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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.

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.

Background Cervical cancer (CC) is the primary cause of death in women. This study sought to investigate the potential mechanism and prognostic genes of CC. Methods We downloaded four gene expression profiles from GEO. The RRA method was used to integrate and screen differentially expressed genes (DEGs) between CC and normal samples. Functional analysis was performed by clusterprofiler. We built PPI network by Search Tool for the Retrieval of Interacting Genes Database (STRING) and selected hub modules via Molecular COmplex Detection (MCODE). CMap database was used to find molecules with therapeutic potential for CC. The hub genes were validated in GEO datasets, Gene Expession Profiling Interactive Analysis (GEPIA), immunohistochemistry, Cox regression analysis, TCGA methylation analysis and ONCOMINE were carried out. ROC curve analysis and GSEA were also performed to describe the prognostic significance of hub genes. Results Functional analysis revealed that 147 DEGs were significantly enriched in binding, cell proliferation, transcriptional activity and cell cycle regulation. PPI network screened 30 hub genes, with CDK1 having the strongest connectivity with CC. Cmap showed that apigenin, thioguanine and trichostatin A might be used to treat CC(P P p = 0.037). Cox regression analysis showed that SNX10 and PTGDS were independent prognostic indicators for OS among CC patients (P = 0.007 and 0.003). Conclusions PTGDS and SNX10 showed abnormal expression and methylation in CC. Both genes might have high prognostic value of CC patients.

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

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.

In this article, we investigated prevalence and distributed types of human papillomavirus (HPV) among female cervical squamous cell carcinoma patients in eastern China (mainly in Jiangsu Province). Tissue samples of total 1021 cases with cervical squamous cell carcinoma were incurred from female patients passing through biopsy or surgery. HPV DNA and genotypes of all subjects were examined using polymerase chain reaction (PCR) and gene-chip. There were 937 positive cases among 1021 cervical squamous cell carcinoma tissue samples with the total HPV infection rate of 91.77%. The HPV infection rate of single type was 75.42%. The predominant types of single infection with HPV were HPV 16 (52.60%), HPV 18 (5.19%), HPV 58 (4.51%), HPV 52 (2.84%), HPV 31 (2.74%), HPV 33 (2.45%), HPV 59 (1.76%) and HPV 45 (0.88%). The HPV infection rate of multiple types was 16.35%. The predominant types of multiple infection with HPV were HPV 16+18 (19.16%), 16+58 (6.59%),16+52 (5.99%), 16+33 (5.39%), 11+16 (2.99%), 16+31 (2.99%), 16+45 (2.99%), 16+42 (2.40%) and 16+59 (2.40%). Cervical squamous cell carcinomas had a close relationship with HPV infection. HPV 16, 18, 58, 52, 31, 33, 59, 45 with high prevalence in the cervical squamous cell carcinoma deserve great attention in eastern China (mainly in Jiangsu Province). The protection spectrum of divalent vaccine and ninevalent vaccine were, respectively, 68.52% (642/937) and 90.82% (851/937) in the cases of cervical squamous cell carcinomas.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

Background We investigated the expression and clinical significance of miR-141 and miR-340 in cervical squamous cell carcinoma (CSCC). Methods Expression of miR-141 and miR-340 in CSCC, high-grade squamous intraepithelial lesion (HSIL), and normal cervical squamous epithelium were detected by qRT-PCR. PTEN was assessed by immunohistochemistry. Their relationship with clinicopathological features was analyzed. Results The changes of miR-141 and miR-340 were different in CSCC, HSIL, and normal squamous epithelium (P = 0.030). miR-141 expression was statistically significant in gross type, differentiation, uterine corpus invasion, nerve invasion, vagina invasion, and FIGO stage in CSCC (P < 0.05). miR-340 expression was related to tumor size, differentiation, nerve invasion, lymph node metastasis, and FIGO stage in CSCC (P < 0.05). miR-141 and miR-340 expressions were statistically significant in different ages (P < 0.05) in HSIL. The AUC of miR-141 in CSCC diagnosis and that of miR-340 in HSIL diagnosis were 0.893 and 0.764, respectively. The sensitivity and the specificity of miR-141 for diagnosis of CSCC were 95.0% and 60.8%, respectively, while those of miR-340 for diagnosis of HSIL were 90.0 and 48.6%, respectively. miR-141 and miR-340 expressions are associated with PTEN expression (P = 0.002 and P < 0.001). Conclusion miR-141 and miR-340 may be associated with their target gene PTEN and involved in the carcinogenesis of cervical squamous epithelium.

Squamous cell carcinoma (SCC) of the colon is a rare malignant tumor occurring as either a primary or secondary lesion. Few cases of metastatic or secondary colonic SCC have been published. We report an unusual case of a 59-year-old female patient who was treated by Wertheim hysterectomy and adjuvant chemoradiation for stage IIB SCC of the uterine cervix. Two years later, she developed a metastatic location in the caecum causing an acute intestinal obstruction. She underwent an emergency open right hemicolectomy with ileocolic anastomosis and resection of two nodules of the umbilicus and the right parietal peritoneum. Histopathological examination confirmed a triple metastatic location of SCC. She is disease-free 11 months after surgery. We discuss the clinicopathological features, management strategies, and the prognosis of this rare entity.

Objectives To develop nomograms to assess prognostic factors for 5-year overall survival (OS) and 5-year progression-free survival (PFS) in locally advanced cervical squamous cell carcinoma (LACSC). Methods Overall, 618 patients with LACSC were included in this retrospective analysis. Nomograms for 5-year OS and PFS were developed based on Cox proportional hazards regression models. Concordance index (C-index) and calibration curves were used to define the predictive and discriminatory capacity of the nomogram. A comparison between the nomogram and the International Federation of Gynecology and Obstetrics (FIGO) staging system was conducted using time-dependent receiver operating characteristic (tROC) and area under the curve (tAUC). Results Multivariate analysis identified several prognostic factors for OS including squamous cell carcinoma antigen (SCC-Ag), body mass index (BMI), tumor size, pelvic wall involvement, and para-aortic lymph node metastasis (PALNM). Prognostic factors for PFS included BMI, hemoglobin (HGB), tumor size, pelvic wall involvement, pelvic lymph node metastasis (PLNM) and PALNM. Following bootstrap correction, the C-index of OS and PFS was 0.713 and 0.686, respectively. These nomograms showed superior performance compared with the FIGO 2009 and 2018 staging schema. Conclusions Nomograms were developed to identify prognostic factors for 5-year OS and PFS in patients with LACSC. These nomograms showed good prognostication and are more comprehensive in predicting survival outcomes than existing staging criteria.

Purpose The aim of this study was to explore the effective immune scoring method and mine the novel and potential immune microenvironment-related diagnostic and prognostic markers for cervical squamous cell carcinoma (CSSC). Materials and Methods The Cancer Genome Atlas (TCGA) data was downloaded and multiple data analysis approaches were initially used to search for the immune-related scoring system on the basis of Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm. Afterwards, the representative genes in the gene modules correlated with immune-related scores based on ESTIMATE algorithm were further screened using Weighted Gene Co-expression Network Analysis (WGCNA) and network topology analysis. Gene functions were mined through enrichment analysis, followed by exploration of the correlation between these genes and immune checkpoint genes. Finally, survival analysis was applied to search for genes with significant association with overall survival and external database was employed for further validation. Results The immune-related scores based on ESTIMATE algorithm was closely associated with other categories of scores, the HPV infection status, prognosis and the mutation levels of multiple CSCC-related genes (HLA and TP53). Eighteen new representative immune microenvironment-related genes were finally screened closely associated with patient prognosis and were further validated by the independent dataset GSE44001. Conclusion Our present study suggested that the immune-related scores based on ESTIMATE algorithm can help to screen out novel immune-related diagnostic indicators, therapeutic targets and prognostic predictors in CSCC.

Purpose Squamous cell carcinomas and adenocarcinomas are the most common types of cervical cancer. Compared to squamous cell carcinomas, adenocarcinomas are more common in younger women and have a poorer prognosis. Yet, so far, no useful biomarkers have been developed for these two types of cancer. In the following study, we examined the combination of cytokeratin 5/6, p63, p40 and MUC5AC for distinguishing squamous cell carcinoma (SCC) from adenocarcinoma of the cervix (AEC). Materials and methods A total of 101 SCC and 108 AEC were collected. Immunohistochemical analyses were conducted to determine the expression of CK5/6, p63, p40, CK7 and MUC5AC. One pathologist who was blinded to the patient’s clinical and pathological data interpreted the staining results. Results MUC5AC and CK7 were detected in 81.48 and 82.41% of AEC cases compared to 9.9 and 49.50% of SCC cases (P P = 0.036) and was not related to the prognosis of cervical adenocarcinoma and subtypes. Conclusions MUC5AC may be useful as a biomarker for differential diagnoses between squamous carcinoma and adenocarcinoma of the cervix.

Background Our aim was to investigate the value of serum squamous cell carcinoma (SCC) antigen levels in predicting chemosensitivity, lymph node metastasis, as well as prognosis in patients with cervical squamous cell carcinoma who received neoadjuvant chemotherapy (NACT). Methods This retrospective study enrolled 103 patients with cervical squamous cell carcinoma and then compared the SCC antigen levels between patients who underwent NACT followed by radical surgery (NACT group) and those who underwent radical surgery alone (conventional group), and a correlation analysis between SCC antigen levels and chemosensitivity, lymph node metastasis, or survival time was conducted. Results The SCC antigen levels changed after NACT and were associated with chemosensitivity. Moreover, the optimal cut-off value of the percentage decrease in SCC antigen level after the first chemotherapy (FSCC (%)) was 42.0%, which could be used for assessment of chemosensitivity. The rate of positive lymph nodes in patients with pretreatment SCC antigen levels ≥3.9 ng/mL was significantly decreased after NACT. The overall survival (OS) of NACT group was significantly longer than that of conventional group when the pretreatment SCC antigen levels were ≥ 4.55 ng/mL. The OS and progression-free survival rates of patients with SCC antigen levels

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.

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.

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

Objective The aim of this systematic review and meta-analysis was to pool association effects of serum squamous cell carcinoma antigen (SCC-Ag) on recurrence and mortality in mainly squamous cell cervical cancer patients. Methods MEDLINE and Scopus databases were searched up to June 29, 2016. Studies assessing effects of SCC-Ag on recurrence and death in cervical cancer patients were included. Data extraction was independently performed by two reviewers. A meta-analysis was applied for pooling the effects (i.e., risk ratio (RR), hazard ratio (HR), and unstandardized mean difference (USMD)) of SCC-Ag measured before and after treatment on recurrence and death. Results A total of 61 studies were included. For pretreatment SCC-Ag and recurrence, the pooled RR, HR, and USMD for high versus low serum SCC-Ag were 2.44(95% CI: 1.91, 3.13), 2.23(95% CI: 2.03, 2.45), −7.7(95% CI: -31.7, 16.4), respectively. The corresponding effects for the posttreatment period were 3.91(95% CI: 2.96, 5.16), 3.14(95% CI: 1.29, 7.65), and 3.2(95% CI: -10.6, 17.0), respectively. In addition, patients with high level of pretreatment serum SCC-Ag were also at a higher risk for death than patients with low serum SCC-Ag with a pooled RR of 3.66(95% CI: 2.24, 5.98), pooled HR of 2.50(95% CI: 1.85, 3.37), and pooled USMD of 7.10(95% CI: 4.26, 9.94). The posttreatment serum SCC-Ag effects also reflected a similar trend. Conclusions The serum SCC-Ag was consistently associated with recurrence and mortality of newly diagnosed cervical cancer. This marker may be useful in monitoring disease progression in cervical cancer patients. Prospero registration number is: CRD42016044024.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 55-year-old postmenopausal woman, gravida 5 para 5, with past medical history significant for hypertension, presented to the emergency department with profuse vaginal bleeding and a hemoglobin level of 9 g/dL. The biopsy from an irregular 6-cm cervical mass was consistent with moderately differentiated cervical squamous cell carcinoma. The physical examination did not reveal vaginal or parametrial extension of the tumor. Pelvic magnetic resonance imaging disclosed the known carcinoma, as well as a 9.2 × 7.7 × 6.7 cm anterior uterine fibroid (Fig 1). A staging positron emission tomography scan was negative for metastatic disease. After blood transfusion and vaginal packing, the patient was referred to discuss the immediate management of her newly diagnosed bleeding bulky cervical cancer. In the absence of parametrial or vaginal extension and in the absence of lymph node metastasis (both on clinical examination and imaging), she was classified as having International Federation of Gynecology and Obstetrics stage IB2 disease.

Long non-coding RNAs (lncRNAs), which have little or no protein-coding capacity, caught a particular interest since their potential roles in the cancer paradigm. As the most common cancer in women, cervical squamous cell carcinoma remains one of the leading causes of deaths from cancer. However, limited evidence is available to determine the role of lncRNAs in the prognosis of cervical squamous cell carcinoma. In this study, we collected lncRNA expression profiling to identify prognosis related lncRNAs for cervical squamous cell carcinoma from TCGA database. In addition, we developed a 15-lncRNA signature based risk score to comprehensively assess the prognostic function of lncRNA. Furthermore, we performed a ROC analysis to identify the optimal cut-off point for classification risk level of the patients. Univariate Cox regression models were used to assess the association between lncRNAs and prognosis of patients with cervical squamous cell carcinoma. A 15-lncRNA based risk score was developed based on the Cox co-efficient of the individual lncRNAs. The prognostic value of this risk score was validated in the complete set and internal testing set. In summary, a 15-lncRNA expression signature (BAIAP2-AS1, RP11-203J24.8, LINC01133, RP1-7G5.6, RP11-147L13.15, SERHL, CTC-537E7.3, RP11-440L14.1, RP11-131N11.4, ILF3-AS1, RP11-80H18.4, RP11-1096G20.5, CTD-2192J16.26, RP11-621L6.3, and RP11-571M6.18) were identified and validated which can predict cervical cancer patient survival. The potential functions of this 15-lncRNA expression signature and individual lncRNAs as prognostic targets of cervical cancer were revealed by this study. Furthermore, these findings may have important implications in the understanding of the potential therapeutic method for the cervical squamous cell carcinoma patients.

Cervical cancer is one of the commonest cancers worldwide, especially in developing countries. In early stage disease, a variety of pathological parameters are of prognostic value but currently this does not include tumour grade which, for a number of reasons, is of limited or no value in cervical squamous cell carcinomas. In a recent article in this journal, Jesinghaus and colleagues investigated a novel histopathological grading system based on tumour budding and cell nest size, which has been shown to outperform conventional grading systems for squamous cell carcinoma at several other sites such as lung, oral cavity, and oesophagus in terms of patient prognostication. They tested the prognostic value of this grading system in two independent cohorts of cervical squamous cell carcinoma. The grading system proved to be a highly effective, stage-independent prognosticator in both cohorts with small cell nest size and high tumour budding indicative of a poor prognosis. It is hoped that the results of this study will be validated in additional independent larger cohorts and will act as an impetus for the development of a meaningful and easy-to-implement grading system for cervical squamous cell carcinoma. As comparable tumour budding/cell nest size-based grading systems have been shown to be of prognostic value for squamous cell carcinomas at other sites, this shows the potential of these parameters to serve as the basis for a common grading system applicable to squamous cell carcinomas of different anatomic sites.

Background: Cervical cancer is one of the most frequently occurring malignancies in women worldwide, with high mortality rates. Cervical Squamous Cell Carcinoma (SCC) presents previous states of non-invasive precursor lesions, and early stage Low-Grade Squamous Intraepithelial Lesions (LSIL) regress to normal or Atypical Squamous Cells of Undetermined Significance (ASCUS) in approximately 50% of cases. Deleted in Malignant Brain Tumors 1 (DMBT1) is a tumour suppression glycoprotein, which absence is considered a malignancy marker in many epithelial cancers. Objective: To analyse DMBT1’s presence and localization in SCC and precursor lesions. Method: Immunohistochemistry for DMBT1 was performed in cervix biopsies classified as normal, LSIL, HSIL and SCC. Results: DMBT1 was detected at the supranuclear and sometimes infranuclear regions of the endocervix monolayer epithelial cells in normal and HSIL biopsies. In LSIL samples the detection of DMBT1 in endocervix was variable between patients. Also variable was DMBT1 staining in cells of glandular epithelium. The glycoprotein was not detected in the stratified epithelium of the exocervix, regardless of the lesion grade; nor in dysplastic cells. Conclusion: The absence of DMBT1 from endocervix only in some samples of LSIL is promising as a candidate for possible lesion regression potential marker. Fil: Valero, Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Roldán, María Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Ruiz, Maria Fernanda. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Teijeiro, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - Rosario. Unidad de Direccion; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Marquez, Susana Beatriz. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Marini, Patricia Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina

Objectives: To compare immunohistochemical detection of Human chorionic gonadotropin (hCG) expression in paraffin embedded tissue of squamous cell carcinomas (SCC) and high grade squamous intraepithelial lesions (HSIL). Methods: The samples in this retrospective study were obtained from the archives of the Pathology Department at Gaziantep University, Gaziantep, Turkey, over the period from January 2012 to September 2016. The study group consisted of 55 cases of SCC and 45 cases of HSIL. Tissue expression of hCG was detected by specific binding of anti-hCG antibody using an automated immunohistochemistry staining device. The categorical variables of intensity and coverage were analyzed statistically using Pearson Chi-Square test. Results: High grade squamous cell lesions cases showed weak (84.4%, n=38/45) to no (15.6%, n=7/45) staining for hCG. None of the HSIL cases showed strong positivity. Strong positivity for hCG was detected in 90.9% (n=50/55) of SCC cases. Conclusion: Our study supports the association of ectopic hCG expression in cancer pathogenesis by demonstrating strong hCG immunoreactivity only in SCC cases. This finding can be helpful in supporting the diagnosis of invasive carcinoma in small or fragmented biopsies, which can on their own be confusing for the pathologists.

Cervical leiomyosarcoma is known to be rare from the previous reviews of a large number of malignant cervical tumors. The patient was a 66-year-old woman with irregular vaginal bleeding. She underwent modified radical hysterectomy and bilateral salpingooophorectomy. Histopathologically, we diagnosed the coexistence of uterine cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ with endometrial lesions that had continuous and skip patterns and fallopian tubal lesions with a partial lesion. To the best of our knowledge, cases of synchronous leiomyosarcoma and cancers have not often been reported; only two cases of synchronous cervical leiomyosarcoma and cervical squamous cell carcinoma have been published. This case is the first presentation of coincidental primary cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ. Additionally, we considered cervical gastric-type adenocarcinoma in situ with continuous lesions on the endometrium and skip lesions on the left fallopian tube.

// Lei Wang 1, 2, 6, * , Xing Cheng Wang 2, 6, * , Xinyu Li 3, 6, * , Yan Gu 4 , Jun Zhou 1 , Shuwan Jiang 1 , Jiajia Liu 1 , Chong Wu 1, * , Zhiyan Ding 1 , Yafeng Wan 2, 6, * and Chenghai Wang 1, 2, 4, 5, 6 1 Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, China 2 Department of Pharmacy, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China 3 Department of Basic Medical, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China 4 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China 5 Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu 225001, China 6 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China * These authors contributed equally to this work Correspondence to: Chenghai Wang, email: 429350063@qq.com Keywords: gynecological cancers; cervical squamous cell carcinoma; endometrial adenocarcinoma; uc.189; prognosis Received: April 04, 2017 Accepted: December 23, 2017 Published: December 29, 2017 ABSTRACT In recent decades, emerging evidence demonstrates that ultraconserved elements (UCEs) encoding noncoding RNAs serve as regulators of gene expression. Until now, the role of uc.189 in human cancers remains undefined and the clinical significance of uc.189 in gynecological cancers remains unknown. This study was to identify the prognostic value of uc.189 expression in gynecological cancers. Tissue microarrays were constructed with 243 samples including 116 cervical squamous cell carcinomas (CSCCs), 98 endometrial adenocarcinomas (EACs), 29 ovarian cystoadenocarcinomas(OCAs), and corresponding normal tissues. In CSCC, uc.189 expression was increased in 78.5% of cases (91/116), decreased in 4.3% (5/116), and unchanged in 17.2% (20/116). In EAC its expression was increased in 74.5% (73/98), decreased in 3.1% (3/98), and unchanged in 22.4% (22/98). Expression of uc.189 was increased in 23, and unchanged/decreased in 6, of 29 cases of ovarian cystoadenocarcinomas. Univariate and multivariate Cox regression analysis demonstrated that over-expression of uc.189 predicted poor prognosis in CSCC and EAC. Thus, these findings suggested uc.189 might be an evaluating prognosis marker of gynecological tumors.

The therapeutic significance of neoadjuvant chemotherapy (NAC) followed by radiation therapy (RT) was negated during the early 1990s. Here, we compared post-NAC RT to surgery for chemo-sensitive cervical squamous cell carcinoma (SCC). This study included 79 consecutive patients with cervical SCC who were treated by NAC followed by surgery (n = 49) or by definitive RT (n = 30). We compared characteristics and survival outcomes between the surgery and RT groups by their responses to NAC. Of the 79 patients, 70 (89%) had stage II–IV disease and 41 (52%) had radiological pelvic lymph node enlargement. The 5-year disease-specific survival (DSS) rate of the entire cohort was 66.4% (median follow-up 54 months). Fifty-five patients (70%) achieved sufficient (complete or partial) responses to NAC. Among patients with insufficient NAC responses, the 5-year DSS rate of the surgery group (55.6%) was significantly higher than the RT group (20.0%; P = 0.044). However, among patients with sufficient responses to NAC, 5-year DSS rates did not significantly differ between the surgery and RT groups (82.3 vs 78.6%; P = 0.79) even though the RT group had many more unfavorable prognostic factors and received fewer subsequent treatments than the surgery group. Post-NAC survival outcomes among patients with chemo-sensitive cervical SCC who then underwent RT were not inferior to those treated with surgery, and NAC did not detract from the efficacy of subsequent RT. Among selected patients who respond favorably to NAC, RT could be a less invasive substitute for surgery without compromising treatment outcomes.