Histological Type Of Cervical Cancer Research Articles

Squamotransitional Cell Carcinoma of the Uterine Cervix with Ovarian Metastasis and Benign Brenner Tumor: A Case Report

Introduction: Cervical cancer is the fourth most common malignancy in women and the fourth leading cause of death among women. The main histological types of cervical cancer are squamous cell carcinoma—75% of all cases; adenocarcinoma—10–25%; and all other rare variants including adenosquamous carcinoma and neuroendocrine carcinoma. Squamotransitional cervical cancer is an extremely rare and poorly studied subtype of squamous cell carcinoma. Case report: We present a case of a 64-year-old female patient with early-stage squamotransitional carcinoma. A metastasis was observed in the left ovary and the left fallopian tube and a benign Brenner tumor in the right ovary. Discussion: Although it is believed that this cervical cancer subtype shares the same risk factors and prognosis as squamous cell carcinoma, it is more likely to metastasize and recur. It is not unusual for spread to exist within nearby structures like the cervix and adnexa. It is impossible to tell which is the predominant focus from the immunoprofile of the lesions. Practically speaking, the best course of action in these situations is to rule out the presence of a primary tumor in the urinary tract before clarifying the condition of the cervix, uterus, and adnexal tissues. The presence of a Brenner tumor raises the possibility of a connection between the tumor’s differentiation from a cell population and potential urothelial differentiation. Conclusion: Squamotransitional cervical cancer is a rare tumor with a poorly studied clinical behavior. Despite a shortage of information in the literature, it should be regarded as a more aggressive variety of squamous cell carcinoma and, as such, should be treated and followed up more aggressively. This case is the first described with involvement of the cervix, endometrium, and adnexal structures and a concomitant Brenner tumor.

Prognostic models for predicting overall and cancer-specific survival of patients with initially diagnosed metastatic cervical squamous cell carcinoma: A study based on SEER database.

Cervical squamous cell carcinoma (CSCC) is the most common histological type of cervical cancer (CC). And mCSCC is the end stage of CSCC. The aim of this study was to develop prognostic nomograms that provide better predictions for overall survival (OS) and cancer-specific survival (CSS) in mCSCC patients. Data from patients with initially diagnosed mCSCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The nomograms for OS and CSS were constructed based on Cox regression analysis. The validation of the newly established nomograms was evaluated by concordance index (C-index), calibration curves, and decision curve analyses (DCAs). A total of 2198 patients with mCSCC were included and randomly split into training (n = 1539) and validation (n = 659) cohorts in a 7:3 ratio. Multivariate analyses revealed that the prognostic variables significantly related to the OS and CSS were marital status, T stage, brain metastasis, lung metastasis, tumor size, number of positive lymph nodes, chemotherapy, and radiotherapy. The nomograms were constructed based on these factors. The C-index value of the nomograms for predicting OS and CSS was 0.714 and 0.683, respectively. The calibration curves of the nomograms showed good consistency between nomogram prediction and actual survival for both OS and CSS, and the DCAs showed great clinical usefulness of the nomograms. The mCSCC patients were classified into low- and high-risk groups based on the scores from the nomograms. In the validation cohort, mCSCC patients with low-risk had much higher OS and CSS than those with high-risk. We constructed nomograms for predicting the OS and CSS of patients with initially diagnosed mCSCC. Our models had satisfactory predictive performance and could be useful in survival prediction for mCSCC.

Post-chemotherapy response of paclitaxel and carboplatin regimens in advanced stage cervical cancer types of histopathology squamous cell carcinoma and adenocarcinoma

Background: Cervical cancer incidence in South Borneo was placed 10th in Indonesia. South Borneo Department of Health revealed 1,930 patients diagnosed with cervical cancer in 2019. The main therapy for advanced cervical cancer was radiotherapy, chemotherapy, and combination. This study aims to demonstrate that paclitaxel plus carboplatin regimens have a better post-chemotherapy response in patients with advanced cervical cancer squamous cell carcinoma than adenocarcinoma. Methods: This study used an analytical observational method with a cross-sectional approach. The sample size was taken during the period during which this study was conducted from January 2015 to December 2020 and was taken by total sampling and divided into 2 groups consisting of patients with advanced cervical cancer, squamous cell carcinoma, and adenocarcinoma histological types. Data were analyzed using SPSS version 21.0 for Windows. Results: A total of 202 individuals made up the study's sample, including 54 (26.8%) adenocarcinomas, 148 (73.2%) patients with advanced cervical cancer, and patients with various histological kinds of squamous cell carcinoma. About 107 (52.9%) patients provided complete responses, whereas up to 95 (47.1%) patients provided incomplete responses. Conclusion: Squamous cell carcinoma, the histological type of cervical cancer, responds to treatment better than adenocarcinoma.

High mesothelin expression is correlated with non-squamous cell histology and poor survival in cervical cancer: a retrospective study

BackgroundMesothelin (MSLN) is a cell-surface glycoprotein found in various solid tumours. Cancer therapies targeting MSLN have been developed in recent years; however, the available information on MSLN expression in cervical cancer is limited. This study aimed to evaluate MSLN expression in various histological types of cervical cancer and examine its relationship with prognosis.MethodsThis retrospective study included patients with cervical cancer who underwent primary surgery between January 2000 and December 2020 at our institution. MSLN expression was evaluated by immunohistochemistry using clone SP74 and defined as positive if MSLN was expressed at any intensity. High MSLN expression was defined as an intensity of ≥ 2 + in ≥ 30% of tumour cells. The association between MSLN expression and clinicopathological factors was evaluated.ResultsOverall, 123 patients were identified, and 140 tumour samples, including 17 paired primary and metastatic samples, were evaluated. Concerning histological type, 67 patients had squamous cell carcinoma (SCC), whereas 56 had non-SCC. MSLN expression was observed in 98.4% (121/123) of primary tumours. High MSLN expression was observed in 63.4% of samples (78/123), but it differed between the histological types (49.2% for SCC vs. 80.4% for non-SCC, p < 0.001). There was a significant correlation between MSLN expression in primary and metastatic lesions (Rs = 0.557, p = 0.015). In patients with common histological types, overall survival (OS) was shorter in the high MSLN expression group than in the low MSLN expression group (hazard ratio, 3.53; 95% confidence interval, 1.16–15.3, p = 0.03).ConclusionsMSLN was highly expressed in patients with cervical cancer, especially in those with non-SCC. High MSLN expression in the primary lesion was significantly associated with poor OS, and its expression was maintained in metastatic lesions. Our findings indicate that MSLN may be an attractive therapeutic target for cervical cancer.Trial registrationRetrospectivelyregistered. 2014-393.1 June 2015

CXCL10 serves as a potential serum biomarker complementing SCC-Ag for diagnosing cervical squamous cell carcinoma

BackgroundCervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer which is the major cause of death in women worldwide. Although squamous cell carcinoma antigen (SCC-Ag) is widely used to detect CESC, it is not sensitive and specific enough to predict the disease.MethodsWe investigated serum CXC motif chemokine 10 (CXCL10) as potential diagnostic biomarker in detecting CESC in this study. Serum levels of CXCL10 and SCC-Ag were measured by ELISA or automated immunoassay in 345 participants, including 189 patients with different stages of CESC, 75 patients with cervical intraepithelial neoplasia, and 81 healthy individuals. Performances of CXCL10 and SCC-Ag as single biomarkers were analyzed by the ROC curves. The changes of serum levels of CXCL10 and SCC-Ag in 10 longitudinal followed-up CESC patients with partial response (PR) during chemoradiotherapy or chemotherapy were evaluated.ResultsThe two markers showed similar diagnostic capacity in distinguishing both CESC early stage from healthy controls (AUCCXCL10 = 0.740, AUCSCC-Ag = 0.710) and all CESC from healthy controls (AUCCXCL10 = 0.775, AUCSCC-Ag =0.793). Moreover, CXCL10 showed ability in distinguishing cervical intraepithelial neoplasia from healthy control (AUCCXCL10 = 0.727) and cervical cancer SCC-Ag-negative from healthy control. (AUCCXCL10 = 0.739). The combination of CXCL10 and SCC-Ag displayed significant improvement of AUCs than individual SCC-Ag or CXCL10 in the analysis groups (healthy vs all cervical cancer, healthy vs cervical cancer early stage). The AUCs were improved to 0.877 (AUCSCC-Ag = 0.793, P < 0.05) to distinguish healthy controls from all CESC and 0.828(AUCSCC-Ag = 0.710, P < 0.05) to distinguish healthy controls from CESC early stage by the combination of the two markers, respectively. Significant differences of serum CXCL10 levels were found between CESC patients at late tumor stage and CESC patients at early tumor stage (P < 0.01). Serum CXCL10 levels of the CESC patients who had partial response after treatment significantly decreased during treatment (P = 0.013), whose consistent and inconsistent frequency with the response were the same as serum SCC-Ag levels.ConclusionsThe results indicated that CXCL10 is a potential serum biomarker complementing SCC-Ag in prediction of CESC. CXCL10 showed ability in the diagnosis of SCC-Ag negative CESC and the combination of CXCL10 and SCC-Ag inhibited improved performance compared with SCC-Ag alone.

AHNAK2 is a biomarker and a potential therapeutic target of adenocarcinomas.

Adenocarcinoma is the second largest histological type of cervical cancer, second only to cervical squamous cell carcinoma. At present, despite the clinical treatment strategies of cervical adenocarcinoma and cervical squamous cell carcinoma being similar, the outcome and prognosis of cervical adenocarcinoma are significantly poor. Therefore, it is urgent to find specific biomarker and therapeutic target for cervical adenocarcinoma. In this study, we aim to reveal and verify the potential biomarkers and therapeutic targets of cervical adenocarcinoma. Weighted correlation network analysis (WGCNA) reveals the differentially-expressed genes significantly related to the histological characteristics of the two cervical cancer subtypes. We select the genes with the top 20 significance for further investigation. Through microarray and immunohistochemical (IHC) analyses of a variety of tumor tissues, we find that among these 20 genes, AHNAK2 is highly expressed not only in cervical adenocarcinoma, but also in multiple of adenocarcinoma tissues, including esophagus, breast and colon, while not in normal gland tissues. In vitro, AHNAK2 knockdown significantly inhibits cell proliferation and migration of adenocarcinoma cell lines. In vivo, AHNAK2 knockdown significantly inhibits tumor progression and metastasis of various adenocarcinomas. RNA-sequencing and bioinformatics analyses suggest that the inhibitory effect of AHNAK2 knockdown on tumor progression is achieved by regulating DNA replication and upregulating Bim expression. Together, we demonstrate that AHNAK2 is a biomarker and a potential therapeutic target for adenocarcinomas.

Value of non-Gaussian diffusion imaging with a fractional order calculus model combined with conventional MRI for differentiating histological types of cervical cancer

ObjectiveThis study aimed to evaluate the value of a fractional order calculus (FROC) model combined with conventional magnetic resonance imaging (MRI) for differentiating cervical adenocarcinoma (CAC) from squamous cell carcinoma (SCC). MethodsDiffusion-weighted imaging (DWI) with 9 b values (0–2000s/mm2) was carried out in 57 cervical cancer patients. Diffusion coefficient (D), fractional order parameter (β), and microstructural quantity (μ) together with apparent diffusion coefficient (ADC) were calculated and compared between the CAC and SCC groups. Conventional MRI features included T2WI signal intensity (SI), unenhanced-T1WI SI, enhanced-T1WI SI, and ∆T1WI SI, which were also compared between the two groups. Receiver operating characteristic (ROC) analysis was employed to assess the performance of FROC parameters, ADC, and conventional MRI features in differentiating CAC from SCC. Resultsβ was significantly lower in the CAC group than in the SCC group (0.682 ± 0.054 vs. 0.723 ± 0.084, P = 0.035), while D and μ were not significantly different between the two groups (D, P = 0.171; μ, P = 0.127). There was no significant difference in the ADC value between the two groups (P = 0.053). In conventional MRI features, enhanced-T1WI SI was significantly higher in the SCC group than in the CAC group (985.78 ± 130.83 vs. 853.92 ± 149.65, P = 0.002). The area under the curve (AUC) of β, ADC, and enhanced-T1WI SI was 0.700, 0.683, and 0.799, respectively. The combination of β, ADC, and enhanced-T1WI SI revealed optimal diagnostic performance in differentiating CAC from SCC (AUC = 0.930), followed by β + enhanced-T1WI SI (AUC = 0.869), ADC+ enhanced-T1WI SI (AUC = 0.817), and β + ADC (AUC = 0.761). ConclusionThe FROC model can serve as a noninvasive and quantitative imaging technique for differentiating CAC from SCC. β combined with ADC and enhanced-T1WI SI had the highest diagnostic efficiency.

Molecular Differences between Squamous Cell Carcinoma and Adenocarcinoma Cervical Cancer Subtypes: Potential Prognostic Biomarkers.

The most frequently diagnosed histological types of cervical cancer (CC) are squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Clinically, the prognosis of both types is controversial. A molecular profile that distinguishes each histological subtype and predicts the prognosis would be of great benefit to CC patients. Methods: The transcriptome of CC patients from The Cancer Genome Atlas (TCGA) was analyzed using the DESeq2 package to obtain the differentially expressed genes (DEGs) between ADC and SCC. The DEGs were validated on a publicly available Mexican-Mestizo patient transcriptome dataset (GSE56303). The global biological pathways involving the DEGs were obtained using the Webgestalt platform. The associations of the DEGs with Overall Survival (OS) were assessed. Finally, three DEGs were validated by RT-qPCR in an independent cohort of Mexican patients. Results. The molecular profiles of ADC and SCC of the CC patients of the TCGA database and the Mexican-Mestizo cohort (GSE56303) were determined obtaining 1768 and 88 DEGs, respectively. Strikingly, 70 genes were concordant—with similar Log2FoldChange values—in both cohorts. The 70 DEGs were involved in IL-17, JAK/STAT, and Ras signaling. Kaplan-Meier OS analysis from the Mexican-Mestizo cohort showed that higher GABRB2 and TSPAN8 and lower TMEM40 expression were associated with better OS. Similar results were found in an independent Mexican cohort. Conclusions: Molecular differences were detected between the ADC and SCC subtypes; however, further studies are required to define the appropriate prognostic biomarker for each histological type.

Sociodemographic and clinical characteristics of patients with advanced forms of invasive cervical cancer and morphological features of their tumors

Due to the availability of effective primary prevention methods and screening strategies, cervical cancer is one of the pre-ventable malignancies. Death rates from cervical cancer remain high. Moreover, in most cases, the tumor is detected at advanced stages. It creates the problem of finding the reasons for the late primary diagnosis of invasive cervical cancer. The article discusses issues related to the characteristics of the main histological types of cervical cancer from the standpoint of the clinical, morphological and socio-demographic characteristics of the profiles of patients with advanced disease. The current understanding of the factors associated with late primary diagnosis of cervical cancer at advanced stages is highlighted.

Dysregulation of Transcription Factor Networks Unveils Different Pathways in Human Papillomavirus 16-Positive Squamous Cell Carcinoma and Adenocarcinoma of the Uterine Cervix.

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the most common histological types of cervical cancer (CC). The worse prognosis of ADC cases highlights the need for better molecular characterization regarding differences between these CC types. RNA-Seq analysis of seven SCC and three ADC human papillomavirus 16-positive samples and the comparison with public data from non-tumoral human papillomavirus-negative cervical tissue samples revealed pathways exclusive to each histological type, such as the epithelial maintenance in SCC and the maturity-onset diabetes of the young (MODY) pathway in ADC. The transcriptional regulatory network analysis of cervical SCC samples unveiled a set of six transcription factor (TF) genes with the potential to positively regulate long non-coding RNA genes DSG1-AS1, CALML3-AS1, IGFL2-AS1, and TINCR. Additional analysis revealed a set of MODY TFs regulated in the sequence predicted to be repressed by miR-96-5p or miR-28-3p in ADC. These microRNAs were previously described to target LINC02381, which was predicted to be positively regulated by two MODY TFs upregulated in cervical ADC. Therefore, we hypothesize LINC02381 might act by decreasing the levels of miR-96-5p and miR-28-3p, promoting the MODY activation in cervical ADC. The novel TF networks here described should be explored for the development of more efficient diagnostic tools.

RECURRENT POLYP REVEALING A RARE CASE OF CERVICAL RHABDOMYOSARCOMA: ABOUT A CASE AND REVIEW OF THE LITERATURE

Rhabdomyosarcoma of the uterine cervix is one of the rare histological types of cervical cancer, which occurs mainly in girls and women during genital activity. Given the aggressiveness of the disease, therapeutic strategy is based on the combination of the three treatment modalities (surgery -chemotherapy radiation therapy-).We report a case of cervical rhabdomyosarcoma in a 53 year old woman with no particular pathological history. The first sign reported was postmenopausal metrorrhagia with the presence of a cervical polyp. The bistourning of this polyp was in favour of cervical adenosarcoma. The extension workup showed a cervical mass without metastasis. The patient underwent surgery and underwent a hysterectomy without preservation of adnexae with anatomopathologic results that suggested a cervical rhabdomyosarcoma and a candidate for adjuvant chemo-radiotherapy. Rhabdomyosarcoma of the uterine cervix is a rare tumor that develops most often in young girls. It mainly shows locoregional extension. Treatment is based on surgery including conservative treatment as well as radical treatment associated with perioperative chemotherapy. The role of radiation therapy remains poorly defined.

Qualitative and quantitative characteristics of different types of tumor microvessels depending on the histological type of cervical cancer

Purpose of the study.To give a qualitative and quantitative assessment of different types of tumor microvessels depending on the histological type of cervical cancer (CC).Material and methods.The tumor samples from 76 patients with CC stage I–IIA who received the surgical treatment on the first phase were the object of study. The immunohistochemical study was performed using antibodies to CD34 and podoplanin. Statistical analysis of the data was performed using the Statistica 6.0 software.Results.In CC, the following types of tumor microvessels have been identified: normal microvessels, dilated capillaries (DCs) with a normal endothelial lining, DCs with a weak expression of CD34, DCs of contact type, capillaries in the solid component of tumor, the atypical dilated capillaries (ADCs), the structures with partial endothelial lining and the lymphatic capillaries in lymphoid and polymorphic cell infiltrates. It was found that DCs with a mild expression of CD34 (p=0.0005), DCs of contact type (p=0.000005), and capillaries in the solid component of tumor (p=0.006) were correlated with the prognosis in early CC. The detection frequency of this tumor microvessels was lower in more prognostically favorable squamous non-keratinizing CC, while in the prognostically unfavorable squamous cell keratinizing CC and adenocarcinoma of the cervix uteri, the higher DCs values with a mild expression of CD34 (р=0,004 and р=0.005, respectively) and DC of contact type (p=0.02 and p=0.14, respectively) were typical.Conclusion.We consider it is expedient to further study the relationship of different types of tumor microvessels with clinical and morphological characteristics and prognosis of cervical cancer.

Small cell neuroendocrine carcinoma coexisting with adenocarcinoma of the uterine cervix - a rare entity

Squamous cell carcinoma and adenocarcinoma are the most common histological types of cervical cancer. The co-existence of two histological types is rare. Here we report a case of a 65-year-old woman with a complaint of postmenopausal bleeding and a history of foul-smelling discharge per vagina for 8 months. On examination cervix flared up with growth, bled on touch, parametrium was involved and adherent anteriorly with bladder &amp; posteriorly with the rectum. Cervical biopsy revealed small cell carcinoma coexisting with Adenocarcinoma. Later it was confirmed by immunohistochemistry.&#x0D;

Tipos histológicos do câncer do colo do útero associado com a infecção pelo HPV em pacientes atendidas em hospital de referência oncológica no estado do Pará

Avaliar a prevalência dos tipos histológicos do câncer do colo do útero associado a infecção do HPV em pacientes atendidas em um hospital de referência oncológica em um município do estado do Pará. Estudo observacional e retrospectivo do tipo transversal de caráter descritivo, sendo pesquisa documental, baseado no levantamento de dados epidemiológicos secundários extraídos das fichas de tumor, e dos prontuários dos pacientes do Hospital escolhido. Total de 276 casos registrados oficialmente, observou-se a variável faixa etária a maior taxa correspondia ao grupo de 40 a 60 anos (202 registros - 73,18%), sendo o grupo de 60 anos ou mais com 74 casos. No que consiste em relação aos fatores de riscos mais prevalentes em relação ao câncer de colo de útero, observou-se aqueles que possuíam os fatores de risco para câncer de colo de útero com a presença de HPV correspondiam à metade dos casos (com 138 casos – 50,0 %), sendo que aqueles que não possuíam fatores de risco equivaleram a 105 casos (38,0%), sendo aqueles sem informação com 33 casos (12,0%). Conclui-se que há fatores que influenciam o diagnóstico tardio e a negligência de sinais e sintomas preditivos de câncer de colo de útero.

Prevalence and attribution of high-risk HPV in different histological types of cervical cancer

Objective: To investigate the prevalence of high-risk HPV subtypes in different pathological types of cervical cancer, and analyze the attribution of carcinogenic HPV subtypes in different pathological types. Methods: A total of 1 541 patients with cervical cancer were treated between February 2009 and October 2016 in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The median age at diagnosis was 49 years (ranged 20-82 years old). The numbers of patients with cervical cancer from North China, Northeast China, East China, Central China and other regions (including Northwest, Southwest and South China) were 961, 244, 175, 87 and 74 cases, respectively. Pathological types: 1 337 cases of squamous cell carcinoma (SCC), 87 usual adenocarcinoma (ADC), 23 adenosquamous carcinoma (ASC), 20 mucinous carcinoma (MC), 19 clear cell carcinoma (CCC), 12 endometrioid carcinoma (EC), 25 neuroendocrine carcinoma (NEC), 9 serous carcinoma (SC), 5 villous adenocarcinoma (VADC) and 4 minimal deviation adenocarcinoma (MDAC). The prevalence of high-risk HPV in different regions, age groups at diagnosis and pathological types in cervical cancer were analyzed. The attribution of 13 high-risk HPV subtypes in different pathological types of cervical cancer based on proportional attribution method, and the attribution of high-risk HPV subtypes prevented by 9-valent HPV vaccine in SCC and ADC were calculated. Results: (1) The prevalence of high-risk HPV in 1 541 patients with cervical cancer was 86.6% (1 335/1 541). The multiple high-risk HPV infection rate in patients with SCC ≥60 years old (23.0%, 37/161) was significantly higher than those in patients aged 45-59 years old and ≤44 years old [11.4% (85/747) vs 11.7% (50/429), P<0.01], and the high-risk HPV infection rates of patients with cervical cancer in North China, Northeast China, East China, Central China and other regions were respectively 86.8% (834/961), 87.7% (214/244), 83.4% (146/175), 83.9% (73/87) and 91.9% (68/74). SCC (86.8%, 1 337/1 541) and ADC (5.6%, 87/1 541) were the most common pathological types in cervical cancer. The high-risk HPV prevalence of SCC, ADC, ASC, MC, NEC and VADC were 90.1% (1 205/1 337), 74.7% (65/87), 87.0% (20/23), 65.0% (13/20), 72.0% (18/25) and 5/5 respectively. The high-risk HPV infection rates of SC, EC, CCC and MDAC were 4/9, 3/12, 2/19 and 0/4 respectively. (2) According to proportional attribution, HPV 16 (69.5%), HPV 18 (5.6%), HPV 58 (2.2%), HPV 31 (1.9%), HPV 52 (1.4%) and HPV 33 (1.3%) were the six common high-risk HPV subtypes in SCC. While, HPV 18 (44.1%), HPV 16 (20.5%), HPV 52 (2.3%), HPV 58 (1.2%) and HPV 51 (1.2%) were the main carcinogenic subtypes in ADC. The main carcinogenic high-risk HPV subtypes of ASC, NEC and MC were HPV 18 and HPV 16. The total attribution of HPV 16, 18, 31, 33, 45, 52 and 58 prevented by 9-valent HPV vaccine in SCC and ADC were 82.6% and 68.1% respectively; the attribution of HPV 45 in SCC and ADC were only 0.8% and 0. Conclusions: SCC and ADC are the main pathological types in cervical cancer. SCC, ADC, ASC, MC, NEC and VADC are closely related to high-risk HPV infection. HPV 16 is the main carcinogenic genotypes of SCC. HPV 18 maybe play an important role in the pathogenesis of ADC.

Identification of EPHX2 and RMI2 as two novel key genes in cervical squamous cell carcinoma by an integrated bioinformatic analysis.

Cervical cancer is the fourth most common malignancy in women worldwide and cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer. The dysregulation of genes plays a significant role in cancer. In the present study, we screened out differentially expressed genes (DEGs) of CESC in theGSE63514 data set from the Gene Expression Omnibus database. An integrated bioinformatics analysis was used to select hub genes, as well as to investigate their related prognostic signature, functional annotation, methylation mechanism, and candidate molecular drugs. As a result, a total of 1907 DEGs were identified (944 were upregulated and 963 were downregulated). In the protein-protein interaction network, three hub modules and 30 hub genes were identified. And two hub modules and 116 hub genes were screened out from four CESC-related modules by the weighted gene coexpression network analysis. The gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to better understand functions and pathways. Genes with a significant prognostic value were found by prognostic signature analysis. And there were five genes (EPHX2, CHAF1B, KIAA1524, CDC45, and RMI2) identified as significant CESC-associated genes after expression validation and survival analysis. Among them, EPHX2 and RMI2 were noted as two novel key genes for the CESC-associated methylation and expression. In addition, four candidate small molecule drugs for CESC (camptothecin, resveratrol, vorinostat, and trichostatin A) were defined. Further studies are required to explore these significant CESC-associated genes for their potentiality in diagnosis, prognosis, and targeted therapy.

ADAM9 Expression in Uterine Cervical Cancer and Its Associated Factors

Background:Cervical cancer is a preventable disease caused by human papillomaviruses. It is the third most common cancer to occur in women of reproductive age. The ADAM9 protein plays a role in basement membrane degradation and tumour metastasis in certain types of tumour. Thus, it has the potential to become a new targeted therapy. The objective of this study was to investigate ADAM9 expression in cervical cancer and to determine the factors associated with ADAM9-positive expression.Methods:This cross-sectional study was conducted in Hospital Universiti Sains Malaysia (HUSM) Kelantan, Malaysia from December 2010 to December 2012. Histological slides obtained from 95 cervical cancer cases diagnosed and/or treated in HUSM from 2000 to 2010 were analysed. The ADAM9 immunostain was then performed on the paraffin blocks. The statistical data entry and analysis were done using SPSS version 18.0. Multiple logistic regression analysis was performed to determine the factors associated with ADAM9-positive expression. Result:Of the 95 cervical cancer patients included in the study, 72 (75.8%) patients showed positive ADAM9 expression. The mean age of the patients was 53.89 (10.83) years old. Squamous cell carcinoma was the most common type of cervical cancer (n = 67, 70.5%). Factors that showed a statistically significant association with ADAM9-positive expression were tumour size (adjusted odds ratio [adj. OR]: 1.08; 95% confidence interval [CI]: 1.02, 1.13; p = 0.004), distant metastasis (adj. OR: 12.82; 95% CI: 1.91, 86.13; p = 0.009) and the histological type of cervical cancer (i.e. squamous cell carcinoma) (adj. OR: 7.39; 95% CI: 1.42, 38.51; p = 0.017). Conclusion:The ADAM9 immunostain was consistently positive in malignant cells. Thus, ADAM9 expression can be used as a prognostic/therapeutic indicator in aiding clinician decision-making regarding patient treatment (targeted therapy).

Identification of DAPK1 Promoter Hypermethylation as a Biomarker for Intra-Epithelial Lesion and Cervical Cancer: A Meta-Analysis of Published Studies, TCGA, and GEO Datasets.

Background: Promoter hypermethylation in death-associated protein kinase 1 (DAPK1) gene has been long linked to cervical neoplasia, but the established results remained controversial. Here, we performed a meta-analysis to assess the associations of DAPK1 promoter hypermethylation with low-grade intra-epithelial lesion (HSIL), high-grade intra-epithelial lesion (HSIL), cervical cancer (CC), and clinicopathological features of CC.Methods: Published studies with qualitative methylation data were initially searched from PubMed, Web of Science, EMBASE, and China National Knowledge Infrastructure databases (up to March 2018). Then, quantitative methylation datasets, retrieved from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, were pooled to validate the results of published studies.Results: In a meta-analysis of 37 published studies, DAPK1 promoter hypermethylation progressively increased the risk of LSIL by 2.41-fold (P = 0.012), HSIL by 7.62-fold (P < 0.001), and CC by 23.17-fold (P < 0.001). Summary receiver operating characteristic curves suggested a potential diagnostic value of DAPK1 promoter hypermethylation in CC, with a large area-under-the-curve of 0.83, a high specificity of 97%, and a moderate sensitivity of 59%. There were significant impacts of DAPK1 promoter hypermethylation on histological type (odds ratio (OR) = 3.53, P < 0.001) and FIGO stage of CC (OR = 2.15, P = 0.003). Then, a pooled analysis of nine TCGA and GEO datasets, covering 13 CPG sites within DAPK1 promoter, identified eight CC-associated sites, six sites with diagnostic values for CC (pooled specificities: 74–90%; pooled sensitivities: 70–81%), nine loci associated with the histological type of CC, and all 13 loci with down-regulated effects on DAPK1 mRNA expression.Conclusion: The meta-analysis suggests that DAPK1 promoter hypermethylation is significantly associated with the disease severity of cervical neoplasia. DAPK1 methylation detection exhibits a promising ability to discriminate CC from cancer-free controls.

Human papillomavirus subtypes distribution among 2309 cervical cancer patients in West China.

ObjectiveThe prevalence of cervical Human Papillomavirus (HPV) infection in cervical cancer varies greatly worldwide, and HPV prevalence and genotypes in China are limited. The objective is to analyze the prevalence of HPV subtypes in cervical cancer patients in west China as well as the relationships between different histological types of cervical cancer and HPV subtypes.Results2309 cases were included. 90.86% were infected with HPV, and the remaining 9.13% were negative. The most common subtypes were HPV16, HPV18, HPV58, HPV53, and HPV33. HPV16 and HPV18 appeared to be the most prevalent HPV subtypes across all age groups, while the prevalence of the other subtypes varied between age groups. A logistic regression analysis revealed that the occurrence of cervical squamous cell carcinoma and adenocarcinoma was most closely correlated to a persistent infection with HPV16 or HPV18, with P < 0.05.Materials and MethodsThe prevalence of 27 HPV subtypes in 2309 cervical cancer patients who received treatment at our hospital between June 2011 and January 2016 was analyzed based on the results of HPV testing using Liquid suspension chip technology (Luminex 200).ConclusionsHPV16 and HPV18 were the most prevalent HPV subtypes among the cervical cancer patients, followed by HPV58, HPV53, and HPV33. 9.13% of the cases appeared to not be associated with HPV. This suggests that HPV testing without the use of cytology may overlook some special types of cervical cancer that account for approximately 10% of all cervical cancer cases.

Histological Characterization of Invasive Cervical Cancer and Precursor Lesions in Malawian Women Presenting at Queen Elizabeth Central Hospital (QECH): A Cross-Sectional Study

Background: Cervical cancer is part of the huge burden of diseases in developing countries and is the second most common cancer in women worldwide. In Malawi, cervical cancer ranks as the first most frequent cancer in women between 15 and 64 years of age. We aimed at providing data about the distribution of different histological types of cervical cancer and precancerous lesions in patients presenting at Queen Elizabeth Central Hospital (QECH) in Malawi. Methods: A total of 212 patient samples collected from 1st January, 2014 through 31st December, 2014 were included in the study. Tissue Hematoxylin and Eosin staining technique for microscopic histopathological classification of cervical lesions was used. Data was analyzed using IBM SPSS® version 20.0 for windows. The chisquare and Multinomial logistic regression test with a p-value of less than 0.05 was used to indicate statistical significance of the results. Results: Out of 212 cases having precancerous lesions and cervical cancer that were included in the study, cervical lesions comprised 17% (35/212) pre-cancerous lesions, 65% (137/212) cancerous and 18% (39/212) had both pre-cancerous and cervical cancer, making a total of 176 (83%) cancer lesions. The most common cervical lesion was squamous cell carcinoma (SCC) with 72 % (151/212) cases. Conclusion: Invasive SCC was found to be the commonest type of cervical cancer and high grade squamous intraepithelial lesions (HSIL) the commonest pre-cancerous lesion among women