Squamous Cell Cervical Cancer Research Articles

Oncogenic driver FGFR3-TACC3 requires five coiled-coil heptads for activation and disulfide bond formation for stability.

FGFR3-TACC3 represents an oncogenic fusion protein frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Various exon breakpoints of FGFR3-TACC3 have been identified in cancers; these were analyzed to determine the minimum contribution of TACC3 for activation of the FGFR3-TACC3 fusion protein. While TACC3 exons 11 and 12 are dispensable for activity, our results show that FGFR3-TACC3 requires exons 13-16 for biological activity. A detailed analysis of exon 13, which consists of 8 heptads forming a coiled coil, further defined the minimal region for biological activity as consisting of 5 heptads from exon 13, in addition to exons 14-16. These conclusions were supported by transformation assays of biological activity, examination of MAPK pathway activation, analysis of disulfide-bonded FGFR3-TACC3, and by examination of the Endoglycosidase H-resistant portion of FGFR3-TACC3. These results demonstrate that clinically identified FGFR3-TACC3 fusion proteins differ in their biological activity, depending upon the specific breakpoint. This study further suggests the TACC3 dimerization domain of FGFR3-TACC3 as a novel target in treating FGFR translocation driven cancers.

RAIDS atlas of significant genetic and protein biomarkers in cervical cancer.

Loss of function in epigenetic acting genes together with driver alterations in the PIK3CA pathway have been shown significantly associated with poor outcome in cervical squamous cell cancer. More recently, a CoxBoost analysis identified 16 gene alterations and 30 high level activated proteins to be of high interest, due to their association with either good or bad outcome, in the context of treatment received by chemoradiation. The objectives here were to review and confirm the significance of these molecular alterations as suggested by literature reports and to pinpoint alternate treatments options for poor-responders to chemoradiation.

A preoperative prediction of lymph node metastasis in early cervical squamous cell cancer with hematologica - based model.

Background: This study aimed to construct a preoperative model predicting lymph node metastasis (LNM) in IB1-IIA2 stage cervical squamous cell cancer (CSCC) based on hematological indexes. Merhods: Between February 2011 and February 2022, 463 patients with IB1-IIA2 stage CSCC underwent radical resection. Patients were allocated to either a model-development cohort (n=337) or a validation cohort (n=126). The final model was determined by comparing different methods of variable selection, and then its discrimination and calibration metrics were evaluated. A predicted probability of LNM < 5% was defined as low risk. ROC curves were used to define high risk. Results: Age, lactate dehydrogenase level, FIGO stage, squamous cell carcinoma antigen, cancer antigen 125, and cancer antigen 199 were identified as critical factors for the construction of the model. The model demonstrated good discrimination and calibration (concordance index, 0.761; 95% confidence interval, 0.666-0.884). In the validation cohort the discrimination accuracy was 0.821 (95% confidence interval, 0.714 - 0.927). In the model-development cohort, 11.9% were classified as low risk with a negative predictive value of 95.0%, and 24.9% were classified as high risk with a positive predictive value of 39.3%. Conclusion: A predictive model was developed and validated for LNM in IB1-IIA2 stage CSCC. The model will assist physicians in appraising the risk of LNM in preoperative patients and could aid in patient counseling and individualized clinical decision-making.

Predictive markers of immunotherapy in cervical cancer

Study of PD-L1 expression in squamous and adenosquamous cell cervical cancer (CC) by immunohistochemical (IHC) method, assessment of the relationship between PD-L1 tumor status and its clinical and morphological characteristics, TILs, MSI/dMMR, and HPV tumor status. Surgical material was obtained from 41 patients with CC, on which the expression of PD-L1, proteins of the MMR system and p16 was studied by the IHC method, the TILs index was determined. Positive PD-L1 status was found in 51.2% of the studied CC samples. In the study sample, the level of PD-L1 expression depended on the severity of lymphoid infiltration of the tumor (p=0.038), it was shown that a positive PD-L1 status of CC can be expected with a TILs value greater than or equal to 50%. The age of the patients, the histological variant of the tumor, the pT and pN stage, the presence of lymphovascular invasion, and the HPV status did not statistically significantly affect the level of PD-L1 expression, however, there was an association between the PD-L1 status and the grade of CC malignancy (p=0.027). The presence of the MSI/dMMR phenomenon was detected in a small percentage of carcinomas (4.9%), the PD-L1 status of these tumors was determined as positive. A positive PD-L1 status is determined in a significant number of cases of CC, regardless of most of the studied clinical and morphological characteristics; there is a statistically significant relationship between PD-L1 expression and the degree of tumor differentiation and TILs. It has been shown that CC with the MSI/dMMR phenomenon is characterized by a positive PD-L1 status. The authors consider it necessary to study the expression of PD-L1 in patients with cervical carcinomas in order to determine the possibility of prescribing personalized therapy with immune checkpoint inhibitors.

L1CAM Is Not a Predictive Factor in Early-stage Squamous-cell Cervical Cancer.

Our study aimed to assess expression of L1 cell adhesion molecule (L1CAM) in early-stage cervical squamous-cell cancer as a prognostic factor. This retrospective, single-institution study included 154 patients who underwent radical hysterectomy for early-stage squamous cell cervical cancer between 2007 and 2017. Tumor samples from 154 patients were available for L1CAM analysis by immunohistochemistry. Among all patients, radical abdominal hysterectomy was performed in 144 cases. L1CAM expression was positive in 24 tumors (15.6%) of the whole group. In relation to the grade of differentiation and the presence of lymphovascular invasion, L1CAM expression did not show an association (p=0.154 and p=0.306, respectively). The disease-free interval and overall survival also did not significantly differ between L1CAM-positive and L1CAM-negative cases (p=0.427 and p=0.240, respectively). For histopathological characteristics, L1CAM-positive cases had a significantly higher median tumor size (p=0.015). Even in the selected group of 115 cases without nodal infiltration, L1CAM status had no effect on the relapse rate during follow-up. Our study did not confirm the results of previous studies showing L1CAM expression to be a negative prognostic factor in cervical cancer. In our study, increased L1CAM expression in early-stage squamous-cell cervical cancer was not associated with adverse prognosis regarding disease recurrence, disease-free survival, nor overall survival. L1CAM expression was correlated only with the size of the tumor.

Fe(II) complexes of 2,2':6',2''-terpyridine ligands functionalized with substituted-phenyl groups: synthesis, crystal structures and anticancer potential.

With the aim of developing potential anticancer drug candidates, a series of Fe(II) complexes were synthesized using nine 2,2':6',2''-terpyridine ligands functionalized with substituted-phenyl groups, and their biological activities were systematically investigated. Their bis-terpyridine sandwich-like structures were determined by single crystal X-ray crystallography. In vitro antiproliferative experiments based on three human cancer cell lines, including human hepatoma cancer cell line (Bel-7402), human esophageal cancer cell line (Eca-109), and human cervical squamous cancer cell line (SiHa), indicate the high antiproliferation activities of these complexes compared with commercial cisplatin. And their toxicity to normal cells was estimated based on human normal hepatocyte (HL-7702) cell line. In particular, when the phenyl in terpyridine ligand was modified by a carboxyl group, the corresponding complex 3 exhibited much higher antiproliferation to cancer Bel-7402 cells (IC50 = 3.653 μmol L-1) than cisplatin and low toxicity to normal HL-7702 cells (IC50 = 99.92 μmol L-1), implying a significant selectivity for 3 in killing hepatoma cancer cells. Combined with the fact that iron element is more accessible than platin, this series of Fe(II) complexes comprises potential candidates for anticancer drugs with specific inhibition of hepatoma cancer. UV titration experiments and circular dichroism (CD) showed a strong binding affinity between these nine complexes and CT-DNA. However, molecular docking simulation revealed the competitive binding of DNA and protein to these complexes. Further, the interactions between these complexes and bovine serum albumin (BSA) have been studied by fluorescence titration and CD spectroscopy.

Prognostic significance of albumin and globulin levels in cervical cancer patients treated with chemoradiotherapy

ObjectiveAlbumin-globulin ratio or albumin-globulin score predict survival in many cancers, but there are few data on cervical cancer patients. This study examined whether pre-treatment albumin and globulin levels, as well...

Laparoscopic Abdominal Cerclage after Prior Radical Trachelectomy

<h3>Study Objective</h3> To present a case and surgical video of laparoscopic abdominal cerclage placement after prior radical trachelectomy and demonstrate techniques in overcoming challenging dissections and an alternative surgical technique in placement of cerclage. <h3>Design</h3> Case report and surgical video. <h3>Setting</h3> In the operating room with a patient in dorsal lithotomy position with both arms tucked. A 10mm port was placed at the umbilicus and 3 additional 5mm ports were placed in the right and left lower quadrant and suprapubic region. A uterine manipulator, flexible laparoscopic, and bipolar sealing device were used. <h3>Patients or Participants</h3> One patient. <h3>Interventions</h3> A 34yo P2 with prior surgical history of exploratory laparotomy, radical trachelectomy, sentinel lymph node mapping, pelvic lymphadenectomy for stage 1B1 cervical squamous cell cancer. She had been disease free for two years and she had erosion of her vaginal cerclage that had been placed at the time of her original surgery. She had two prior cesarean deliveries prior to her cervical cancer diagnosis and desired future fertility. She underwent a laparoscopic abdominal cerclage with cystoscopy and ureteral catheter placement. <h3>Measurements and Main Results</h3> Laparoscopic placement of abdominal cerclage was successful. Surgical techniques in navigating difficult dissections are reviewed in the video. In the absence of a cervicouterine junction, placement a 5mm Mersilene tape cerclage at the neo-cervical region was successful. There were no intra or post-operative complications. Patient had a good surgical recovery. <h3>Conclusion</h3> This video demonstrates challenges in placement of an abdominal cerclage following a radical trachelectomy due to distortion of anatomy and dense post-surgical adhesions. The video demonstrates that laparoscopic placement at the neo-cervical junction can be accomplished successfully and safely.

Role of the Radiosensitizing Effect of Metformin Added to Concomitant Chemoradiotherapy with Cisplatin in Cervical Squamous Cell Cancer Cell Lines

<h3>Purpose/Objective(s)</h3> The aim of this study is to investigate the radiosensitizing effect of metformin per se and combined with cisplatin in human cervical cancer cell lines (HeLa) and explore how radiosensitizing effect changes with activation/inhibition of adenosine monophosphate-activated protein kinase (AMPK). <h3>Materials/Methods</h3> AMPK gene expressions were compared between normal cervix and cervical cancer tissues using GSE9750 and GSE63514 databases. HeLa cell lines were exposed to 0, 2, 4, 6, and 8 Gy ionizing radiation (IR), 150 uM metformin, 1 uM cisplatin, 100 uM A769662 (AMPK activator), and 0.5 uM dorsomorfin (AMPK inhibitor) or combination of those drugs with cisplatin and IR. Cell proliferation, western blotting, and flow cytometry were used to evaluate the treatment effects. <h3>Results</h3> AMPK gene (PRKAA1) expressions were significantly higher in cervical cancer tissues than normal cervical tissue. Metformin and cisplatin per se did not decrease the cell proliferation without IR, but metformin, when combined with cisplatin, potentiated cisplatin cytotoxicity. Although the radiosensitizing effects of metformin and cisplatin per se were present which is more apparent in high (4, 6, and 8 Gy) IR doses, metformin-cisplatin combinations did not increase the radiosensitivity of cisplatin in any IR doses. Dorsomorfin per se significantly decreased cell proliferation and when combined with cisplatin potentiated radiosensitizing effect of cisplatin in 0, 2, 4, and 6 Gy IR doses, and this effect was confirmed with an increase in p-53BP1 and ERCC1 protein levels. Thus, dorsomorfin was found to be a better radiosensitizing agent than A769662 and metformin. Administration of A769662 one day prior to cisplatin treatment resulted in increased AMPK level that produced resistance to cisplatin, but this effect was not observed in HeLa cells when concomitantly treated with A769662 and cisplatin. The radiosensitizing effects of metformin, cisplatin, A769662, and dorsomorfin have been confirmed with the analysis of DNA damage proteins, damage repair proteins and evaluation of cell cycle arrest. <h3>Conclusion</h3> Modulation of AMPK may have a role in cervical cancer treatment. Increased AMPK levels result in higher sensitivity to IR but cause resistance to cisplatin. Dorsomorfin is a potent radiosensitizing agent and further clinical trials should be performed. The use of metformin alone may be an option as a radiosensitizer during high dose IR (e.g., intracavitary brachytherapy) in clinical practice and further clinical trials should be performed.

MRI-based radiomics for pretreatment prediction of response to concurrent chemoradiotherapy in locally advanced cervical squamous cell cancer.

To investigate the value of magnetic resonance imaging (MRI)-based radiomics in predicting the treatment response to concurrent chemoradiotherapy (CCRT) in patients with locally advanced cervical squamous cell cancer (LACSC). In total, 198 patients (training: n = 138; testing: n = 60) with LACSC treated with CCRT between January 2014 and December 2019 were retrospectively enrolled in this study. Responses were evaluated by MRI and clinical data performed at one month after completion of CCRT according to RECIST standards, and patients were divided into the residual group and nonresidual group. Overall, 200 radiomics features were extracted from T2-weighted imaging and apparent diffusion coefficient maps. The radiomics score (Rad-score) was constructed with a feature selection strategy. Logistic regression analysis was used for multivariate analysis of radiomics features and clinical variables. The performance of all models was assessed using receiver operating characteristic curves. Among the clinical variables, tumor grade and FIGO stage were independent risk factors, and the areas under the curve (AUCs) of the clinical model were 0.741 and 0.749 in the training and testing groups. The Rad-score, consisting of 4 radiomics features selected from 200 radiomics features, showed good predictive performance with an AUC of 0.819 in the training group and 0.776 in the testing group, which were higher than the clinical model, but the difference was not statistically significant. The combined model constructed with tumor grade, FIGO stage, and Rad-score achieved the best performance, with an AUC of 0.857 in the training group and 0.842 in the testing group, which were significantly higher than the clinical model. MRI-based radiomics features could be used as a noninvasive biomarker to improve the ability to predict the treatment response to CCRT in patients with LACSC.

S3519 A Rare Case of Epigastric Pain Caused by Duodenal Metastatic Cervical Cancer

Introduction: Cervical cancer was previously one of the most common causes of death for women in the United States but survival has since improved with the use of screening and the HPV vaccine. Metastatic cervical cancer spread to the duodenum is rare and presents a diagnostic challenge due to vague symptoms. We present a case of epigastric pain caused by invasive squamous cell cervical cancer with duodenal metastasis. Case Description/Methods: A 59-year-old female with a history of GERD and treated cervical cancer (2 years prior) and currently on pembrolizumab presented to clinic for 3 months of progressive upper abdominal pain and dyspepsia. Last upper endoscopy a year ago was normal. Physical exam was notable for epigastric tenderness without guarding. Laboratory data was remarkable for downtrending hemoglobin, normal liver function tests, normal lipase, and negative stool H pylori antigen. She was referred for EGD. A contrasted CT of the abdomen and pelvis performed revealed multiple enlarged lymph nodes of the mesentery. Upper endoscopy revealed thickened folds of the second portion of the duodenum and multiple biopsies taken of this site. It was an otherwise normal upper endoscopy. The duodenal biopsies were positive for metastatic squamous cancer of the cervix. The patient was transitioned to treatment with gemcitabine and carboplatin due to progressive disease on pembrolizumab. She unfortunately succumbed to her disease six months later. (Figure) Discussion: There is an estimated 7.5 per 100,000 new cases of cervical cancer per year with death rate of 2.2 per 100,000 in the United States. Cervical cancer is usually locally invasive and spreads by lymphatics or hematogenously with most common metastatic sites of lungs, liver, and bone. In a previous review, liver metastases was in up to 12.5% of patients but did not mention a single case of luminal disease. It is very rare for most cancers to metastasize to the gastrointestinal tract, but when present, metastasis has a predilection for the stomach and duodenum. Few case reports are available for cervical cancer metastasis to the GI tract specifically, with about 16 identified. These patients generally presented with gastrointestinal bleeding, bowel perforation, nonspecific abdominal pain or obstructive symptoms. In conclusion, duodenal metastasis of cervical cancer is rare and can be frequently missed. A high degree of suspicion can expedite referral for upper endoscopy to diagnose and allow for treatment to extend patients’ quality of life.Figure 1.: Thickened folds in the second portion of duodenum.

S2882 Uterine Cervical Squamous Cell Carcinoma: A Rare Cause of Biliary Obstruction

Introduction: The incidence of biliary obstruction is 5 cases per 1000 people in the United States with reports of 21% caused by metastatic lesions to the pancreaticobiliary system. Metastatic lesion to the pancreas is rare, with few cases on uterine squamous cell cancer (SCC) metastasizing to the pancreas. We present a case report of a uterine cervical SCC with metastasis to the pancreas resulting in biliary obstruction. Case Description/Methods: A 51-year-old female with a history of stage 4b uterine cervical SCC previously treated with radiation and chemotherapy six years prior presented with elevated aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels two times the upper limit of normal and jaundice. Prior to presentation she was in remission. However, CT on presentation demonstrated new thickening of the midthoracic esophagus, with subcarinal lymphadenopathy and a 1.9 x 2.2 cm mass in the uncinate process of the pancreas causing biliary dilation. Follow-up PET imaging showed evidence of a new intense uptake in the pre-carinal space and new pancreatic head involvement (Figure 1a). She simultaneously underwent an Endoscopic Ultrasound (EUS) and Endoscopic retrograde cholangiopancreatography (ERCP) for stent placement (Figure 1b). EUS showed a 21 mm x 20 mm hypoechoic lesion at the pancreatic head/uncinate process (Figure c). A fine needle biopsy was performed. Pathologic evaluation was consistent with a metastatic lesion secondary to a keratinizing SCC subtype was identified. (Figure d). Discussion: Metastasis to the pancreas accounts for 2-5% of pancreatic malignancies. Majority of SCC are associated with cervical high risk-human papilloma virus (HPV) with HPV-16 and HPV-18 being responsible for the most common types of cervical cancers. To date there have been only two published reports in the literature on SCC of the uterine cervix metastasizing to the pancreas. This case report emphasizes the importance of differentiating primary pancreatic carcinomas from metastatic lesions to the pancreas from other primary sources. There are various imaging modalities for diagnosis such as PET, CT, MRI/MRCP, ultrasonography, and EUS. In our case we were able to identify a new mass in the pancreas with CT, MRI and PET imaging and diagnose it with EUS. The usage of EUS to achieve accurate histopathologic diagnosis is becoming more important to tailor specific management and treatment options for pancreatic tumorsFigure 1.: a: PET avid lesion; b: Stricture as seen on ERCP within the distal CBD; c: Pancreatic mass on EUS; d: pancreatic tissue involved by sheets of cells with round to oval and angulated nuclei, moderate amounts of dense eosinophilic cytoplasm, intercellular bridges, and focal keratin formation. Scattered mitoses, dyskeratotic keratinocytes and apoptotic debris

Dose-effect relationship between dose-volume parameters of residual gross tumor volume and clinical prognosis in MRI-guided adaptive brachytherapy for locally advanced cervical cancer: asingle-center retrospective study.

To investigate the dose-effect relationship between the dose-volume parameters of residual gross tumor volume (GTVres) and clinical prognosis in MRI image-guided adaptive brachytherapy (IGABT) of patients with locally advanced cervical cancer in our center. The clinical data of 93patients with locally advanced cervical squamous cell cancer who received external beam radiotherapy (EBRT) combined with IGABT ± chemotherapy in our center were retrospectively analyzed. The disease stage, overall treatment time (OTT), chemotherapy, and the dose-volume parameters D90, D98, and D100 of GTVres, the intermediate-risk clinical target volume (CTVIR), and the high-risk clinical target volume (CTVHR) of the patients were statistically analyzed. Kaplan-Meier and uni- and multivariable Cox regression analyses were used to analyze 2‑year overall survival (OS), progression-free survival (PFS), and local control rate (LC). Aprobit model was employed to assess the dose-effect relationship between the volume and dose-volume parameters of GTVres and 2‑year OS, PFS, and LC. The median follow-up time was 19.6months and 2‑year OS, PFS, and LC were 79.6%, 68.8%, and 94.6%, respectively. CTVHR D90 was an independent influencing factor for 2‑year PFS (P = 0.041); GTVresBT1 volume was an independent factor for 2‑year OS, PFS, and LC (P < 0.001). The probit model showed that at GTVresBT1 volume < 32.86 cm3, the expected 2‑year LC was > 90%; at GTVres D98 > 129.12 GyEQD2, the expected 2‑year OS was > 90%. Both the volume and dose-volume parameters of GTVres are promising predictors in assessment of IGABT prognosis of cervical cancer.

Pilot Cervical Cancer Navigation Program Outcomes from a Tertiary Tanzanian Academic Institute (037)

Pilot Cervical Cancer Navigation Program Outcomes from a Tertiary Tanzanian Academic Institute (037)

MRI-based radiomics value for predicting the survival of patients with locally advanced cervical squamous cell cancer treated with concurrent chemoradiotherapy

BackgroundTo investigate the magnetic resonance imaging (MRI)-based radiomics value in predicting the survival of patients with locally advanced cervical squamous cell cancer (LACSC) treated with concurrent chemoradiotherapy (CCRT).MethodsA total of 185 patients (training group: n = 128; testing group: n = 57) with LACSC treated with CCRT between January 2014 and December 2018 were retrospectively enrolled in this study. A total of 400 radiomics features were extracted from T2-weighted imaging, apparent diffusion coefficient map, arterial- and delayed-phase contrast-enhanced MRI. Univariate Cox regression and least absolute shrinkage and selection operator Cox regression was applied to select radiomics features and clinical characteristics that could independently predict progression-free survival (PFS) and overall survival (OS). The predictive capability of the prediction model was evaluated using Harrell’s C-index. Nomograms and calibration curves were then generated. Survival curves were generated using the Kaplan-Meier method, and the log-rank test was used for comparison.ResultsThe radiomics score achieved significantly better predictive performance for the estimation of PFS (C-index, 0.764 for training and 0.762 for testing) and OS (C-index, 0.793 for training and 0.750 for testing), compared with the 2018 FIGO staging system (C-index for PFS, 0.657 for training and 0.677 for testing; C-index for OS, 0.665 for training and 0.633 for testing) and clinical-predicting model (C-index for PFS, 0.731 for training and 0.725 for testing; C-index for OS, 0.708 for training and 0.693 for testing) (P < 0.05). The combined model constructed with T stage, lymph node metastasis position, and radiomics score achieved the best performance for the estimation of PFS (C-index, 0.792 for training and 0.809 for testing) and OS (C-index, 0.822 for training and 0.785 for testing), which were significantly higher than those of the radiomics score (P < 0.05).ConclusionsThe MRI-based radiomics score could provide effective information in predicting the PFS and OS in patients with LACSC treated with CCRT. The combined model (including MRI-based radiomics score and clinical characteristics) showed the best prediction performance.

Assessment of Response Rate and Toxicity in Locally Advanced Squamous Cell Carcinoma Cervix with Induction Chemotherapy Followed by Radiotherapy in Comparison with Concurrent Chemoradiation

Objective: To compare the toxicity, response rate, and survival of concurrent chemo radiotherapy and induction chemotherapy followed by radiotherapy alone in squamous cell cervical cancer patients. Place and duration of study: Radiation Oncology Department of Nishtar Hospital for 1 year Study design: A comparative retrospective study Methodology: A total of 60 women were included in the study who have been diagnosed with stage IB2 to stage IIIB squamous cell cervical carcinoma. After passing the inclusion and exclusion criteria, patients were divided into two groups, a concurrent chemo radiotherapy group (30 patients) and a radiotherapy group (30 patients) by consecutive data sampling. All the patients were subject to external beam radiotherapy to the 45 Gy to whole pelvis with 15 MV X-rays 5 days/week by using the four-field technique. The patients in the radiotherapy group were given induction chemotherapy with cisplatin 50 mg/m2 every 21 days with paclitexal 175mg/m2 (2 cycles) followed by radiotherapy alone. For the patients of concurrent chemo radiotherapy, patients were administered 40 mg/m2 cisplatin weekly with radiations for 5 cycles. Results: The overall response rate for CCRT group and RT group was 65% (n=30) and 50% (n=30) respectively. The overall survival rate was 12 months and 8 months for the CCRT group and RT group respectively. Similarly, relapse-free survival was 10 months in CCRT patients and 6 months in RT patients. The rate of hematological toxicities was more in CCRT patients. The most common adverse effect was diarrhea with 3 (10%) patients in the CCRT and 2 (6.6%) patients in the RT group. No deaths occurred due to treatment. Conclusion: The efficacy and toxicity of CCRT show promising results in squamous cell cervical carcinoma patients as compared to induction chemotherapy followed by radiotherapy treatment alone. Keywords: Concurrent chemoradiotherapy. Radiotherapy, squamous cell cervical carcinoma, toxicity

Down-regulated expression of miR-99a is associated with lymph node metastasis and predicts poor outcome in stage IB cervical squamous cell carcinoma: a case-control study.

Background Lymph node metastasis (LNM) accounts for the most important route of metastasis for cervical cancer. Yet, the status of LNM is different in patients with similar clinico-pathological variables. It has been revealed that microRNAs are widely involved in the occurrence and development of various malignancies, and the tumor-suppressive or promoting effects of microRNA-99 (miR-99) family have been previously reported. This study sought to investigate the predictive value of miR-99a for lymphogenous spread and its effect on the survival of patients with early-stage cervical squamous cell cancer (CSCC).MethodsPatients with stage IB squamous cervical cancer who were treated surgically between October 2015 and November 2018 were enrolled. A total of 21 formalin-fixed paraffin-embedded tissues of pathologically confirmed positive lymph nodes were retrieved, and an additional 21 tissues of negative lymph nodes from patients well-matched on baseline characteristics were collected as the control group. TaqMan real-time quantitative polymerase chain reaction was used to examine the expression levels of miR-99a in the samples. Differential expression levels of miR-99a were compared between the 2 groups using independent sample t-test. Furthermore, the associations between miR-99a expression level and clinico-pathological parameters of these 42 patients was evaluated by Chi-square test or Fisher’s exact-probability method, and their effects on survival were assessed using Kaplan-Meier product-limit method.ResultsThere were no significant differences in baseline clinico-pathological parameters between the 2 groups (P>0.05). The expression levels of miR-99a in the node-positive group and control group were 1.61±3.09 and 16.77±30.40, respectively (P=0.029). Downregulated expression of miR-99a was closely related to depth of invasion (DOI) and lymph-vascular space invasion (P<0.05). Univariate analysis revealed that downregulated miR-99a and deeper DOI were associated with worse 5-year disease-free survival, while multivariate analysis showed that only the expression level of miR-99a was an independent factor for disease-free survival (HR =0.120; 95% CI: 0.015–0.979; P=0.048). Patients with downregulated miR-99a tended to have more unfavorable overall survival, but the difference did not reach statistical significance.Conclusions MiR-99a plays an inhibitory role in the pathogenesis of lymph node metastasis and may serve as a novel prognostic biomarker for patients with CSCC.

HNF1A-AS1: A Tumor-associated Long Non-coding RNA.

Hepatocyte nuclear factor 1 homeobox A antisense RNA 1 (HNF1A-AS1) is a Long non-coding RNA (LncRNA) that participates in the occurrence and development of lots of tumors and is supposed to be a new biomarker. The text aims to illustrate the biological effect, specific mechanism and clinical significance of HNF1A-AS1 in various tumors. Via consulting the literature, analyze and summarize the relationship between HNF1A-AS1 and all kinds of tumors and the specific mechanism. This is a review paper about the tumor-associated long non-coding RNA HNF1A-AS1. Many researches show that LncRNA HNF1A-AS1 is related to the development of tumorous tumors. Its expression is up-regulated in numerous tumors, such as oral squamous cell carcinoma, hepatocellular carcinoma, breast cancer, osteosarcoma, lung cancer, cervical cancer, bladder cancer, colon cancer, colorectal cancer, oesophageal adenocarcinoma and laryngeal squamous cell carcinoma. However, HNF1A-AS1 is down-regulated in gastroenteropancreatic, neuroendocrine neoplasms, oral squamous cell carcinoma. Furthermore, HNF1A-AS1 can affect tumor proliferation, invasion, migration and apoptosis by targeting some microRNAs-miR-661 and miR-124. HNF1A-AS1 can also influence the development of tumors by regulating EMT. These studies show that LncRNA-HNF1A-AS1 is closely related to the occurrence development of numerous cancers. Through various molecular mechanisms to regulate tumor growth, HNF1A-AS1 can possibly become the new biological biomarker and therapeutic target for many kinds of tumors.

The Value of Whole-Tumor Texture Analysis of ADC in Predicting the Early Recurrence of Locally Advanced Cervical Squamous Cell Cancer Treated With Concurrent Chemoradiotherapy.

ObjectivesTo investigate the value of whole-tumor texture analysis of apparent diffusion coefficient (ADC) map in predicting the early recurrence of patients with locally advanced cervical squamous cell cancer (LACSC) treated with concurrent chemoradiotherapy (CCRT) and establish a combined prediction model including clinical variables and first-order texture features.MethodsIn total, 219 patients (training: n = 153; testing: n = 66) with stage IIB-IVA LACSC treated by CCRT between January 2014 and December 2019 were retrospectively enrolled in this study. Clinical variables and 22 first-order texture features extracted from ADC map were collected. The Mann-Whitney U test or independent sample t test, chi-square test or Fisher’s exact were used to analyze statistically significant parameters, logistic regression analysis was used for multivariate analysis, and receiver operating characteristic analysis was used to compare the diagnostic performance.ResultsIn the clinical variables, T stage and lymph node metastasis (LNM) were independent risk factors, and the areas under the curve (AUCs) of the clinical model were 0.697 and 0.667 in the training and testing cohorts, the sensitivity and specificity were 48.8% and 85.5% in the training cohort, and 84.1% and 51.1% in the testing cohort, respectively. In the first-order texture features, mean absolute deviation (MAD) was the independent protective factor, with an AUC of 0.756 in the training cohort and 0.783 in the testing cohort. The sensitivity and specificity were 95.3% and 52.7% in the training cohort and 94.7% and 53.2% in the testing cohort, respectively. The combined model (MAD, T stage, and LNM) was established, it exhibited the highest AUC of 0.804 in the training cohort and 0.821 in the testing cohort, which was significantly higher than the AUC of the clinical prediction model. The sensitivity and specificity were 67.4% and 85.5% in the training cohort and 94.7% and 70.2% in the testing cohort, respectively.ConclusionsThe first-order texture features of the ADC map could be used along with clinical predictive biomarkers to predict early recurrence in patients with LACSC treated by CCRT.

Added-value of texture analysis of ADC in predicting the survival of patients with 2018 FIGO stage IIICr cervical cancer treated by concurrent chemoradiotherapy

PurposeTo investigate the value of texture analysis of ADC in predicting the survival of patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIICr cervical squamous cell cancer (CSCC) treated with concurrent chemoradiotherapy (CCRT). MethodsA total of 91 patients with stage IIICr CSCC treated by CCRT between January 2014 and December 2018 were retrospectivelyenrolled in this study. Clinical variables and 21 first-order texture features extracted from ADC maps were collected. Univariate and multivariate Cox hazard regression analyses were performed to evaluate these parameters in predicting progression-free survival (PFS) and overall survival (OS). The independent variables were combined to build a prediction model and compared with the 2018 FIGO staging system. Survival curves were generated using the Kaplan-Meier method, and the log-rank test was used for comparison. ResultsMean Absolute Deviation (MAD), T stage, and the number of lymph node metastasis (LNM) were independently associated with PFS, while MAD, energy, T stage, number of LNM, and tumor grade were independently associated with OS. The C-index values of the combined models for PFS and OS, which were respectively 0.750 and 0.832, were significantly higher compared to 2018 FIGO staging system values of 0.629 and 0.630, respectively (P < 0.05). ConclusionsThe texture analysis of the ADC maps could be used along with clinical prognostic biomarkers to predict PFS and OS in patients with stage IIICr CSCC treated by CCRT.