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Takotsubo cardiomyopathy (TCM) secondary to an infusion reaction is extremely rare in the literature. Here, we present an unusual case of TCM in a patient with cervical squamous cell carcinoma who presented with acute hypoxic respiratory failure following the initiation of the first-cycle paclitaxel infusion therapy.

Effect of bone marrow mesenchymal stem cells (BMSCs) on the sensitivity of chemotherapy drugs and microRNAs (miRNAs) is still unclear. This study explored the role of miR-140 modified BMSCs in enhancing paclitaxel sensitivity of cervical squamous cell carcinoma (CSCC). Hela cells, BMSCs cells, and miR-140 modified BMSCs were transfected with miR-140 mimic, miR-140 inhibitor, and miR-140 NC, respectively. After transfection, they were co-cultured with Hela cells and paclitaxel to set up miR-140 mimic group, miR-140 inhibitor group, and miR-140 NC group (without paclitaxel treatment) followed by analysis of cell proliferation, apoptosis, ROS generation, expression of miR-140, STMN1, STAT3, p-STAT3, and survivin mRNA and protein. miR-140 inhibitor group showed lowest cell proliferation number and expressions of miR-140, STMN1, STAT3, p-STAT3, and survivin mRNA and protein with highest number of apoptotic cells, which were all reversed in miR-140 mimic group. There was a positive correlation between STMN1 level and miR-140 expression (r = 0.449, P = 0.108). BMSCs modified with miR-140 inhibitor can target STMN1, enhance the sensitivity of chemotherapy drugs, and exert an inhibitory effect on CSCC cell proliferation, suggesting that STMN1 might be a therapy target for treating CSCC.

Aim: To investigate the effect of rs3733846 in the flanking region of miR-143/145 on susceptibility to cervical squamous cell carcinoma (CSCC). Materials & methods: We collected venous blood samples from 242 CSCC patients and 250 healthy controls. The rs3733846 polymorphism was genotyped by SnaPshot and Sanger sequencing. The expression of miR-143/145 in CSCC tissues was detected by quantitative real-time PCR. Results: The rs3733846 AG genotype was associated with a decreased risk of CSCC in genetic model (AGvs.AA: adjusted odds ratio [OR]: 0.44; 95% CI: 0.30–0.66; p < 0.001). Patients with the rs3733846 AG/GG genotypes had a reduced risk of developing poorly differential status (OR: 0.57; 95% CI: 0.33–0.98; p < 0.04) and lymph node metastasis (OR: 0.49; 95% CI: 0.26–0.92; p < 0.03). Conclusion: The rs3733846 in the flanking region of miR-143/145 was related to the susceptibility of CSCC.

BACKGROUND Extramedullary plasmacytoma (EMP), a variant form of myeloma, is a rare solid plasma cell tumor that originates from the bone marrow hematopoietic tissue and accounts for about 3% of all plasma cell tumors. EMP can affect various tissues and organs, about 90% of which is found in the head and neck. However, EMP in the reproductive organs is rare, and is difficult to be distinguished from other primary or metastatic genital tumors according to clinical symptoms and imaging findings. CASE SUMMARY Herein, we report a case with coexistence of EMP and squamous cell carcinoma in the cervix. The first histopathological report of neoplasms on the surface of the cervix and vagina showed an EMP. Both ultrasound and pelvic enhanced magnetic resonance imaging (MRI) indicated that there was a tumor in the cervix. Thus, another cervical biopsy and pathological examination were performed, which indicated EMP combined with squamous cell carcinoma. Then, the patient underwent extensive total hysterectomy (type C1) + systemic lymph node dissection and received 25 external pelvic irradiations with a dose of 50 Gy following surgery. During 2-year follow-up, no recurrence was reported. CONCLUSION In conclusion, EMP involving the reproductive system is relatively rare. In this case, MRI, B-ultrasound, and cervical canal scraping were used to further determine the diagnosis of EMP combined with squamous cell carcinoma. The patient had improved prognosis after appropriate treatments.

AIM We aimed to screen for the genes related to survival prognosis of cervical squamous cell carcinoma (CSCC) and then constructed a prognosis prediction model. METHODS The GSE63514 dataset was obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). The CSCC gene dataset and the GSE44001 dataset were obtained from The Cancer Genome Atlas and NCBI GEO, respectively. The Kaplan-Meier (KM) curve was used to evaluate the association between high and low prognosis that was with the actual survival prognosis information. The Cox proportional hazards model was used to screen out the optimized prognostic-related signature differentially expressed gene (DEG) combinations. Gene set enrichment analysis was used to perform pathway enrichment annotation analysis for DEGs that were related to risk grouping. RESULTS In total, 16 399 DEGs were obtained and 23 gene ontology biological processes and 8 Kyoto Encyclopedia of Genes and Genomes pathways were screened. Nine optimized DEG groups related to independent prognosis were selected. The KM curves of pathologic N0 and N1 showed that low-risk group were associated with a better overall survival (p = 1.518e; p = 1.704e-01). The pathways related to risk grouping were cytokine-cytokine receptor interaction, JAK stat signaling pathway, and glycolysis-gluconeogenesis. CONCLUSION On the basis of this study, we established a prognostic risk model, which provided a reliable prognostic tool and was of great significance for locating the biomarkers related to survival prognosis in CSCC.

Objective This study aimed to evaluate the clinical outcomes for patients with stage IB2/IIA2 cervical squamous cell carcinoma treated with neoadjuvant chemotherapy combined with radical surgery. Methods A total of 68 patients with cervical squamous cell carcinoma were randomly divided into the experimental group (n = 35) and the control group (n = 33). The patients in the experimental group received paclitaxel plus cisplatin neoadjuvant chemotherapy for two cycles, then underwent radical hysterectomy and bilateral adnexectomy at 2 weeks post-chemotherapy. The control group only underwent radical hysterectomy and bilateral adnexectomy after the diagnosis of cervical squamous cell carcinoma. The toxic and side effects of chemotherapy in the experimental group were observed. Also, the operation method, operation time, blood loss, grade of wound healing, complications, and postoperative pathology were noted in the two groups. Primary foci and pelvic lymph node recurrence and distant metastasis were observed, and 3-year and 5-year survival rates were calculated. Results Only one patient in the experiment had grade III bone marrow suppression; no other grade III and IV chemotherapy toxic reactions were observed. The operation was successfully completed in all patients. The operation time, intraoperative blood loss, placement of the ureteral catheter, bladder injury, ureteric injury, postoperative urinary tub, pelvic drainage tube indwelling time, anal exhaust time, postoperative complications, and metastatic ratio of lymph nodes were not significantly different between the two groups (P > 0.05). The number of dissected lymph nodes, deep myometrial invasion, and vascular tumor emboli showed a significant difference in the experimental group compared with the control group (P < 0.05). The 3-year disease-free survival (82.9% vs 81.9%), 5-year disease-free survival (71.4% vs 60.6%), 3-year overall survival (91.4% vs 87.8%), and 5-year overall survival (82.9% vs 75.6%) were not statistically significantly different between the experimental group and the control group (P > 0.05). Conclusions Neoadjuvant chemotherapy in IB2/IIA2 stage cervical squamous cell carcinoma showed low toxic side effects. Radical surgery after chemotherapy is safe and feasible. It plays a coordinating role in reducing the tumor infiltration depth of the deep muscle layer and the incidence of vascular tumor emboli, reducing the use of postoperative adjuvant therapy, and improving the quality of life of patients, but does not improve the 3-year/5-year survival rate.

Objective To evaluate the efficacy and superiority of loop electrosurgical excision procedure (LEEP) in managing stage IA1 cervical microinvasive squamous cell carcinoma (MISCC) without lymph-vascular space invasion (LVSI). Materials and methods The oncological and reproductive outcomes of a series of patients affected by stage IA1 MISCC without LVSI, initially treated by LEEP between February 2006 and December 2017, were retrospectively reviewed. Results Ultimately, 109 patients were included. The mean age at diagnosis was 35.4 years old, and 36 patients were nulliparous. Multifocal lesions were identified in 15 patients (13.8%). The mean cone depth was 17.4 mm. Resection margins were positive/unevaluable and negative in 26 (23.9%) and 83 (76.1%) cases, respectively. Among cases undergoing salvage treatments, the residual disease rate for patients with positive/unevaluable margins was significantly higher than those with negative margins (P = 0.003). During the follow-up period of 43.0 ± 28.9 months, no relapse was identified. Fifteen of 20 patients (75.0%) conceived successfully, with a full-term live birth rate of 93.3%. Conclusions For stage IA1 MISCC without LVSI unexpectedly found in a loop excision, initial LEEP with clear margin is efficient and adequate. For cases with multifocal MISCC, or for those young patients who wish to become pregnant in the future, LEEP is the optimal choice.

Objective. We aimed to demonstrate whether the immunohistochemical expression of C-erb-B2 and progesterone receptors are valuable in the diagnosis of intraepithelial cervical neoplasia and squamous cell carcinoma. Methods and Results. Our retrospective study, a total of 84 cases diagnosed as squamous cell carcinoma and cervical intraepithelial neoplasia during 2005-2009, at the pathology department of Harran University, was investigated and stained with immunohistochemistry. Progesterone receptor was stained positive in 5 of 21 cervical intraepithelial neoplasia I. As a result of the statistical analysis (SPSS statistic 15.0), a significant correlation was found for positive progesterone receptors. No positive staining was seen in any of the cases with CerbB2 (p>0,05). Conclusions. In this study, it was concluded that positive progesterone receptors can be used to distinguish cases of cervical intraepithelial neoplasia I from other dysplasia and carcinoma, while Cerb-B2 has not been shown to be useful in distinguishing between these lesions.

OBJECTIVE To compare long-term outcomes between pre-operative radiotherapy followed by open surgery and direct open surgery among women with Stage IB1-IIB cervical squamous cell carcinoma. METHODS A multicenter retrospective cohort study among women with Stage IB1-IIB cervical squamous cell carcinoma who underwent open surgery either directly (SD group) or with pre-operative radiotherapy (PR group) in China 2004-2016. Five-year overall survival (OS) and disease-free survival (DFS) between the two groups were compared by Kaplan-Meier methods and multivariate Cox regression. RESULTS Overall, 8385 women with Stage IB1-IIB were included (PR group, n = 447; SD group, n = 7938). Five-year OS and DFS was significantly lower in the PR than in the SD group (OS: 81.7% vs 91.6%, P

Lymph node metastasis (LNM), a critical prognostic determinant in cancer patients, is critically influenced by the presence of numerous heterogeneous cancer-associated fibroblasts (CAFs) in the tumor microenvironment. However, the phenotypes and characteristics of the various pro-metastatic CAF subsets in cervical squamous cell carcinoma (CSCC) remain unknown. Here, we describe a CAF subpopulation with elevated periostin expression (periostin+ CAFs), located in the primary tumor sites and metastatic lymph nodes, that positively correlated with LNM and poor survival in CSCC patients. Mechanistically, periostin+ CAFs impaired lymphatic endothelial barriers by activating the integrin-FAK/Src-VE-cadherin signaling pathway in lymphatic endothelial cells and consequently enhanced metastatic dissemination. In contrast, inhibition of the FAK/Src signaling pathway alleviated periostin-induced lymphatic endothelial barrier dysfunction and its related effects. Notably, periostin- CAFs were incapable of impairing endothelial barrier integrity, which may explain the occurrence of CAF-enriched cases without LNM. In conclusion, we identified a specific periostin+ CAF subset that promotes LNM in CSCC, mainly by impairing the lymphatic endothelial barriers, thus providing the basis for potential stromal fibroblast-targeted interventions that block CAF-dependent metastasis.

OBJECTIVE: In this study, we determined the prognostic values of magnetic resonance imaging (MRI)-based primary tumor regression and serum squamous cell carcinoma antigen (SSCC-Ag) levels 4 weeks after definitive radiotherapy (RT) in cervical squamous cell carcinoma (CSCC) patients. METHODS: This was a retrospective study involving 218 patients with histologically confirmed CSCC (stages IB-IVA). All the patients received definitive RT. Pre- and post-RT pelvic MRI and SSCC-Ag levels were measured. Locoregional control (LRC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated, and possible OS prognostic factors were analyzed. RESULTS: The median follow-up time was 25.57 (1.73–58.93) months. Thirty-six and 68 patients died and experienced recurrence, respectively, and the primary tumors of 130 (59.6%) and 88 (40.4%) patients exhibited complete response (CR) and non-CR, respectively. The 3-year OS, DFS, LRC, and DMFS rates were significantly higher in the CR than in the non-CR patients (85.2% vs. 67.9%, 78.9% vs. 39.0%, 93.4% vs. 63.8%, and 83.4% vs. 54.5%, respectively; p< 0.05). The 3-year OS, DFS, LRC, and DMFS rates were significantly lower in the patients with high post-RT SSCC-Ag levels than in those with low post-RT SSCC-Ag levels (38.0% vs. 83.9%, 21.2% vs. 66.3%, 73.0% vs. 84.9%, and 26.5% vs. 79.0%, respectively; p

The mortality caused by cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) ranks second among female malignant tumour deaths, but their diagnostic and therapeutic targets are still limited. N6-methyladenosine (m6A) is the most common and extensive modification in mRNA molecules, and its methylation regulators participate in regulating the occurrence and development of many tumours. However, whether m6A RNA methylation regulators can be used as independent prognostic indicators of CESC remains unknown. This study unveiled differential expression of 20 m6A RNA methylation regulators between normal and CESC tumour samples, which RNA sequence data and clinical information were obtained from TCGA database. As a result, five m6A RNA methylation regulators (FTO, HNRNPA2B1, RBM15, IGF2BP1, IGF2BP3) were identified to be significantly linked to CESC tumour status. After Lasso cox regression analysis, six m6A RNA methylation regulators (YTHDC2, YTHDC1, ALKBH5, ZC3H13, RBMX, YTHDF1) were chosen to construct a risk signature. CESC patients were then classified as high-risk and low-risk group based on the median risk score. The overall survival (OS) of the CESC patients in high-risk group was significantly lower than that in low-risk group, and the area under curve (AUC) is 0.718. Moreover, the risk model can be an independent prognosis factors for CESC patients and can predict OS of CESC patients with different clinical factors. In conclusion, m6A RNA methylation regulators are closely correlated with CESC clinical characteristics and the selected six m6A RNA methylation regulators may be useful for CESC patients personalized treatment.

Background and objective: P63 is a member of the p53 gene family. It plays an essential role in the normal development of the cervix. This study aimed to assess p63 expression in different cervical lesions and the correlation between their expression in cervical intraepithelial neoplastic changes and invasive cervical cancer. Methods: A total of 62 cervical tissues were performed for p63 immunostaining, including 15 samples of non-neoplastic reactive cervicitis, 27 cervical intraepithelial neoplastic changes, and 15 invasive cervical cancer cases as well as five samples of normal cervical tissue as control. Results: P63 in normal cervical squamous epithelium had restricted staining pattern in the nuclei of basal cells. Reactive cervicitis staining ranged from restricted staining pattern in basal cells to mild increase in staining intensity involving upper parabasal cells. P63 was positive in all CIN lesions, and staining intensity increased significantly with increasing severity of cervical intraepithelial lesions compared with non-neoplastic epithelium. All cervical squamous cell carcinoma had high staining intensity while adenocarcinoma and small cell carcinoma were stained negative. Conclusion: P63 can be used as a marker for the distinction between reactive cervicitis and cervical intraepithelial changes. It is also of value for grading of CIN lesions and differentiation between squamous cell carcinoma, adenocarcinoma, and small cell carcinoma.

Background This study aimed to investigate the correlation between the level of HPV16 and HPV18 in patients with cervical lesions and the local vaginal immunity after receiving treatment with different degrees of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC). Methods One hundred and thirty-six patients with LSIL (grade 1 CIN or CIN 1), 263 patients with HSIL (grade 2 and 3 CIN or CIN 2 and 3), and 33 patients with CSCC pathologically confirmed between November 2012 and September 2016 were assigned to the test group and 100 healthy women in the same period were assigned to the control group. ELISA was used to determine the levels of SIgA, IgG, IL-2, and IL-10 and the IL-2/IL-10 ratio in vaginal lavage fluid in the test group (before treatment and 3, 6, and 12 months after treatment) and the control group, respectively. Gene chip technology was adopted to test the HPV infection in the test group (before treatment and 3, 6, and 12 months after treatment) and the control group, respectively. Results The results showed that the levels of SIgA, IgG, and IL-10 were positively correlated with the degree of cervical lesions and IL-2/IL-10 was negatively correlated with the degree in all patients before treatment. The levels of SIgA, IgG, and IL-10 were positively correlated with the degree of cervical lesions and IL-2/IL-10 was negatively correlated with the degree in HPV16 and HPV18-infected patients before receiving the treatment. Conclusions The recovery after the treatment of HPV infection is time-dependent and the immune system of patients with CIN starts to recover in the 6th month after treatment, early intervention is not recommended. However, the immune system is approximately in a normal sate at 12 months after treatment, at which time the efficacy can be evaluated, and clinical intervention can be initiated if necessary. The level of local immune factors in the vagina can be monitored to determine the progression and prognosis of patients’ cervical lesions.

BACKGROUND: Cervical cancer is one of the most prevalent cancers in women. Even with similar clinicopathologic features, radiotherapy outcomes are still vary among patients. This research was conducted to measure radiotherapy responses on cervical cancer patients by using Survivin, Telomerase and Cytochrome C.METHODS: Subjects who matched the criteria were selected and requested to fill questionnaires. Subjects were then evaluated with magnetic resonance imaging (MRI) pre- and post-3D conformal radiotherapy. Histopathological study was conducted using resected tumors to determine the differentiation type. Enzyme-linked Immunosorbent Assays for detection of Survivin, Telomerase and Cytochrome C was performed using the resected tumors as well.RESULTS: There were 76 patients in this study. Mean ofage was 50 and diameter of tumor size was 5.35 cm. Mean levels of Survivin, Telomerase and Cytochrome C were 632.82 pg/mL, 5.59 pg/mL and 204.75 ng/mL, respectively. There were significant correlations between radiotherapy response and Survivin (p=0.041) or Telomerase (p=0.022). Subjects with lower Survivin level (

Background To explore the independent risk factors of cervical squamous cell carcinoma and establish a Nomogram model to predict the prognosis of patients. Methods We randomly divided the total data of patients with cervical squamous cell carcinoma from 2010 to 2015 obtained from the SEER database and cleaned them into training and verification cohorts. The Cox proportional hazard regression model was used to perform univariate and multivariate analyses on the three cohorts of data including the total data. After the intersection, the independent factors and their nomograms with statistical significance were obtained, and the degree of differentiation and calibration between predicted results and real values were obtained by using C-index and calibration map respectively. In addition, the ROC curve was used for correction and evaluation, and the 1-, 3- and 5-year overall and specific survival rates of patients were finally predicted. Results We found age, surgical condition of the primary site and tumor size were all independent factors of cervical cancer. The high-risk survival rates of patients at 1, 3 and 5 years were 77.7%, 48.6% and 36.4%, respectively. We determined that minimally invasive hysterectomy and uterine-preserving surgery (UPS) have a better survival rate for early (stage I) tumors or tumor diameter less than 20 mm. For the late (stage III–IV) or tumor diameter greater than 20 mm, auxiliary open hysterectomy after radiotherapy, and requires careful evaluation of the postoperative residual tumor is the best policy. Conclusions The constructed nomograms could predict overall survival with good performance, and guide surgical resection in cervical squamous cell carcinoma.

Objective The aim of the present work was to evaluate the folate-receptor 1 (FOLR1) expression in cervical squamous cell carcinoma and its clinical significance. Methods FOLR1 mRNA expression level was detected in the cancer genome atlas (TCGA) database for multiple carcinomas. The FOLR1 mRNA relative expression between tumor tissue and normal cervix tissue of the cervical squamous cell cancer patients was compared by the online data analysis tool of GEPIA. The overall survival (OS) and progression free survival (PFS) between the FOLR1 high and low expression groups were compared by the log-rank test. Thirty one cervical squamous cancer patients and 20 healthy controls were included in and tested for serum FOLR1 protein level detection. Eighty one cervical squamous cell cancer patients who received surgery were included for FOLR1 protein expression detected by immunohistochemistry assay (IHC). The correlation between FOLR1 protein expression and patients’ clinical features was analyzed. Results FOLR1 mRNA was up-regulated in tumor tissue compared to corresponding normal cervical tissue of cervical squamous cell carcinoma. Top 20 genes interacted with FOLR1 was identified through the network with the edges of 146. UBXN10 (r=0.668, P Conclusion: FOLR1 was up-regulated in both serum and cancer tissue of cervical squamous cell carcinoma which may act as diagnostic and prognostic maker for cervical squamous cell cancer.

miR-17-92 cluster was differentially expressed in cervical cancer, playing an important role in regulating cell proliferation, apoptosis, migration, and invasion. The purpose of this study was to investigate the association between polymorphisms (i.e., rs9588884, rs982873, and rs1813389) in the promoter of miR-17-92 and the risk of cervical squamous cell carcinoma (CSCC). The rs9588884 polymorphism was genotyped using a Taqman assay and the rs982873 and rs1813389 polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. The expression levels of miR-17-92 were determined using a quantitative PCR analysis. The rs9588884 GG genotype was associated with a reduced risk of CSCC in homozygote comparison (adjusted OR = 0.47, 95% CI, 0.30-0.75, P = 0.001), dominant model (adjusted OR = 0.67, 95% CI, 0.50-0.91, P = 0.01), and recessive model (adjusted OR = 0.57, 95% CI, 0.38-0.85, P = 0.01). The rs9588884 G allele was also associated with a reduced risk of CSCC in allele comparison (adjusted OR = 0.71, 95% CI, 0.58-0.88, P = 0.002). Moreover, patients with the rs9588884 GG genotype had lower levels of miR-20a compared with the rs9588884 CC genotype (P = 0.03). These findings indicate that the rs9588884 GG genotype was associated with lower levels of miR-20a and eventually related to the risk of CSCC in Chinese women.

Papillary squamotransitional cell carcinoma [PSTCC] is a lesser-known histological subtype of the most common type of cervical squamous cell carcinoma. Papillary carcinomas of the uterine cervix with transitional or squamous differentiation often resembles transitional cell carcinomas of uterine tract. In the literature, PSTCC is underdiagnosed, has late presentation, is more common in post-menopausal age group and has late recurrences. Here we present a case of PSTCC in 40 years female due to its rare occurrence.

Cervical squamous cell carcinoma (CESC) is one of the most common causes of women cancer deaths in worldwide. At present, immunotherapy using immune checkpoint blockade (ICB) has improved the prognosis of many cancer patients and neoantigens generated by mutations may serve as potential biomarkers for ICB therapy. In this study, we observed the missense mutations were the most frequent in the landscapes of gene mutation of CESC samples. The higher level of tumor mutation burden (TMB)patients had higher overall survival (OS). And, there was significantly correlated between high TMB group and high fractions of most immune cells. Univariate and multivariate Cox regression analysis determined five hub genes (IFNG, SERPINA3, CCL4L2, TNFSF15, and IL1R1) to build a prognostic model. In the prognostic model, the low-risk group had a better OS. Also, mutations of the five hub genes mainly affect the infiltration level of D8+ T cells and DCs. These results indicated the model might be used to differentiate patients who have a different response to immunotherapy, which makes individualized therapy possible. In conclusion, our study is valuable for exploring the role of TMB related to immune infiltration in CESC. Moreover, the prognosis model may help predict the sensitivity of patients to immunotherapy and provide underlying biomarkers for personalized immunotherapy.

Highlights • Cervical squamous cell carcinoma does metastasize to the breast. • Vagina exam is essential in a patient who presents with a breast mass. • Immunohistochemistry is key in differentiating a primary lesion from a metastasis.

Cervical squamous cell carcinoma (CSCC) is the major pathological type of cervical cancer (CC), the second most prevalent reproductive system malignant tumor threatening the health of women worldwide. The prognosis of CSCC patients is largely affected by the tumor immune microenvironment (TIME); however, the biomarker landscape related to the immune microenvironment of CSCC and patient prognosis is less characterized. Here, we analyzed RNA-seq data of CSCC patients from The Cancer Genome Atlas (TCGA) database by dividing it into high- and low-immune infiltration groups with the MCP-counter and ESTIMATE R packages. After combining weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis, we found that PLA2G2D, a metabolism-associated gene, is the top gene positively associated with immune infiltration and patient survival. This finding was validated using data from The Cancer Genome Characterization Initiative (CGCI) database and further confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, multiplex immunohistochemistry (mIHC) was performed to confirm the differential infiltration of immune cells between PLA2G2D-high and PLA2G2D-low tumors at the protein level. Our results demonstrated that PLA2G2D expression was significantly correlated with the infiltration of immune cells, especially T cells and macrophages. More importantly, PLA2G2D-high tumors also exhibited higher infiltration of CD8+ T cells inside the tumor region than PLA2G2D-low tumors. In addition, PLA2G2D expression was found to be positively correlated with the expression of multiple immune checkpoint genes (ICPs). Moreover, based on other immunotherapy cohort data, PLA2G2D high expression is correlated with increased cytotoxicity and favorable response to immune checkpoint blockade (ICB) therapy. Hence, PLA2G2D could be a novel potential biomarker for immune cell infiltration, patient survival, and the response to ICB therapy in CSCC and may represent a promising target for the treatment of CSCC patients.

Background Lymphovascular 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. Methods One 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. Results The 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 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 Conclusion The 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 registration This is a retrospective study and there is no experimental intervention on human participants. The Ethics Committee has confirmed that retrospectively registered is not required.

Ren-Liang Li,1 Jiao-Hong Wu,1 Min Guo,1 Li-Xiao Sha,1 Shu-Qi Xia,1 Lian Xu2 1Department of Obstetrics and Gynecology, Wenzhou People’s Hospital, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Lian Xu Tel/Fax +86-57788306071Email lian_xu@163.comPurpose: Genetic variant has been demonstrated to be a risk factor for the occurrence and outcome of cervical squamous cell carcinoma (CSCC). From previous genome wide association studies, 6p21.32 has been identified as a susceptibility locus of CSCC. The purpose of this study was to investigate the association of a polymorphism rs2072915 located in 6p21.32 with the risk of CSCC and examine the potential mechanism of the rs2072915 in CSCC pathogenesis.Patients and Methods: The rs2072915 was genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism. miR-637 and RXRB mRNA expression levels in CSCC patients were examined using quantitative PCR. miR-637 target site was determined using the dual-luciferase reporter assay.Results: The rs2072915 was associated with a significantly increased risk (AA vs TT: adjusted OR = 2.48, 95% CI, 1.57– 3.94, P < 0.001; AT/AA vs TT: adjusted OR = 1.38, 95% CI, 1.06– 1.80, P = 0.018; A vs T: adjusted OR = 1.49, 95% CI, 1.21– 1.84, P < 0.001, respectively) and shorter survival time of CSCC (P = 0.03). Patients with the rs2072915 AA genotype displayed lower levels of RXRB that is a target of miR-637.Conclusion: These findings suggest that the rs2072915 T > A change might augment the binding energy of miR-637 to RXRB, result in lower levels of RXRB, and thus contribute to the risk of CSCC.Keywords: miR-637, polymorphism, survival, cervical squamous cell carcinoma

Background:The expression and biological roles of a novel lncRNA HOXC-AS3 in cervical squamous cell carcinoma (CESC) are largely unknown.Methods:LncRNA HOXC-AS3 was identified from The Cancer Genome Atlas (TCGA) database. Real time quantitative PCR (qRT-PCR) was used to evaluate the expression of HOXC-AS3 in 68 pairs of CESC tumor tissues and adjacent normal tissues. Kaplan-Meier survival analysis was used to assess the significance of HOXC-AS3 in predicting overall survival (OS). Correlations between HOXC-AS3 expression and clinicopathological parameters were assessed using Chi-square test. The biological functions of HOXC-AS3 in CESC were investigated using loss-of and gain-of function assays, which including cell proliferation, migration and invasion. Furthermore, the underlying mechanism was revealed using bioinformatics prediction, qRT-PCR and western blot.Results:HOXC-AS3 expression was significantly up-regulated in CESC tumor tissues. Up-regulated HOXC-AS3 expression was correlated with advanced stage and poor OS. Over-expression of HOXC-AS3 promoted tumor cell proliferation, migration and invasion. Conversely, HOXC-AS3 knockdown significantly inhibited these effects. Subcellular fractionation analysis revealed that HOXC-AS3 was mainly localized in cell nuclei. Further mechanistic analyses demonstrated that HOXC-AS3 down-regulated the expression of FBXL17. The promotive effects of HOXC-AS3 on cell proliferation, migration and invasion could be repressed by FBXL17. Moreover, HOXC-AS3 activated the EMT process to promote the progression of CESC. Conclusion:In conclusion, our study indicated that HOXC-AS3 acted as an oncogenic lncRNA in CESC through downregulating FBXL17 expression and activating EMT process.

Radiotherapy is one of the standard treatments for cervical cancer and head and neck cancer. However, the clinical efficacy of this treatment is limited by radioresistance. The discovery of effective prognostic biomarkers and the identification of new therapeutic targets have helped to overcome the problem of radioresistance. In this study, we show that in the context of PIK3CA mutation or amplification, high expression of fascin actin-bundling protein 1 (FSCN1) (using the median as the cut-off value) is associated with poor prognosis and radiotherapy response in cancer patients. Silencing FSCN1 enhances radiosensitivity and promotes apoptosis in cancer cells with PIK3CA alterations, and this process may be associated with the downregulation of YWHAZ. These results reveal that FSCN1 may be a key regulator of radioresistance and could be a potential target for improving radiotherapy efficacy in cervical cancer and head and neck cancer patients with PIK3CA alterations.

BackgroundIt has been reported that the development of cervical squamous cell carcinoma (CSCC) requires the involvement of a large number of lncRNAs. In a recent study lncRNA, WT1-AS was been characterized as a tumor-suppressive lncRNA in gastric cancer. In our study we aim to explore the involvement of WT1-AS in CSCC.MethodsSeventy-six CSCC patients (20 to 63 years, 40.1 ± 6.1 year) from the 233 CSCC patients who were admitted by the Affiliated Tumour Hospital of Xinjiang Medical University between august 2010 and January 2014. RT-qPCR, cell proliferation rate measurement, cell transfection, and western blot were carried out to analyze the samples.ResultsWe found that HPV infection failed to affect WT1-AS expression in CSCC tissues, while WT1-AS was down-regulated in CSCC tissues compared with non-cancer tissues. P53 was also down-regulated in CSCC tissues and positively correlated with WT1-AS. Analysis of the survival of CSCC patients revealed that low levels of WT1-AS were accompanied by poor survival. Significantly up-regulated p53 was observed after WT1-AS over-expression in CSCC cells, while p53 over-expression failed to affect WT1-AS. P53 and WT1-AS over-expression resulted in the inhibited proliferation of CSCC cells.ConclusionTherefore, WT1-AS is down-regulated in CSCC and it may inhibit CSCC cell proliferation at least partially by up-regulating p53.

The large sample data of HPV genotypes on cervical squamous cell carcinoma (CSCC) and cervical adenocarcinoma (CAC) tissues are rarely reported in China. This study is aimed to investigate the clinical value of distribution of different kinds of genotypes of human papillomavirus (HPV) within regional (mainly in Jiangsu Province in China) patients of both CSCC and CAC. We collected tissue samples of from 1044 women with CSC (826 cases) and CAC (218 cases) in 29 hospitals of 6 Provinces in China from November 1978 to December 2017. HPV DNA was extracted and 23 genotypes of HPV were detected through the combination of gene-chip and polymerase chain reaction (PCR) technology to analyze distribution of HPV infection types among subjects of CSCC and CAC. Among 1044 cases of CSCC and CAC, 901 were found HPV positive making total HPV detection rate of 86.30% (901/1044). Total detection rate of CSCC was 91.53% (756/826) in which 16, 18, 58, 33, 52, 31 were the most common types where detection frequencies of 16 and 18 types were 56.84% (544/957) and 9.93% (95/957), respectively. Total detection rate of CAC was 66.51% (145/218) in which 16, 18, 31, 33, 52, 58 were the most common types where detection frequencies of 16 and 18 types were 35.29% (84/238) and 32.35% (77/238), respectively. The HPV detection rates were different in female CSCC and CAC tissues of region studied. The 16, 18, 31, 33, 52 and 58 types are the most common genotypes found in two sorts of cervical carcinoma tissues. The detection rate of 16 types was higher than 18 types in CSCC and were very close in CAC tissues. Conducting HPV genotypes detection of CSCC and CAC will help doctors evaluating onset risk of cervical carcinoma and tracking HPV infected patients with high cancerogenic risk. The early detection will play important role in prevention and treatment of female CSCC and CAC in our nation.

To explore the possible influence of deleted in malignant brain tumor 1 (DMBT1) in cervical squamous cell carcinoma (CSCC). DMBT1 expression was detected by Real‐time reverse transcription PCR (qRT‐PCR) and immunohistochemistry in CSCC and adjacent normal tissues from 167 CSCC patients, and its relationship with clinicopathological features and prognosis was analyzed. Besides, the in vitro experiments, including MTT, Cell‐Light EdU, Wound‐healing, Transwell invasion, Annexin V‐FITC/PI staining, qRT‐PCR, and Western blot, were performed in SiHa and CaSKi cells, which were both divided into Blank, Vector, and DMBT1 groups. The mRNA level and the positive expression rate of DMBT1 in CSCC tissues were lower than the adjacent normal tissues. Moreover, DMBT1 positive rate was linked to FIGO stage, tumor diameter, lymph node metastasis, and tumor differentiation of CSCC. Besides, patients with positive DMBT1 expression had higher 5‐year survival rate than those negative ones. According to the in vitro experiments, SiHa and CaSKi cells with overexpressed DMBT1 showed the inhibition of proliferative ability and the enhancement of apoptosis with the upregulated pro‐apoptosis proteins (Bax and Cleaved caspase‐3) and down‐regulated anti‐apoptosis protein Bcl‐2. Moreover, compared with Blank group, DMBT1 group presented decrease in the migration and invasion of SiHa and CaSKi cells with the down‐expression of interstitial markers (N‐cadherin and Vimentin) and the up‐expression of epithelial marker E‐cadherin. DMBT1 was decreased in CSCC, whereas its overexpression can not only inhibit the proliferation, migration, and invasion, but induce the apoptosis of human CSCC cells, being a novel strategy for CSCC treatment.

Background This study aims to investigate the difference in vaginal microecology, local immunity and HPV infection among childbearing-age women with different degrees of cervical lesions. Methods A total of 432 patients were included in this study. Among these patients, 136 patients had LSIL, 263 patients had HSIL and 33 patients had CSCC. These patients were assigned as the research groups. In addition, 100 healthy females were enrolled and assigned as the control group. Results The microbiological indexes of vaginal secretions were evaluated. Furthermore, the concentrations of SIgA, IgG, IL-2 and IL-10 in vaginal lavage fluid, as well as the presence of HPV, mycoplasma and Chlamydia in cervical secretions, were detected. The results is that: (1) Differences in evaluation indexes of vaginal microecology among all research groups and the control group were statistically significant (P

AIM To compare the advantage of image-guided brachytherapy (IGBT) over conventional two-dimensional brachytherapy (2DBT) in patients with advanced cervical squamous cell carcinoma. PATIENTS AND METHODS This study included 253 patients with stage IB2-IVA diseases treated with two schemes of brachytherapy. One hundred and thirty-six patients received 2DBT, whereas 117 patients received IGBT. Tumor stage, age, and tumor diameter were matched between the two groups. Local relapse-free survival, overall survival, and cumulative incidences of gastrointestinal and genitourinary complications were compared between the two groups. RESULTS The overall and local relapse-free survival rates were similar between the two groups. The cumulative rate of grade 2 and higher gastrointestinal complication was 21.3% for the 2DBT group, and 8.5% for the IGBT group (p=0.007), whereas that of grade 2 and higher genitourinary injury was 11.8% for the 2DBT group, and 1.7% for the IGBT group (p=0.002). CONCLUSION In patients with advanced cervical squamous cell carcinoma, IGBT achieves a higher therapeutic ratio compared to 2DBT technique by minimizing the late toxicities.

Background This study was to evaluate the prognostic value of metabolic parameters on F-18-FDG PET/CT and the status of human papillomavirus (HPV) infection and known prognostic variables for predicting tumor recurrence and investigating a prognostic model in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy (CCRT). Methods A total of 129 patients with cervical squamous cell carcinoma who underwent initial CCRT were eligible for this study. Univariate and multivariate analyses were performed using traditional prognostic factors, metabolic parameters, and HPV infection. Classification and regression decision tree (CART) was used to establish new classification. Results Among 129 patients, 29 patients (22.5%) had recurrence after a median follow-up of 60 months (range, 3–125 months). Tumor size, para-aortic lymph node metastasis, nodal SUVmax, and HPV infection status were identified as independent prognostic factors by multivariate analysis. The CART analysis classified the patients into three groups. The first node was nodal SUVmax, and HPV status was the second node for patients with nodal SUVmax ≤7.49; Group A (nodal SUVmax ≤7.49 and HPV positive, HR 1.0), Group B (nodal SUVmax ≤7.49 and HPV negative, HR 3.56), and Group C (nodal SUVmax > 7.49, HR 10.13). Disease-free survival was significantly different among the three groups (p

This study investigated the association of the human 8-oxoguanine glycosylase 1 (hOGG1) Ser326Cys polymorphism with risk of cervical squamous cell carcinoma (CSCC) and high-risk human papilloma virus (HR-HPV) infection.The hOGG1 Ser326Cys polymorphism is reported to be correlated with the risk of several cancers. However, there are reports that have found no significant differences in the frequency of the hOGG1 Ser326Cys between cervical carcinoma patients and controls.hOGG1 Ser326Cys was genotyped through modified allele mismatch amplification polymerase chain reaction in 1200 healthy controls, 400 cervical intraepithelial neoplasia (CIN) grade III cases, and 400 CSCC cases.The homozygous genotype of hOGG1 Cys326Cys (GG) was associated with increased risk of CIN III (odds ratio, OR = 1.81 [1.31-2.49], p 0.001) and CSCC (OR = 3.05 [2.2-4.20], p 0.001). The G allele or G carrier (GG + CG) genotype was a highly-significant risk factor for CSCC (OR = 1.49 [1.14-1.97], p = 0.004). In the HR-HPV-positive group, the homozygous genotype of hOGG1 GG was associated with increased risk of CSCC (OR = 3.66 [2.02-6.62], p 0.001) and risk of CIN III (OR = 1.82 [1.08-3.06], p = 0.024). The proportion of G allele carriers was significantly increased in CIN III (51.9%, [322/620], OR = 1.33 [1.03-1.72], p = 0.028) and CSCC (62.1% [221/356], OR = 2.02 [1.51-2.71], p 0.001). The GG and GC genotypes were consistently identified as significant risk factors for CSCC (OR = 1.73 [1.06-2.83], p = 0.029) in the HR-HPV infected group. We further observed enrichment of the hOGG1 Ser326Cys polymorphism in the CIN III (p = 0.021) and CSCC (p 0.001) stratified by age at first intercourse, with more significant enrichment (p = 0.036) in the HR-HPV infection group.Our findings support associations of the hOGG1 Ser326Cys polymorphism with CSCC carcinogenesis and susceptibility to HR-HPV infection. The hOGG1 Ser326Cys polymorphism may serve as a potential genetic biomarker of susceptibility to cervical cancer and HR-HPV infection.

Introduction: A causal link between infection with a high-risk strain of human papilloma virus (hrHPV) and the development of cervical squamous cell carcinoma (SCC) is well established. However, a small number of SCCs are hrHPV-negative by either HPV co-DNA testing and/or HPV-in situ hybridization (HPV-ISH) at the time of diagnosis. These apparently hrHPV-negative lesions are poorly understood, specifically whether hrHPV-positive precursor lesions exist, which would be detected through hrHPV-based screening. Methods: A search of the pathology archives at the Johns Hopkins Hospital identified women with a diagnosis of hrHPV-negative cervical SCC on surgical specimen. All prior pathologies, including cervical cytology and surgical pathology specimens, and associated hrHPV DNA test results, p16 immunohistochemistry, and HPV-ISH were reviewed. Results: A total of 25 women were identified having a surgical specimen diagnosed as SCC with either negative or equivocal HPV-ISH. Fifteen had a Pap test in the 6 months preceding a diagnosis of SCC, with cytology diagnoses as follows: high-grade squamous intraepithelial lesion n = 14/15; atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion n = 1/15. hrHPV co-testing was performed for 5 of these 15 women and was negative in 2/5 cases. Cervical biopsy was performed for 24 women. HPV-ISH testing, performed on 14 of the biopsy specimens, was negative for 11/14 patients. Of 15 specimens stained for p16, 14 were positive. Conclusion: A subset of patients exist in whom hrHPV is not detectable at or near the time of progression to SCC. Additional research is necessary to further describe this population and determine whether maintaining cytological screening would provide benefit.

Background/Aim. Hypoxia is one of the major changes that occurs in the tumor microenvironment. It has been observed that there are pluripotent cancer cells in the cancer cell population that affect tumor growth and their resistance to therapy. The aim of this study was to examine the expression of hypoxia-inducible factor-1 alpha (HIF-1?), endogenous marker of hypoxia, and SOX2, marker of the pluripotent stem cells existing in the normal adult tissues, in the cervical squamous cell carcinoma (SCC). Methods. The study was conducted in 90 women with invasive cervical SCC, divided into two groups ? 60 women in the Group A, with FIGO IB1 < 20 mm tumors (no metastases in the lymph nodes), and 30 women in the group B with tumors FIGO I?II (positive lymph nodes). The basic clinical parameters were determined by standard histopathological analysis, and the expression of HIF-1? and SOX2 by immunohistochemical examination. Results. There was a significant difference between the groups A and B, in the expression of HIF-1? (p = 0.024), but not in the expression of SOX2 (p = 0.566). Expression of HIF-1? was significantly higher in the group with lymph node metastases and invasion of lymphovascular spaces (p

To assess if intravoxel incoherent motion (IVIM) imaging can be used to predict early response to chemoradiotherapy (CRT) in cervical cancer. IVIM imaging before and during CRT (at doses of 20 and 40 Gy) was performed in 17 patients with cervical squamous cell carcinoma. The percentage changes of IVIM parameters were significantly higher for complete remission (CR) than non-CR groups. IVIM may play a supplementary role for predicting early response to CRT in cervical cancer.

Background: Myeloid-derived suppressor cells (MDSCs) may lead to immune evasion and disease progression in some cancers, but their roles remain to be investigated in cervical cancer. This study aimed to characterize the specific subsets of MDSCs that might be potential indicators for disease progression in cervical cancer patients. Methods: Different subsets of MDSCs were characterized using flow cytometry in blood samples from healthy subjects and cervical cancer patients. T-cell proliferation assay was performed in vitro. Tumor infiltrating CD8+ and FOXP3+ cells were also evaluated by immunostaining on the tumor tissues from patients with early and locally advanced cervical cancer. We further analyzed the relevance of circulating MDSCs to clinicopathological characteristics, patient survival as well as tumor infiltrating lymphocytes. Results: The frequency of circulating GrMDSCs increased correlated with FIGO stage while the percentage of MoMDSCs only elevated in patients with advanced cervical cancers. For patients with early and locally advanced cervical cancer, the frequency of circulating GrMDSCs but not MoMDSCs correlated with clinicopathologic parameters including metastatic lymph nodes, deep stromal invasion and tumor recurrence. The levels of circulating GrMDSCs also negatively correlated with the densities of CD8+ cells in tumor tissues. In vitro assay showed that Gr-MDSCs suppressed the proliferation of autologous T cells. Conclusion: Our study demonstrates that the increased frequency of circulating GrMDSCs is associated with tumor burden and recurrence in early and locally advanced cervical cancer patients, that the GrMDSCs may be potential biomarkers for disease progression cervical cancers.

We downloaded gene expression data, clinical data, and somatic mutation data of cervical squamous cell carcinoma (CSCC) patients from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Predictive lncRNAs were screened using univariate analysis and least absolute shrinkage and selection operator (LASSO) regression, and risk scores were calculated for each patient according to the expression levels of lncRNAs and regression coefficients to establish a risk model that could be a novel signature. We assessed the correlation between immune infiltration status, chemotherapeutics sensitivity, immune checkpoint proteins (ICP), and the signature. Therefore, we selected 11 immune-related lncRNAs (WWC2,AS2, STXBP5.AS1, ERICH6.AS1, USP30.AS1, LINC02073, RBAKDN, IL21R.AS1, LINC02078, DLEU1, LINC00426, BOLA3.AS1) to construct the risk model. Patients who were in the high-risk group had a shorter survival time than those in the low-risk group (p 0.001). Risk scores in the signature were negatively correlated with macrophage M1, macrophage M2, and T cell CD8 + ; what's more, T cell CD8 + was higher in the low-risk group. The expression levels of ICP such as PD-L1, PD-1, CTLA-4, TIGIT, LAG-3, and TIM-3 were substantially higher in the low-risk group. For chemotherapeutic agents, high-risk scores were associated with higher half-inhibitory concentrations (IC50) of cisplatin. These findings suggested that the risk model can be a novel signature for predicting CSCC patients' prognosis, and it also can be used to formulate clinical treatment plans for CSCC patients.

BACKGROUND In recent years, the incidence of cervical cancer has increased with increasing life pressures and changes in women's social roles, posing a serious threat to women's physical and mental health. AIM To explore the clinical effect of Endo combined with concurrent radiotherapy and chemotherapy in the treatment of advanced cervical squamous cell carcinoma. METHODS A total of 120 patients admitted to the oncology department of our hospital were selected as the research subjects. They were equally divided into the test group and the control group (60 patients each) with a random number table. The test group was treated with Endo combined with concurrent radiotherapy and chemotherapy, and the control group was treated with concurrent radiotherapy and chemotherapy. We compared the serum thymidine kinase 1 (TK1), human epididymis protein 4 (HE4), vascular endothelial growth factor (VEGF), and squamous cell carcinoma-associated antigen (SCC-Ag) levels, the clinical effects and survival before and after radiotherapy and chemotherapy, the quality score, and the 3-year follow-up outcomes between the two groups. RESULTS After chemotherapy, the complete remission + partial remission rate was 85.00% in the test group and 68.33% in the control group; the difference was not statistically significant (P > 0.05). Before chemotherapy, the serum TK1, HE4, VEGF, and SCC-Ag levels of the two groups were not significantly different (P > 0.05). After chemotherapy, the levels of serum TK1 (1.27 ± 0.40 pmol/L), HE4 (81.4 ± 24.0 pmol/L), VEGF (235.1 ± 38.0 pg/mL), and SCC-Ag (1.76 ± 0.55 ng/mL) were lower than those in the control group [TK1 (1.58 ± 0.51 pmol/L), HE4 (98.0 ± 28.6) pmol/L, VEGF (284.2 ± 54.1 pg/mL), and SCC-Ag (2.34 ± 0.78 ng/mL)]. The difference was statistically significant (P < 0.05). Before chemotherapy, there were no significant differences in the physical, role, mood, cognition, social and symptom scale scores of the two groups (P > 0.05). After chemotherapy, the physical, role, mood, cognitive and social scores were higher in the test group than in the control group, and the difference was statistically significant (P < 0.05). The symptom scale scores of the test group were all lower than those of the control group, and the difference was statistically significant (P < 0.05). The 3-year progression-free survival (PFS) rate was 43.33% in the test group and 26.67% in the control group; the overall survival (OS) rate was 48.33% in the test group and 33.33% in the control group; the differences were not statistically significant (P > 0.05). The 3-year PFS time of the test group was 20.0 mo, which was longer than that of the control group (15.0 mo), and the difference was significant (P < 0.05). The OS time of the test group was 30.0 mo, which was longer than that of the control group (18.0 mo), and the difference was significant (P < 0.05). CONCLUSION Endo combined with concurrent radiotherapy and chemotherapy for the treatment of advanced cervical squamous cell carcinoma has a positive effect on reducing the level of tumor markers in patients, prolonging the PFS and OS times of patients, and improving the quality of life.

Background: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the second most common type of cancer among gynecologic malignancies worldwide. Chromobox (CBX) family proteins are associated with the regulation of tumorigenesis, metastasis, and evolution of various cancers.Methods: The clinical features, expression levels, and prognostic value of CBXs in CESC were analyzed through several databases, including ONCOMINE, GEPIA, HPA, UALCAN, cBioPortal, Kaplan-Meier plotter, and Metascape.Results: We concluded that the expression level of CBX2/4/8 was upregulated, while the expression level of CBX6/7 was downregulated in CESC specimens. Immune infiltration analysis revealed that CBX1/2/3/4/5/6/8 proteins were downregulated in normal cervical tissues, and upregulated in CESC specimens. In contrast, CBX7 protein expression was significantly higher in normal adjacent cervical tissues and was not detected in CESC tissues. CBX1/3/6 mRNA expression was significantly correlated with the pathological stage of CESC. Prognostic analysis showed that patients with high CBX7 levels of CESC had a favorable prognosis.Conclusions: Our study indicated that CBX7 could be an attractive biomarker for the prognosis of CESC.

The major obstacle to treat cervical squamous cell carcinoma (CSCC) is the high prevalence of metastasis, which severely affects 5-year survival rate and quality of life for cancer patients. The DEAD-box helicase family has been reported to be a critical mediator in the development and metastasis of various cancers. DEAD-box helicase 19A (DDX19A) is a member of the DEAD-box helicase family; however, its functional role in CSCC is unclear. In this study, bioinformatics analysis of clinical samples from public databases demonstrated that the expression of DDX19A was elevated in CSCC tissues and that high expression of DDX19A was positively correlated with metastasis and poor clinical outcome. Functionally, we found that DDX19A promoted CSCC cell migration and invasion in vitro and lung metastasis in vivo. Mechanistically, overexpression of DDX19A increased NADPH oxidase 1 (NOX1) expression, enhanced reactive oxygen species (ROS) production, and induced the migration and invasion of CSCC cells. Rescue experiments revealed that DDX19A-induced CSCC functional alterations were dependent on NOX1 and that DDX19A-promoted CSCC metastasis was abrogated upon the inhibition of ROS. Our results demonstrated that DDX19A could promote CSCC metastasis by inducing NOX1-mediated ROS production and that blockage of the NOX1/ROS axis might serve as a potential therapeutic target for patients with DDX19A-overexpressed CSCC.

Background The expression of tumor suppressor candidate 3 (TUSC3) is associated with proliferation in several types of cancer, leading to an unfavorable prognosis. The present study aimed to assess the cellular and molecular function of TUSC3 in patients with cervical squamous cell carcinoma (CSCC). Methods Levels of mRNA expressions of TUSC3 were analyzed in CSCC tissues and six cell lines using qRT-PCR. Immunohistochemistry(IHC) was used to evaluate the protein expression level of TUSC3 in four paired specimens, 220 paraffin-embedded CSCC specimens and 60 cases of normal cervical tissues(NCTs), respectively. Short hairpin RNA interference was employed for TUSC3 knockdown. Cell proliferation, migration and invasion was evaluated using growth curve, MTT assay, wound healing and transwell assay respectively. Results The results demonstrated that TUSC3 mRNA and protein expression levels were down-regulated in CSCC samples. Multivariate and univariate analyses indicated that TUSC3 was an independent prognostic factor for patients with CSCC. Decreased TUSC3 expression levels were significantly associated with proliferation and an aggressive phenotype of cervical cancer cells. Moreover, the knockdown of TUSC3 promoted migration and invasion of cancer cells, while the increased expression of TUSC3 exhibited the opposite effects. The down-regulation of TUSC3 facilitated proliferation and invasion of CSCC cells through the activation of the AKT signaling pathway. Conclusions Our data demonstrated that the down-regulation of TUSC3 promoted CSCC cell metastasis via the AKT signaling pathway. Therefore, TUSC3 may serve as a novel prognostic marker and potential target for CSCC.

Aim: To better predict the survival of cervical squamous cell carcinoma (CESC) patients, we aimed to construct a signature according to different immune infiltration. Methods: We downloaded the RNA sequences of CESC patients from the Cancer Genome Atlas database. By using single-sample gene set enrichment analysis, we separated the samples into high- and low-immunity groups. Then we separated the samples into training and testing datasets and performed the following analyses: univariate, least absolute shrinkage and selection operator analysis, multivariate Cox regression analyses and weighted gene coexpression network analysis using R software. Gene ontology and Kyoto Encyclopedia of Genes and Genomes studies were performed using the Database for Annotation, Visualization and Integrated Discovery website. Results & conclusion: We finally identified a signature with three mRNAs and two lncRNAs: ADGRG5, HSH2D, ZMAT4, RBAKDN and LINC00200. In short, our study constructed an mRNA–lncRNA signature related to immune infiltration to better predict the survival of CESC patients.

Objective: Immunity plays a vital role in the human papilloma virus (HPV) persistent infection, and closely associates with occurrence and development of cervical squamous cell carcinoma (CSCC). Herein, we performed an integrated bioinformatics analysis to establish an immune-gene signature and immune-associated nomogram for predicting prognosis of CSCC patients.Methods: The list of immunity-associated genes was retrieved from ImmPort database. The gene and clinical information of CSCC patients were obtained from The Cancer Genome Atlas (TCGA) website. The immune gene signature for predicting overall survival (OS) of CSCC patients was constructed using the univariate Cox-regression analysis, random survival forests, and multivariate Cox-regression analysis. This signature was externally validated in GSE44001 cohort from Gene Expression Omnibus (GEO). Then, based on the established signature and the TCGA cohort with the corresponding clinical information, a nomogram was constructed and evaluated via Cox regression analysis, concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots and decision curve analyses (DCAs).Results: A 5-immune-gene prognostic signature for CSCC was established. Low expression of ICOS, ISG20 and high expression of ANGPTL4, SBDS, LTBR were risk factors for CSCC prognosis indicating poor OS. Based on this signature, the OS was significantly worse in high-risk group than in low-risk group (p-value < 0.001), the area under curves (AUCs) for 1-, 3-, 5-years OS were, respectively, 0.784, 0.727, and 0.715. A nomogram incorporating the risk score of signature and the clinical stage was constructed. The C-index of this nomogram was 0.76. AUC values were 0.811, 0.717, and 0.712 for 1-, 3-, 5-years OS. The nomogram showed good calibration and gained more net benefits than the 5-immune-gene signature and the clinical stage.Conclusion: The 5-immune-gene signature may serve as a novel, independent predictor for prognosis in patients with CSCC. The nomogram incorporating the signature risk score and clinical stage improved the predictive performance than the signature and clinical stage alone for predicting 1-year OS.

Background: Cervical squamous cell carcinoma (CESC) is one of the most frequent malignancies in women worldwide. The level of immune cell infiltration and immune-related genes (IRGs) can significantly affect the prognosis and immunotherapy of CESC patients. Thus, this study aimed to identify an immune-related prognostic signature for CESC.Methods: TCGA-CESC cohorts, obtained from TCGA database, were divided into the training group and testing group; while GSE44001 dataset from GEO database was viewed as external validation group. ESTIMATE algorithm was applied to evaluate the infiltration levels of immune cells of CESC patients. IRGs were screened out through weighted gene co-expression network analysis (WGCNA). A multi-gene prognostic signature based on IRGs was constructed using LASSO penalized Cox proportional hazards regression, which was validated through Kaplan–Meier, Cox, and receiver operating characteristic curve (ROC) analyses. The abundance of immune cells was calculated using ssGSEA algorithm in the ImmuCellAI database, and the response to immunotherapy was evaluated using immunophenoscore (IPS) analysis and the TIDE algorithm.Results: In TCGA-CESC cohorts, higher levels of immune cell infiltration were closely associated with better prognoses. Moreover, a prognostic signature was constructed using three IRGs. Based on this given signature, Kaplan–Meier analysis suggested the significant differences in overall survival (OS) and the ROC analysis demonstrated its robust predictive potential for CESC prognosis, further confirmed by internal and external validation. Additionally, multivariate Cox analysis revealed that the three IRGs signature served as an independent prognostic factor for CESC. In the three-IRGs signature low-risk group, the infiltrating immune cells (B cells, CD4/8 + T cells, cytotoxic T cells, macrophages and so on) were much more abundant than that in high-risk group. Ultimately, IPS and TIDE analyses showed that low-risk CESC patients appeared to present with a better response to immunotherapy and a better prognosis than high-risk patients.Conclusion: The present prognostic signature based on three IRGs (CD3E, CD3D, LCK) was not only reliable for survival prediction but efficient to predict the clinical response to immunotherapy for CESC patients, which might assist in guiding more precise individual treatment in the future.

OBJECTIVE The aim of the study was to assess the applicability and safety of cervical cancer screening guidelines recommended by the American College of Obstetricians and Gynecologists (2016) and American Society for Colposcopy and Cervical Pathology (2019) for women with solid organ transplants (SOTs). MATERIALS AND METHODS We analyzed data previously abstracted through December 2015 for 971 women (18-60 y) who received their first SOT at Mayo Clinic (Rochester, MN) from January 17, 1995, through December 31, 2011. Inclusion criteria were initial benign findings on cervical cytology after SOT and at least 1 subsequent cytologic screening. RESULTS Of 415 women whose initial cytologic findings were benign, 310 met inclusion criteria. The cumulative incidence of abnormal cervical cytology among these 310 women was 4.3% (95% CI = 1.9%-6.7%) by 30 months and 11.2% (95% CI = 7.1%-15.4%) by 60 months after their initial benign results. Considering all women with SOT, 68.4% (284/415) had no documented abnormal cytologic findings within 60 months (26 had abnormality; 284 no abnormality; and 105 not assessed). In women with negative tests for human papillomavirus, high-grade squamous intraepithelial lesions were not documented on cytology with variable duration of follow-up. No cervical squamous cell carcinoma was identified. CONCLUSIONS Of women with initial benign cervical cytology after SOT, more than two thirds would have been eligible for extended-interval screening. Further study is needed, particularly regarding the role of high-risk human papillomavirus testing.

Huizhen Zhang,1 Shuangling Jin,1 Aifang Ji,2 Ying Ma,3 Chunyan Zhang,1 Ailan Wang,1 Rui Wang1 1Department of Gynecology, Heping Hospital Affiliated to Changzhi Medical College, Changzi, Shanxi Province, 046000, People’s Republic of China; 2Department of Clinical Laboratory, Heping Hospital Affiliated to Changzhi Medical College, Changzi, Shanxi Province, 046000, People’s Republic of China; 3Department of Obstetrics, Heping Hospital Affiliated to Changzhi Medical College, Changzi, Shanxi Province, 046000, People’s Republic of ChinaCorrespondence: Shuangling JinDepartment of Gynecology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi City, Shanxi Province, 046000, People’s Republic of ChinaEmail nj6077@163.comBackground: SLC16A1-AS1 has been characterized as an oncogenic long non-coding (lncRNA) in breast cancer and bladder cancer, while its role in cervical squamous cell carcinoma (CSCC) is unknown.Methods: CSCC and non-tumor tissue samples were collected from 60 female patients, and qPCR was performed to detect the expression of SLC16A1-AS1, miR-194 and SOCS2. Luciferase reporter assay was performed to detect the interaction between SLC16A1-AS1 and miR-194. Colony formation assay was used to detect cell proliferation.Results: SLC16A1-AS1 was down-regulated in CSCC and correlated with poor survival. Overexpression of SLC16A1-AS1 could inhibit the proliferation of cervical cancer cells. In addition, SLC16A1-AS1 could sponge miR-194 and increase the expression levels of SOCS2, ultimately inhibiting the proliferation of cervical cancer cells.Conclusion: SLC16A1-AS1 was downregulated in CSCC and suppressed cell proliferation in cervical squamous cell carcinoma (CSCC) through the miR-194/SOCS2 axis.Keywords: cervical squamous cell carcinoma, SLC16A1-AS1, miR-194, SOCS2

As the second most common female malignant tumor, cervical cancer is also one of the most preventable and avoidable cancers. The World Health Organization has launched a global plan to accelerate the elimination of cervical cancer. Therefore, in the era of postvaccine, the role of HPV subtypes in cervical precancerous lesions and cervical cancer that are not covered by vaccine should be further discussed. The purpose of this study was to explore the role of HPV subtypes not covered by the nine-valent vaccine in high-grade cervical precancerous lesions and cervical cancer.A retrospective analysis was performed on the clinical data of 5220 patients with an HPV infection who were diagnosed and treated in the Department of Gynecology of Shanghai General Hospital between October 2016 and February 2020. In addition, the clinical characteristics of the biopsy results of 470 cases of cervical intraepithelial neoplasia (CIN) 2-3 and 205 cases of cervical squamous cell carcinoma were analyzed.Among patients with HPV subtype infection not covered by the nine-valent vaccine, univariate analysis showed that compared with patients with CIN 2-3, age ≥ 50, not using condom and TCT reported as ASC-H were risk factors for cervical squamous cell carcinoma (P0.05). The detection rates of HPV subtype not covered by the nine-valent vaccine in CIN 2-3 and cervical squamous cell carcinoma patients were 7.23% and 6.34%, respectively.In patients with CIN 2-3 and cervical squamous cell carcinoma, the infection rates of HPV subtype not covered by the nine-valent vaccine were 7.23% and 6.34%, respectively. With the increasing popularity of the vaccine, the infection rates of the corresponding HPV subtype decreased; however, HPV subtype infection not covered by the nine-valent vaccine should not be ignored.

Background: High-risk HPV(hr-HPV) infection is important for the development of invasive cervical cancer. As a developing country with the largest population in the world, China has a great burden of cervical cancer. The cervical cancer screening strategies consisted of cytology and virology, which has been studied by HPV-typing test and HPV-DNA quantitative test since decades ago. The cervical cancer incidence rate has been declined due to the early treatment of precancerous lesions, but postoperative HPV infection is still an issue for cervical cancer patients. This study aims to investigate the association between HPV infection status and recurrence of early-stage cervical cancer through a novel PCR-based HPV test, which could do both HPV typing-test and DNA quantitative-test. Methods: Patients diagnosed with cervical cancer staged IB1- IIA2, who were treated by radical hysterectomy and lymphadenectomy at Cancer Hospital Chinese Academy of Medical Sciences(CAMS) between January 2014 and December 2016 were accrued. The clinicopathological factors, pre- and post-operative HPV infection status, and the prognosis were investigated. Cox regression was used to identify factors associated with LRFS, MFS and OS. Results: A total of 312 patients were enrolled in this study, who were treated by radical resection and accepted pre- and post-operative HPV tests, with a median follow-up time of 60 months(range 14~79 months). The 5-year LRFS rate, MFS rate, and OS rate were 97.8%, 98.4%, and 98.7%. The pre-operative HPV infection rate was 85.3%(266/312), 74 patients had a high level of HPV-DNA(>5x106 copy number/104 cells). Twenty-nine patients had a postoperative persistent high level of HPV-DNA(9.3%). Postoperative persistent high level of HPV-DNA within 12 months(p=0.013), postoperative persistence of HPV-16/18 within 24 months(p=0.004), and deep stromal invasion(>2/3)(p=0.007) were associated with a poor LRFS.Conclusion: Pre-operative HPV-16/18 infection and high level of HPV-DNA were not associated with local recurrence of cervical cancer. Most initial HPV-positive patients had HPV cleared within 24 months postoperatively. Postoperative HPV-16/18 persistence within 24 months, postoperative persistence of high HPV-DNA level within 24 months, and deep stromal invasion(>2/3) were independent risk factors for local recurrence of cervical cancer.

ObjectiveThe clinical data of more than 900 patients with locally advanced cervical squamous cell carcinoma diagnosed for the first time and treated with radical chemoradiotherapy in recent 9 years were analyzed to find important prognostic factors in advanced cervical squamous cell carcinoma, and provide statistics for future research. MethodThe patients were divided into two groups: chemoradiotherapy resistant group and chemoradiotherapy sensitive group. The survival rate and prognostic factors were analyzed using R language. ResultThere was considerable difference in overall survival (OS) and progression free survival (PFS) between the two groups, of which the chemoradiotherapy sensitive group is about 10 months longer than the resistant group. In the chemoradiotherapy resistant group, there were more patients with higher staging, higher NLR(neutrophil to lymphocyte ratio), lymph node metastasis, and a total radiotherapy time of more than 8 weeks. For the factors affecting chemoradiotherapy sensitivity, radiotherapy alone rather than simultaneous chemoradiotherapy, late tumor stage, lymph node metastasis and a total time of radiotherapy more than 8 weeks predicts lower sensitivity. ConclusionThe main clinical factors affecting chemoradiotherapy sensitivity were tumor stage, lymph node metastasis and the total time of radiotherapy. Chemoradiotherapy sensitivity, tumor diameter, NLR, PLR (platelet to lymphocyte ratio) and total time of radiotherapy were independent prognostic factors for OS and PFS.