by univariate and multivariate Cox regression analyses in the TCGA dataset. To further explore the potential mechanism of immune-related genes, we observed associated essential high-risk genes with a cytokine–cytokine receptor interaction.ConclusionsThis study established an immune-related RNA signature, which provided a reliable prognostic tool and may be of great significance for determining immune-related biomarkers in CSCC.

A preoperative radiomics model for the identification of lymph node metastasis in patients with early-stage cervical squamous cell carcinoma.

To develop and validate a radiomics model for preoperative identification of lymph node metastasis (LNM) in patients with early-stage cervical squamous cell carcinoma (CSCC). Total of 190 eligible patients were randomly divided into training (n = 100) and validation (n = 90) cohorts. Handcrafted features and deep-learning features were extracted from T2W fat suppression images. The minimum redundancy maximum relevance algorithm and LASSO regression with 10-fold cross-validation were used for key features selection. A radiomics model that incorporated the handcrafted-signature, deep-signature, and squamous cell carcinoma antigen (SCC-Ag) levels was developed by logistic regression. The model performance was assessed and validated with respect to its calibration, discrimination, and clinical usefulness. Three handcrafted features and three deep-learning features were selected and used to build handcrafted- and deep-signature. The model, which incorporated the handcrafted-signature, deep-signature, and SCC-Ag, showed satisfactory calibration and discrimination in the training cohort (AUC: 0.852, 95% CI: 0.761-0.943) and the validation cohort (AUC: 0.815, 95% CI: 0.711-0.919). Decision curve analysis indicated the clinical usefulness of the radiomics model. The radiomics model yielded greater AUCs than either the radiomics signature (AUC = 0.806 and 0.779, respectively) or the SCC-Ag (AUC = 0.735 and 0.688, respectively) alone in both the training and validation cohorts. The presented radiomics model can be used for preoperative identification of LNM in patients with early-stage CSCC. Its performance outperforms that of SCC-Ag level analysis alone. A radiomics model incorporated radiomics signature and SCC-Ag levels demonstrated good performance in identifying LNM in patients with early-stage CSCC.

The outcomes and quality of life of young patients undergoing adjuvant radiotherapy versus non-radiotherapy following surgery treating early FIGO stage cervical squamous cell cancer in southwestern China

Background: The incidence of cervical cancer in young women is rising, and squamous cell carcinoma makes up a great percentage of the histological types. The presence of aggressive pathologic risk factors following patients’ primary surgery may warrant the use of adjuvant radiotherapy. It is important to weigh up the risks and benefits of using adjuvant radiotherapy for each young patient so as to maximize their prognosis while minimizing the treatment-related morbidity. Methods: A retrospective study was performed. It consisted of 97 patients under 35 years old who were diagnosed with cervical squamous cell carcinoma and underwent treatment at West China Second University Hospital between December 2009 and January 2014. Five-year follow-up, prognostic risks, long-term radiation toxicity, female sexual function, and quality of life were investigated. Results: Adjuvant radiotherapy did improve the prognosis of young patients with lymph node metastases. However, there were few significant differences in progress-free survival and overall survival for the young patients without lymph node metastases following adjuvant radiotherapy. Besides, young patients who took radiotherapy exhibited greater intestinal dysfunction, more severe lower extremities edema, greater sexual dysfunction, and worse long-term quality of life. Conclusion: Young patients with early-stage cervical squamous cell carcinoma without lymph node metastases who have undergone the primary surgery should be counseled in detail before the decision to use adjuvant radiotherapy can be made. The counseling should emphasize not only the benefit that local recurrence rates can be reduced, but also the risks that treatment-related side effects could increase and lower QoL could occur.

LncRNA NKILA inhibits the proliferation and promotes the apoptosis of CSCC cells by downregulating miRNA-21.

Long noncoding RNA (lncRNA) NKILA has been well studied in several types of human tumors as a tumor suppressor, while its involvement in cervical squamous cell carcinoma (CSCC) remains unclear. In our studies, we found that serum NKILA was at lower levels and serum microRNA-21 (miRNA-21) was at higher levels in patients with early stage CSCC than in the healthy female. Altered expression of NKILA and miRNA-21 can effectively separate patients with CSCC at an early stage from healthy controls. Serum levels of NKILA were significantly and negatively correlated with miRNA-21 in patients with CSCC but not in normal controls. Overexpression of NKILA mediated the inhibited expression of miRNA-21 in CSCC cells, but mimic transfection of miRNA-21 did not significantly change the expression level of NKILA. Overexpression of NKILA repressed the proliferation and promoted the apoptosis of CSCC cells, while miRNA-21 showed opposite functions. In addition, miRNA-21 mimic transfection reduced the effects of NKILA on CSCC cells. Collectively, lncRNA NKILA could repress the proliferation and promote the apoptosis of CSCC cells by downregulating miRNA-21.

Laparoscopic surgery for early cervical squamous cell carcinoma and its effect on the micrometastasis of cancer cells.

The aim of this study was to evaluate the effect of laparoscopic radical hysterectomy on expressions of circulating tumor cells (CTCs) of cytokeratin 19 (CK19), cytokeratin 20 (CK20), and squamous cell carcinoma antigen (SCC-Ag) mRNA.We collect 78 patients with stage IA2-IIA1 cervical cancer who underwent radical hysterectomy by laparotomy or laparoscopy in our study, and 34 uterine fibroids patients and 32 healthy subjects were recruited as the positive control group and negative control group, respectively. Blood samples were taken from early-stage primary cervical squamous cell carcinoma patients. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to amplify peripheral blood CK19, CK20 and SCC-Ag from total RNA. We measured the expression of CK19, CK20, and SCC-Ag before laparoscopic radical hysterectomy, 24 hours and 30 days after surgery. Meanwhile, the expression of these markers was compared between laparoscopic and laparotomy groups.The expressions of CK19, CK20, and SCC-Ag in the experimental group before surgery were (0.0035 ± 0.0018), (1.06 ± 0.49), and (1.48 ± 0.46), respectively, and the positive rates were 32.1%, 33.3%, and 35.9%, respectively. The expression levels of CK19, CK20, and SCC-Ag in the experimental group before surgery was significantly higher than the positive and negative control groups, and there were no significant differences between the positive and negative control groups. The expressions and positive rates of CK19, CK20, and SCC-Ag before laparoscopic radical hysterectomy were significantly lower than the stage at 24 hours after surgery (P < .05), but higher than the stage at 30 days after surgery (P > .05). There were no significant differences in CK19, CK20, and SCC-Ag expressions before surgery, 24 hours and 30 days after surgery between laparoscopic group and laparotomy group (P > .05).Both laparotomy and laparoscopic radical mastectomy tend to increase the expression of CTCs in peripheral blood, and the expressions have no differences between these 2 groups. So, the use of CK19, CK20, and SCC-Ag expression levels from peripheral blood from early stage cervical cancer radical patients before hysterectomy can aid to overcome the lack of radiographic examination and tumor markers measurement, and provide clues for postoperative treatment and prognosis determination.

Value of [18F]FDG PET radiomic features and VEGF expression in predicting pelvic lymphatic metastasis and their potential relationship in early-stage cervical squamous cell carcinoma

PurposeThe purpose of this study was to explore the value of 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) radiomic features combined with vascular endothelial growth factor (VEGF) expression in predicting pelvic lymphatic metastasis in patients with early-stage cervical squamous cell carcinoma and the added value of radiomic features in predicting VEGF expression. Materials and methodsNinety-four newly diagnosed cervical squamous cell carcinoma patients (training dataset: n = 64, validation cohort: n = 30) in stage Ia to IIa, according to the International Federation of Gynecology and Obstetrics (FIGO) staging system, who underwent [18F]FDG PET/CT were retrospectively analyzed. Radiomic features of the [18F]FDG PET scans were extracted, and the value of the lymph node sizes, metabolic parameters (both tumor and lymph nodes), radiomic features and VEGF expression level in predicting lymphatic metastasis were evaluated by receiver operating characteristics curves (ROC) and were compared using DeLong test. Moreover, we studied the associations between the [18F]FDG PET radiomic features and VEGF expression. ResultsTotal lesion glycolysis (TLG) and the expression of VEGF were significantly higher in subjects with lymphatic metastasis than in those without. The homogeneity feature derived from the histogram, the skewness, had a certain value in predicting lymphatic metastasis (AUC = 0.803 in training dataset, P < 0.05, 95% CI 0.684, 0.892; AUC = 0.757 in validation dataset, P < 0.05, 95% CI 0.545, 0.904). Additionally, the combination of this radiomic feature and VEGF expression had a significantly superior predictive value (AUC = 0.878, P < 0.05, 95% CI 0.772– 0.947), compared to that of the conventional parameters. Moreover, 26 radiomic features derived from the histogram and GLCM features correlated with VEGF expression. ConclusionsIn patients with early-stage cervical squamous cell carcinoma, PLN metastasis can be predicted by TLG and the textural feature of homogeneity. Radiomic features in combination with the VEGF expression level improved the prediction accuracy. In addition, some features derived from the histogram and gray-level co-occurrence matrices (GLCM) may have a certain value in predicting the VEGF expression level.

Correlation Between Squamous Cell Carcinoma Antigen Level and the Clinicopathological Features of Early-Stage Cervical Squamous Cell Carcinoma and the Predictive Value of Squamous Cell Carcinoma Antigen Combined With Computed Tomography Scan for Lymph Node Metastasis.

The aim of this study was to analyze the relationship between serum squamous cell carcinoma antigen (SCC-Ag) and the clinicopathological features of cervical squamous cell carcinoma. The value of SCC-Ag and computed tomography (CT) for predicting lymph node metastasis (LNM) was evaluated. A total of 197 patients with International Federation of Gynecology and Obstetrics stages IB to IIA cervical squamous cell carcinoma who underwent radical surgery were enrolled in this study. The SCC-Ag was measured, and CT scans were used for the preoperative assessment of lymph node status. Increased preoperative SCC-Ag levels were associated with International Federation of Gynecology and Obstetrics stage (P = 0.001), tumor diameter of greater than 4 cm (P < 0.001), lymphovascular invasion (P = 0.001), LNM (P < 0.001), and greater than one half stromal infiltration (P < 0.001). Multivariate analysis identified LNM (P < 0.001, odds ratio [OR] = 4.399), tumor diameter of greater than >4 cm (P = 0.001, OR = 4.019), and greater than one half stromal infiltration (P = 0.002, OR = 3.680) as independent factors affecting SCC-Ag greater than or equal to 2.35 ng/mL. In the analysis of LNM, SCC-Ag greater than or equal to 2.35 ng/mL (P < 0.001, OR = 4.825) was an independent factor for LNM. The area under the receiver operator characteristic curve (AUC) of SCC-Ag was 0.763 for all patients, and 0.805 and 0.530 for IB1 + IIA1 and IB2 + IIA2 patients, respectively; 2.35 ng/mL was the optimum cutoff for predicting LNM. The combination of CT and SCC-Ag showed a sensitivity and specificity of 82.9% and 66% in parallel tests, and 29.8% and 93.3% in serial tests, respectively. The increase of SCC-Ag level in the preoperative phase means that there may be a pathological risk factor for postoperative outcomes. The SCC-Ag (≥2.35 ng/mL) may be a useful marker for predicting LNM of cervical cancer, especially in stages IB1 and IIA1, and the combination of SCC-Ag and CT may help identify patients with LNM to provide them with the most appropriate therapeutic approach.

Characterization of the microRNA profile in early-stage cervical squamous cell carcinoma by next-generation sequencing.

Squamous cell carcinoma (SCC) is histologically the most prominent type of cervical cancer. There is accumulating evidence suggesting that microRNAs (miRNAs) play important regulatory roles in the biological processes of cervical squamous cell carcinoma (CSCC). Deciphering the miRNA regulatory network in CSCC could deepen our understanding at the molecular level of CSCC initiation and progression. In the present study, we performed next‑generation sequencing (NGS) to profile miRNA expression in 3pairs of early-stage CSCC samples. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify primary findings in another 20pairs of CSCC samples. We identified 37known miRNAs that exhibited significant alterations in expression (2-fold change or greater), among which 8miRNAs were upregulated and 29miRNAs were downregulated. Nine of these miRNAs were selected for further qRT-PCR validation. A novel miRNA candidate was also reported for the first time in the present study to be upregulated. The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that its target genes were involved in MAPK, calcium and adherent junction signaling pathways. The present study systematically characterized the miRNA expression variation in early-stage CSCC and provides novel biomarkers for diagnosis and treatment as well as an opportunity for further investigation of the molecular mechanisms underlying the pathogenesis and development of CSCC.

Early-stage node negative cervical adenocarcinoma and squamous cell carcinoma show similar survival outcomes after hysterectomy: a population-based study.

ObjectiveTo investigate the clinicopathological features and outcomes between node-negative, early-stage cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) after hysterectomy.MethodsPatients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stages I–IIA cervical SCC and AC between 1988 and 2013 were retrospectively reviewed using the Surveillance, Epidemiology, and End Results database. We used propensity score-matching to balance patient baseline characteristics. Univariate and multivariate Cox regression analyses were used for prognostic analyses of cause-specific survival (CSS) and overall survival (OS).ResultsA total of 9,858 patients were identified, comprising 6,117 patients (62.1%) and 3,741 (37.9%) patients with cervical SCC and AC, respectively. Compared with cervical SCC, cervical AC cases were more likely to be younger, diagnosed after 2000, white, and have well-differentiated and FIGO stage IB1 disease. For SCC and AC, the 10-year CSS rates were 93.4% and 94.7%, respectively (p=0.011), and the 10-year OS rates were 89.6% and 92.2%, respectively (p<0.001). Multivariate analysis revealed that age, ethnicity, tumor grade, and FIGO stage were independent prognostic factors of CSS and OS, but that histologic subtype was not associated with CSS and OS. In the propensity score-matched patient population, univariate and multivariate analyses also showed that histologic subtype was not associated with survival outcomes.ConclusionCervical AC has equivalent survival to cervical SCC in node-negative, early-stage disease after hysterectomy and lymphadenectomy.

High Expression of KIF20A Is Associated with Poor Overall Survival and Tumor Progression in Early-Stage Cervical Squamous Cell Carcinoma.

BackgroundThe kinesin family member 20a (KIF20A) protein has been implicated in the development and progression of many human cancers; however, its precise function and role in cervical cancer remain largely unclear. This study aimed to investigate the expression profile and prognostic value of KIF20A in patients with early-stage cervical squamous cell carcinoma.MethodsWe examined the mRNA and protein levels of KIF20A in eight cervical cancer cell lines and eight paired cervical cancer samples, compared with normal cervical epithelial cells and adjacent normal cervical tissues, respectively. Immunohistochemistry was performed to detect the expression of KIF20A in paraffin-embedded specimens from 169 early-stage cervical squamous cell carcinoma patients. Statistical analyses were applied to analyze the association between KIF20A expression and clinical variables, as well with patient survival.ResultsThe mRNA and protein expression levels of KIF20A were significantly elevated in cervical cancer cell lines and lesions compared with normal cells and corresponding normal tissues (P < 0.05). Immunohistochemistry analysis in 169 cervical cancer cases revealed that increased KIF20A expression was strongly associated with human papillomavirus (HPV) infection (P = 0.008), clinical stage (P = 0.001), tumor recurrence (P = 0.016), vital status (P < 0.001), the property of the surgical margin (P = 0.032), the lymphovascular space involvement (P = 0.014), and pelvic lymph node metastasis (P = 0.001). The overall survival and disease-free survival of patients with high levels of KIF20A expression were significantly poorer than those with low KIF20A expression. KIF20A was an independent survival prognostic factor, as evidenced by univariate and multivariate analysis.ConclusionsOur results illustrate that elevated KIF20A expression correlates with HPV infection, clinical stage, tumor recurrence, lymphovascular space involvement, pelvic lymph node metastasis, and poor outcome in early-stage cervical squamous cell carcinoma patients. KIF20A aberrant expression is a novel independent unfavorable prognostic factor and may present a potential therapeutic target for cervical cancer.

Postoperative adjuvant chemotherapy combined with intracavitary brachytherapy in early-stage cervical cancer patients with intermediate risk factors.

ObjectiveTo investigate the impact of postoperative adjuvant therapy on survival of patients with intermediate risk early-stage cervical squamous cell carcinoma.MethodsA total of 133 consecutive patients with intermediate risk early-stage cervical squamous cell carcinoma treated at Shandong Cancer Hospital and Institute from February 2010 to March 2014 were enrolled in our study. All patients received adjuvant therapy and were subdivided into three groups: pelvic radiotherapy (RT; N=42), adjuvant chemotherapy + intracavitary radiotherapy (CT+ICRT; N=47), or concurrent chemoradiation (CCRT; N=44). Disease-free survival (DFS) and therapeutic complications were evaluated.ResultsThere were no significant differences in DFS for patients treated with RT, CT+ICRT, and CCRT (P>0.05) with 3-year rates of 94.0%, 93.4%, and 97.6%, respectively. Frequencies of grade III–IV acute toxicities were higher in patients treated with CCRT (34.1%) than those treated with RT (9.5%) or CT+ICRT (16.7%; P<0.05), with no significant differences observed between RT and CT+ICRT groups (P>0.05). Grade I–II late toxicities were higher in CCRT (25%), followed by RT (19.0%), and finally, the CT+ICRT group (4.3%; P<0.05); with no significant differences observed between CCRT and RT groups (P>0.05).ConclusionTreatment with CT+ICRT or RT resulted in the equivalent of 3-year DFS compared to CCRT, but fewer therapeutic complications were observed with CT for patients with intermediate risk early-stage cervical squamous cell carcinoma.

TRPV6 is a prognostic marker in early-stage cervical squamous cell carcinoma.

Transient receptor potential vanilloid 6 (TRPV6) has been shown to promote caner proliferation in several solid tumors, leading to unfavorable clinical outcomes. Our study aimed to elucidate the clinical significance of TRPV6 in patients with early-stage cervical squamous cell carcinoma (CSCC). The mRNA expression of TRPV6 was measured in 12 paired early-stage CSCC specimens and six cervical carcinoma cell lines using quantitative real-time PCR (qRT-PCR). Western blotting and immunohistochemistry (IHC) were employed to examine the protein expression level of TRPV6 in four paired specimens, 175 paraffin-embedded early-stage CSCC specimens, and 50 normal cervical tissues (NCTs), respectively. Statistical analyses were performed to evaluate the clinical significance of TRPV6 expression. The expressions of TRPV6 mRNA and protein were both significantly downregulated in early-stage CSCC tissues and cervical cancer cell lines. IHC analyses revealed that TRPV6 was downregulated in 136 (77.7%) of 175 early-stage CSCC specimens. Moreover, TRPV6 expression in early-stage CSCC was significantly correlated with the tumor stage (P<0.001), tumor growth type (P<0.001), tumor size (P=0.008), and differentiation grade (P=0.003). The early-stage CSCC patients with a low TRPV6 expression level had a short progress-free survival (PFS) and overall survival (OS) duration. Univariate and multivariate analyses identified TRPV6 as an independent prognostic factor for early-stage CSCC patients' survival. We demonstrated that TRPV6 was downregulated in CSCC, which was correlated with unfavorable survival outcomes of early-stage CSCC patients. TRPV6 may be used as a novel prognostic marker for early-stage CSCC.

Expression and prognostic significance of TAp73 and ΔNp73 in FIGO stage I-II cervical squamous cell carcinoma.

The purpose of the present study was to investigate the expression of TAp73 and ΔNp73 in cervical squamous cancer cells, and to evaluate the prognostic significance of TAp73 and ΔNp73 expression in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II cervical squamous cell carcinoma (SCC). The immunohistochemical expression of TAp73 and ΔNp73 was evaluated in 59 FIGO stage I-II cervical SCC tumor samples. Correlations with clinicopathological characteristics were determined by χ2 test. The prognostic impact of TAp73 and ΔNp73 expression with regard to overall survival (OS) was determined by the Kaplan-Meier method. High TAp73 and ΔNp73 expression was detected in 79.7% (47/59) and 76.3% (45/59) of patients, respectively. The expression of TAp73 and ΔNp73 was not associated with age, FIGO stage, pathological differentiation or lymph node metastasis. The 3-year OS rates associated with low and high TAp73 expression were 75.0 and 83.0%, respectively (χ2=0.33; P=0.568), whereas those associated with low and high ΔNp73 expression were 100.0 and 75.6%, respectively (χ2=3.90; P=0.048). High expression levels of TAp73 and ΔNp73 were frequently observed in the cervical squamous cancer cells. Overall, high expression levels of ΔNp73 may indicate an unfavorable prognosis in patients with early-stage cervical SCC.