Normal Cervix Research Articles

Transvaginal Real-time Shear Wave Elastography in the Diagnosis of Cervical Disease.

To explore the value of shear wave elastography in the diagnosis of cervical disease. This work was a retrospective analysis of 246 cases of cervical lesions confirmed by transvaginal conventional ultrasound, shear wave elastography, and a cytologic test. The lesions were divided into 2 groups according to the final pathologic results: a malignant cervical group and a benign cervical group. In addition, the normal cervix was set as the control group. The maximum and mean shear wave velocity values ± SD were 5.24 ± 1.11 and 4.91 ± 1.12 m/s for the malignant cervical group, 3.93 ± 0.39 and 3.53 ± 0.52 m/s for the benign cervical group, and 3.27 ± 0.31 and 2.86 ± 0.23 m/s for the normal cervix, respectively. The areas under the receiver operating characteristic curves for the maximum and mean shear wave velocity in the differential diagnosis of a normal cervix and benign cervical tumors were 0.909 and 0.878 (both P < .001), whereas in the differential diagnosis of benign and malignant cervical tumors, they were 0.909 and 0.895 (both P < .001). Shear wave elastography can quantitatively analyze the elastic characteristics of cervical diseases, help differentially diagnose cervical diseases, accurately determine the extent of tumor invasion, and improve effective clinical staging and treatment.

Serum bradykinin levels as a diagnostic marker in cervical cancer with a potential mechanism to promote VEGF expression via BDKRB2.

Bradykinin (BK) is one of the kinin peptides and preferentially binds to bradykinin B2 receptor (BDKRB2). A recent study indicated that BK played an important role in the occurrence and progression of cancer. In this study, we evaluated the serum BK levels in 130 cervical cancer (CC) cases (including 65 cases with pre- and post-surgery paired samples, another 65 cases with only pre-surgery samples), 35 cervical intraepithelial neoplasia (CIN) cases (pre- and post-surgery paired) and 35 control cases. We found that BK was overexpressed in patients with CC compared to patients with CIN and the control group. When combined with squamous cell carcinoma-related antigen (SCCA), the diagnostic efficacy of BK was prominently enhanced. Moreover, we detected the expression level of the BK receptor BDKRB2 in CC, CIN and normal cervical tissues and observed a higher expression in the CC and CIN tissues than in the normal cervix. We then explored the possible mechanisms of action of BK in promoting the progression of CC. When BK was added to the cell culture medium, human umbilical vein endothelial cell (HUVEC) angiogenesis increased and vascular endothelial growth factor (VEGF) expression in CC cell lines was also elevated. The BK antagonist, HOE140, exerted an opposite effect. The knockdown or the overexpression of BDKRB2 in CC cell lines further confirmed its oncogenic role in angiogenesis. Taken together, the findings of this study suggest that BK may be a diagnostic biomarker for CC and may notably improve the diagnostic efficacy when combined with SCCA. BK promotes the progression of CC by upregulating the expression of VEGF via BDKRB2 and subsequently facilitating angiogenesis.

Association of low expression of E-cadherin and β-catenin with the progression of early stage human squamous cervical cancer.

The precise involvement and mechanisms of human papilloma virus type 16 (HPV16) in epithelial-mesenchymal transition (EMT) of cervical intraepithelial neoplasia (CIN) and squamous cervical cancer (SCC) remain unknown. The present study aimed to examine the expression of EMT indicators and their association with HPV16 in CIN and early stage SCC, and their prognostic value in early stage SCC. The expression levels of E-cadherin, N-cadherin, β-catenin, vimentin, and fibronectin were determined by immunohistochemistry in 40 patients with normal uterine cervix, 22 patients with CIN1, 60 patients with CIN2-3, and 86 patients with SCC, stage Ia-IIa, according to the International Federation of Gynecology and Obstetrics. The expression of the epithelial indicators E-cadherin and β-catenin gradually declined, and the mesenchymal indicators N-cadherin, vimentin, and fibronectin increased with progression of the cervical lesions (P<0.05). Patients with SCC with lymph node metastasis, parametrial invasion, negative E-cadherin, and negative β-catenin expression had shorter overall survival (P=0.001, P=0.015, P=0.014, and P=0.043, respectively) and disease-free survival (P=0.002, P=0.021, P=0.025, and P=0.045, respectively) time. Multivariate survival analysis indicated that lymph node metastasis [Hazard ratio (HR)=3.544; P=0.010], parametrial invasion (HR=2.014; P=0.007) and E-cadherin expression (HR=0.163; P<0.001) were independently associated with overall survival, but also with disease-free survival (HR=3.612, P=0.009; HR=1.935, P=0.011; HR=0.168, P<0.001, respectively). In patients with CINs, HPV16 infection was negatively correlated with the expression of E-cadherin, and positively correlated with the expression of N-cadherin, vimentin, and fibronectin. EMT occurs during the progression of CINs to early stage SCC, and is associated with HPV16 infection in CINs. Lymph node metastasis and parametrial invasion are poor prognostic factors for SCC, while positive E-cadherin expression may serve as a protective prognostic factor for SCC.

Innervation of cervical carcinoma is mediated by cancer-derived exosomes

ObjectiveRecently, our laboratory identified sensory innervation within head and neck squamous cell carcinomas (HNSCCs) and subsequently defined a mechanism whereby HNSCCs promote their own innervation via the release of exosomes that stimulate neurite outgrowth. Interestingly, we noted that exosomes from human papillomavirus (HPV)-positive cell lines were more effective at promoting neurite outgrowth than those from HPV-negative cell lines. As nearly all cervical tumors are HPV-positive, we hypothesized that these findings would extend to cervical cancer. MethodsWe use an in vitro assay with PC12 cells to quantify the axonogenic potential of cervical cancer exosomes. PC12 cells are treated with cancer-derived exosomes, stained with the pan-neuronal marker (β-III tubulin) and the number of neurites quantified. To assess innervation in cervical cancer, we immunohistochemically stained cervical cancer patient samples for β-III tubulin and TRPV1 (sensory marker) and compared the staining to normal cervix. ResultsHere, we show the presence of sensory nerves within human cervical tumors. Additionally, we show that exosomes derived from HPV-positive cervical cancer cell lines effectively stimulate neurite outgrowth. ConclusionsThese data identify sensory nerves as components of the cervical cancer microenvironment and suggest that tumor- derived exosomes promote their recruitment.

Effects of hnRNP E1 and both early genes E2 and E6 of HPV16 together with their interactions on cervical carcinogenesis

Objective: To explore the effects of hnRNP E1 and both early genes E2 and E6 of HPV16 as well as their interactions in the progression of cervical carcinogenesis. Methods: Subjects of this study included 56 women with normal cervix (NC), 58 patients with low-grade cervical intraepithelial neoplasm (CINⅠ) and 50 patients with high-grade cervical intraepithelial neoplasm (CINⅡ/Ⅲ) who were all recruited from the 'Cervical Lesions Study Cohort Project' in Jiexiu of Shanxi province from June to September, 2014. Another 40 patients with cervical squamous cell carcinoma (SCC) were from the Shanxi Tumor Hospital during the same period. Information related to cervical lesions were collected, using a structured questionnaire, with cervical tissues and cervical exfoliated cells gathered from all the participants. HPV infection was detected by flow-through hybridization, while the levels of expression on hnRNP E1, HPV16 E2 and E6 protein were measured by Western Blot. Kruskal-Wallis H test, χ(2) test, trend χ(2) test were analyzed by SPSS 22.0 software, while interaction was evaluated by generalized multifactor dimensionality reduction (GMDR). Results: The overall infection rates of HPV16 related to CINⅠ (15.52%, 9/58), CINⅡ/Ⅲ (40.00%, 20/50) and SCC (67.50%, 27/40) groups were all higher than that of the NC group (8.93%, 5/56) and with an increasing trend on the severity of cervical lesions (trend χ(2)=43.613, P<0.001). The levels of expression on hnRNP E1 protein were significantly different in the groups with different cervical lesions (H=9.98, P=0.019), showing a decreasing trend with the severity of cervical lesions (trend χ(2)=9.495, P=0.002). The levels of expression on HPV16 E2 (H=16.20, P=0.001) and HPV16 E6 (H=15.44, P=0.001) were significantly different in groups with different cervical lesions. Results of GMDR showed that the best interaction model in both groups of CINⅡ/Ⅲ and SCC appeared as hnRNP E1 low expression, HPV16 E2 low expression and HPV16 E6 high expression. However, no similar interaction was seen in CINⅠ (P>0.05). Conclusions: Both low expressions of hnRNP E1 and abnormal expression of HPV16 E2 and E6 could increase the risk of high-grade CIN and cervical cancer. It seemed that they might have an important synergistic effect on the progression of cervical cancer.

Three-dimensional turbo-spin-echo amide proton transfer-weighted mri for cervical cancer: A preliminary study.

Amide proton transfer-weighted (APTw) imaging has shown great potential in the diagnosis of cancer, but has yet not been well studied in cervical cancer. To evaluate the image quality and clinical feasibility of APTw MRI for cervical cancer. Prospective. In all, 75 patients with cervical lesions and 49 healthy volunteers. 3.0 T, 3D turbo spin echo (TSE) APTw sequence. Three radiologists, blinded to the clinical data, independently evaluated APTw image quality with a 5-point Likert scale on 64 patients with pathologically confirmed cervical cancer. APT values, calculated based on asymmetry of acquired Z-spectrum with respect to water frequency, using 3D turbo spin echo volume acquisition with B0 correction, were independently measured by two radiologists, twice for each observer, on 52 cervical cancer lesions and 49 normal cervical stroma with a mean region of interest area of 638.6 mm2 and 557.5 mm2 , respectively. Interobserver agreement was evaluated by Kendall's W test. Intra- and interobserver interclass correlation coefficients (ICC) were computed. Student's t-test was used to compare the differences of APT values between cervical cancer and normal cervix; receiver operating characteristic analysis was performed. Most cases revealed good APTw image quality with excellent agreement (Kendall's W = 0.850, P < 0.001). APT values of cervical cancer and normal cervical stroma were 2.745 ± 0.065 and 1.853 ± 0.059, respectively, with a significant difference (P < 0.0001). Intraobserver ICCs were 0.963 and 0.960 for two readers. Interobserver ICC was 0.993. Area under the curve (AUC) for differentiating cervical cancer from normal cervical stroma was 0.927. The feasible threshold value for AUC was determined as 2.221 with sensitivity of 84.62% and specificity of 83.66%. 3D TSE APTw MRI is feasible in cervical cancer. Cervical cancer showed significantly higher APT values than normal cervix. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1318-1325.

Mesenchymal Stromal Cells Derived from Normal Cervix and Cervical Cancer Tumors Increase CD73 Expression in Cervical Cancer Cells Through TGF-β1 Production.

Mesenchymal stromal cells (MSCs) in the tumor microenvironment (TME) participate together with tumor cells to suppress antitumor effector cells through the production of immunosuppressive factors, such as transforming growth factor-beta 1 (TGF-β1). Furthermore, TGF-β1 can induce 5'-nucleotidase (CD73) expression in various cell types; this functional activity is associated with the production of adenosine (Ado), which is an immunosuppressive nucleoside. In this study, we provide evidence that coculture of MSCs derived from cervical tumors (CeCa-MSC) with CeCa tumor cells increases CD73 expression in tumor cells and the capacity of these cells to generate Ado in a MSC ratio-dependent manner. Interestingly, the increase in CD73 in the CeCa cell membrane corresponded to an increase in the TGF-β1 expression level in the tumor cells and the TGF-β1 content in the supernatants of the CeCa/CeCa-MSC cocultures. The addition of anti-hTGF-β neutralizing antibodies strongly reversed CD73 expression in the tumor cells. This phenomenon was not exclusive to CeCa-MSCs; coculture of MSCs derived from the normal cervix with CeCa cells produced similar results. These results suggest that the interaction of MSCs with CeCa tumor cells in the TME may condition higher TGF-β1 production to maintain an immunosuppressive status not only through the activity of this cytokine per se but also through its ability to induce CD73 expression in tumor cells and generate an immunosuppressive microenvironment rich in Ado.

CDK6 3'UTR polymorphisms alter the susceptibility to cervical cancer among Uyghur females.

AimsCyclin dependent kinase 6 (CDK6) plays a crucial role in malignant tumor whereas less is reported in cervical cancer development. The aim of this study was to evaluate the effects of CDK6 3' untranslated region (3'UTR) polymorphisms on cervical cancer susceptibility among Uyghur females.MethodsThe genotypes of the six CDK6 variants (rs8179, rs42032, rs42033, rs42034, rs42035, and rs42038) were identified among 306 cervical cancer cases and 310 healthy controls with the Agena MassARRAY platform. The associations of the candidate single nucleotide polymorphisms (SNPs) with the cervical cancer risk were evaluated under genetic models using conditional logistic regression analysis. Bioinformatics analysis was performed for SNP function prediction with the online databases. The expression differences between tumor tissues and normal cervix samples were also examined by Real‐time PCR.Results CDK6 rs8179 and rs42033 were correlated to the decreased risk of cervical cancer in Uyghurs under the allele model (rs8179 and rs42033: OR = 0.60, 95% CI: 0.37–0.99, p = 0.043) and log‐additive model (rs8179 and rs42033: OR = 0.62, 95% CI: 0.38–1.00, p = 0.047). Rs8179, rs42032, and rs42033 were associated with susceptibility to high‐grade cervical cancer in different genetic models as well (p < 0.05). Dataset‐based analysis also uncovered the potential effects of these significant SNPs. In addition, aberrant expression of CDK6 were detected in cervical tumors.ConclusionsOur results suggested the relationships between CDK6 3'UTR polymorphisms and cervical cancer pathogenesis, and the involvement of CDK6 in cervical cancer development among Uyghur females.

Gestational age-related changes in shear wave speed of the uterine cervix in normal pregnancy at 12-35 weeks' gestation.

Background This study aimed to analyze age-related changes in shear wave speed (SWS) of the normal uterine cervix. Methods We studied 362 women with a normal singleton pregnancy at 12-35 weeks' gestation. The SWS of the cervix was measured using transvaginal ultrasonography at the internal os region of the anterior cervix (IOA), posterior cervix (IOP) and cervical canal (IOC), and at the external os region of the anterior cervix (EOA), posterior cervix (EOP) and cervical canal (EOC). The following parameters were analyzed: (1) time trend of SWS of the individual sampling points, (2) comparison of SWS in the internal cervical region and SWS in the external cervical region, and (3) comparison of SWS between the internal and external cervical regions. Statistical analyses were performed using mixed-effects models. Results The SWS of IOP decreased in bilinear regression, with a critical change in the rate at 22 weeks, whereas the SWS of the remaining points decreased linearly. The estimated values of SWS of IOP at 84, 154 and 251 days were higher than those of IOA and IOC (P<0.001). The estimated values of SWS of IOP at 84 and 154 days were higher than those of EOP (P<0.001). Significant differences between IOP and EOP were shown until 244 days (P<0.05). The estimated value of SWS of IOC at 84 days was higher than that of EOC (P<0.001). Significant differences between IOC and EOC were shown until 210 days (P<0.05). Conclusion The SWS of the uterine cervix in pregnancy decreases with advancing gestation. The SWS of IOP had the highest value among the sampling points with unique characteristics.

Biogenic synthesis, characterization of gold nanoparticles using Lonicera japonica and their anticancer activity on HeLa cells

Metal nanoparticles synthesis using plant extract is one of the most attractive and ecofriendly methods. In the present report, gold nanoparticles (AuNPs) were synthesized using Lonicera japonica flower-extract for in vitro anticancer activity against cervical cancer. The formation of AuNPs were indicated by color changes (light-yellow to ruby-red), and confirmed by UV–vis spectroscopy (absorbance ∼530–580 nm). The synthesized AuNPs size about 10–40 nm with mostly spherical and few triangular, and hexagonal shapes. Elemental composition and crystalline nature were confirmed by EDX and XRD, respectively. FTIR studies revealed the presence of plant materials on the surface of AuNPs, which could be responsible for formation of AuNPs. GC-MS analysis was utilized to determine the phytochemical composition of L. japonica flowers. The synthesized AuNPs were checked for the cytotoxic effect on normal embryonic kidney cells (HEK293) and cervix cancer (HeLa) cells. In conclusion, the normal cells were remaining unharmed while cancer cells growth inhibition was observed dose dependent. From immunofluorescent staining studies of HeLa cells, condensation and fragmentation of nuclear material were observed that indicates apoptotic cell death. These results clearly suggested that eco-friendly synthesis of AuNPs using flower-extract of L. japonica could be used to treat cervical cancer cells.

Vasculogenic Mimicry Formation Is Associated with Erythropoietin Expression but Not with Erythropoietin Receptor Expression in Cervical Squamous Cell Carcinoma.

Background Vasculogenic mimicry (VM), as an endothelium-independent cancer microcirculation, has been observed in many malignancies including cervical cancer. Erythropoietin (EPO) and erythropoietin receptor (EPO-R) could produce an angiogenic effect to promote cervical squamous cell carcinoma (CSCC) progression. However, the association between VM formation and EPO/EPO-R expression in CSCC is poorly explored. Methods Seventy-six paraffin-embedded CSCC samples, 25 high-grade squamous intraepithelial lesion (HSIL) samples, 20 low-grade squamous intraepithelial lesion (LSIL) samples, and 20 normal cervix samples were collected. Immunohistochemistry SP method was performed to detect EPO/EPO-R expression and CD31/periodic acid-Schiff (PAS) double staining was performed to detect VM formation. The associations of EPO/EPO-R and VM with clinicopathological parameters of CSCC were analyzed. The associations between VM formation and EPO/EPO-R expression were also analyzed. Results The positive expression rates of EPO and EPO-R were gradually increasing along the progression of normal cervix-LSIL-HSIL-CSCC sequence (P<0.05). EPO and EPO-R expression were not significantly associated with clinicopathological parameters of CSCC patients (P>0.05). VM was significantly associated with FIGO stage, lymphovascular space involvement, and lymph node metastasis (P<0.05). VM was positively associated with EPO expression (r=0.284, P<0.05) but was not associated with EPO-R expression (P>0.05). Conclusion These data suggest that increased EPO/EPO-R expression may play an important role in cervical carcinogenesis. EPO overexpression may promote VM formation in CSCC.

Relationship between the Cervical Microbiome, HIV Status, and Precancerous Lesions.

Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with high-grade squamous intraepithelial lesions (HSIL) (P = 0.13) than those without lesions. The most abundant OTUs associated with high-grade squamous intraepithelial lesions were Mycoplasmatales, Pseudomonadales, and Staphylococcus We suggest that a chronic mycoplasma infection of the cervix may contribute to HPV-dependent dysplasia by sustained inflammatory signals.IMPORTANCE HPV is known to be the causal agent in the majority of cervical cancers. However, the role of the cervical bacterial microbiome in cervical cancer is not clear. To investigate that possibility, we collected cervical cytobrush samples from 144 Tanzanian women and performed deep sequencing of bacterial 16S rRNA genes. We found that HIV-positive patients had greater bacterial richness (P = 0.01) than HIV-negative patients. We also observed that women with high-grade squamous intraepithelial lesions (HSIL) had greater cervical bacterial diversity than women with cytologically normal cervices. Data from our precise sampling of cervical lesions leads us to propose that Mycoplasma contributes to a cervical microbiome status that promotes HPV-related cervical lesions. These results suggest a greater influence of the bacterial microbiota on the outcome of HPV infection than previously thought.

Contribution of voltage-gated sodium channel \u03b2-subunits to cervical cancer cells metastatic behavior

BackgroundVoltage-gated sodium (NaV) channels are heteromeric proteins consisting of a single pore forming α-subunit associated with one or two auxiliary β-subunits. These channels are classically known for being responsible of action potential generation and propagation in excitable cells; but lately they have been reported as widely expressed and regulated in several human cancer types. We have previously demonstrated the overexpression of NaV1.6 channel in cervical cancer (CeCa) biopsies and primary cultures, and its contribution to cell migration and invasiveness. Here, we investigated the expression of NaV channels β-subunits (NaVβs) in the CeCa cell lines HeLa, SiHa and CaSki, and determined their contribution to cell proliferation, migration and invasiveness.MethodsWe assessed the expression of NaVβs in CeCa cell lines by performing RT-PCR and western blotting experiments. We also evaluated CeCa cell lines proliferation, migration, and invasion by in vitro assays, both in basal conditions and after inducing changes in NaVβs levels by transfecting specific cDNAs or siRNAs. The potential role of NaVβs in modulating the expression of NaV α-subunits in the plasma membrane of CeCa cells was examined by the patch-clamp whole-cell technique. Furthermore, we investigated the role of NaVβ1 on cell cycle in SiHa cells by flow cytometry.ResultsWe found that the four NaVβs are expressed in the three CeCa cell lines, even in the absence of functional NaV α-subunit expression in the plasma membrane. Functional in vitro assays showed differential roles for NaVβ1 and NaVβ4, the latter as a cell invasiveness repressor and the former as a migration abolisher in CeCa cells. In silico analysis of NaVβ4 expression in cervical tissues corroborated the downregulation of this protein expression in CeCa vs normal cervix, supporting the evidence of NaVβ4’s role as a cell invasiveness repressor.ConclusionsOur results contribute to the recent conception about NaVβs as multifunctional proteins involved in cell processes like ion channel regulation, cell adhesion and motility, and even in metastatic cell behaviors. These non-canonical functions of NaVβs are independent of the presence of functional NaV α-subunits in the plasma membrane and might represent a new therapeutic target for the treatment of cervical cancer.

TET1 promotes 5hmC-dependent stemness, and inhibits a 5hmC-independent epithelial-mesenchymal transition, in cervical precancerous lesions

DNA hypermethylation is a driving force in carcinogenesis. However, the role of active DNA hypomethylation in cancer remains largely unknown. This process, facilitated by ten-eleven translocation methylcytosine dioxygenase 1 (TET1), which oxidizes 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5hmC), has never been studied in cervical cancer. Here, we found that TET1 and 5hmC correlative increases from normal cervix to Low-grade squamous intraepithelial lesion (LSIL), maximizing in High-grade squamous intraepithelial lesion (HSIL), and decreasing in invasive cancer. Full-length HPV-immortalized HSIL cells demonstrated higher TET1/5hmC levels, and stemness properties, compared to invasive cancer cells. TET1 silencing promoted the epithelial-mesenchymal transition (EMT), to transform precancerous cells in vivo. TET1 increased 5hmC in the ZEB1 and VIM promoters, surprisingly, silencing both genes. TET1 interaction with the histone modifiers, LSD1 and EZH2, on the ZEB1 promoter, resulted in gene silencing, via loss of histone H3K4 trimethylation, and gain of histone H3K27 trimethylation. Taken together, TET1 promotes stemness properties, and inhibits EMT, in HSIL cells, through 5hmC-dependent and -independent mechanisms.

Promoter hypermethylation of SOX11 promotes the progression of cervical cancer invitro and invivo.

The development of cervical cancer (CC) is a multi‑gene, multi‑step carcinogenic process that involves complex genetic and epigenetic mechanisms. SRY‑related HMG‑box gene11 (SOX11) is a member of the SOX family of transcription factors with an emerging crucial role in the development of various tumor types. To elucidate the function of SOX11 in cervical carcinogenesis, the expression level of SOX11 during the development of human CC was analyzed by immunohistochemistry and western blot analysis. Additionally, the methylation status of the SOX11 was examined using bisulfite sequencing and methylation‑specific polymerase chain reaction. The SOX11 expression and promoter methylation in human CC cell lines were also determined. The effect of SOX11 expression restoration after 5‑aza‑2'‑deoxycytidine (5‑Aza‑dC) treatment on the CC cell proliferation ability was evaluated in CC cell lines. SOX11 was highly expressed in normal cervix (NC) and precancerous low‑grade squamous intraepithelial lesions, but weakly expressed or virtually absent in precancerous high‑grade squamous intraepithelial lesions and CC, which is consistent with the result of the western blot analysis. Hypermethylation of the SOX11 promoter was detected in CC, which was significantly higher than that in NC samples at each CpG site. The expression level of SOX11 in the CC cell lines was downregulated compared with the positive control, Tera‑1human teratoma cell line. Upon 5‑Aza‑dC treatment, SOX11 expression was significantly upregulated in the CC cell lines at the mRNA and protein levels, and cell proliferation was inhibited. The results indicated that the downregulation of SOX11 in CC is due to the hypermethylation of the SOX11 promoter region. Thus, SOX11 methylation may have a role in the growth of CC cells and cervical carcinogenesis.

Prevalence of high-risk human papillomavirus types 16 and 18 among libyan women in tripoli libya

Background and Aims: Despite the well-known association between human papillomavirus (HPV) and cervical cancer, yet there are no available data concerning the prevalence of HPV and its type distribution among Libyan women. The aim of this study was to investigate the prevalence of the most common high-risk HPV types 16 and 18 among Libyan women in Tripoli and to compare it with the cytological findings of the cervix. Methods: A total of 132 cervical samples were collected from women who sought medical attention at the gynecology outpatient clinic of the Tripoli University Hospital and other gynecology private clinics in Tripoli region. Cervical cytological status was classified according to the Bethesda System 2014. Quantitative polymerase chain reaction was used to facilitate the specific detection of HPV types 16 and/or 18. Results: The cytopathological examination showed that 92.4% of women had normal cervical cytology (n = 122/132) and 7.5% (n = 10/132) of them had cervical lesions. The overall prevalence of the most common oncogenic HPV types was 4.5%, as only six samples (n = 6/132) were confirmed of harboring HPV-DNA. Concerning the cytological status of the cervix, HPV-DNA was not found (0%) in women with a normal cervix, and it was present in 60% of women with cervical lesions. The high-risk HPV type 16 was the exclusive type among our all positive samples, with no detection of HPV type 18 among all our recruited subjects. Conclusion: Even though our findings showed a low overall prevalence of high-risk HPV types among Libyan women, the burden of HPV 16 among women with cervical lesions highlights the need to raise attention toward expanding research about HPV and adopt measures to prevent cervical cancer by vaccination and national screening program. The introduction of HPV-DNA testing in cervical cancer management will greatly benefit early-stage HPV detection and help prevent cervical lesions from progression to cancer.

Different expression of GSK3β and pS9GSK3β depending on phenotype of cervical cancer: possible association of GSK3β with squamous cell carcinoma and pS9GSK3β with adenocarcinoma.

ObjectiveThis study aimed to analyze the expression pattern of glycogen synthase kinase 3β (GSK3β) and its phosphorylated forms, GSK3β phosphorylated at Ser9 (pS9GSK3β), and GSK3β phosphorylated at Tyr216 (pY216GSK3β), in cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC).MethodsWe performed immunohistochemical staining for GSK3β, pS9GSK3β, and pY216GSK3β in 64 SCC and 20 AC cases and compared their expression patterns between the 2 tumor types.ResultsIncreased GSK3β and pS9GSK3β expression but decreased pY216GSK3β expression compared with that in the normal cervix were observed in both SCC and AC specimens. Specifically, the levels of GSK3β and pS9GSK3β were significantly increased in SCC and AC, respectively. GSK3β was localized in the nucleus and/or cytoplasm of SCC and AC cells. However, pS9GSK3β was predominantly localized in the membrane of AC cells, whereas it was present in the nucleus and/or cytoplasm of SCC cells.ConclusionThe results suggest that the phosphorylation status of GSK3β changes during cervical cancer development and the different expression levels and patterns of GSK3β and pS9GSK3β are associated with the specific histologic phenotype of cervical cancer.

Association between serum folate level and invasive cervical cancer at a university teaching hospital in South-West Nigeria

Background: Cervical cancer is a common cause of cancer-related morbidity and mortality in developing countries. Serum folate may modify cancer risk through its role in DNA synthesis and methylation. Objective: To determine the association between serum folate levels and the occurrence of cervical cancer among women seen at a university teaching hospital in South-West Nigeria. Patients and Methods: This was an analytical cross-sectional study involving two groups of participants including 50 cases with invasive cervical cancer (ICC) and 50 controls with a normal cervix. Data analysis was performed between discrete baseline characteristics of the cases and controls using the Pearson's Chi-square test, whereas the mean serum folate levels of the cases and controls were compared using the independent sample t-test. P

Molecular Genetic Study to Detect Prevalence of High-risk Human Papilloma Virus Strains (type 16 and 18) in Cervical Lesions and Asymptomatic Healthy Subjects of Rural Central India.

Background:Carcinoma cervix of uterus (CaCx) is the most common malignancy affecting women worldwide. It is an established fact that infection of specific types of human papilloma virus (HPV) is essential for the development of cervical cancer. The present study reports the high-risk viruses (HPV 16 and 18) type distribution in rural central India, which has unique climatic condition. To our knowledge, no molecular study on HPV prevalence has been done in this region of rural population, this intended us do such study.Materials and Methods:Sexually active women reporting to the Gynecology were divided in three groups, first being asymptomatic women with normal cervix (52 cases), second group with benign cervical lesion (52 cases), and third group of women with frank cervical malignancy (40 cases). Cervical swabs were collected for HPV DNA sampling. The incidence of HPV positivity was recorded in each group.Results:Fifty-two women with asymptomatic normal cervix showed 44.23% positivity for HPV 16 and 5.76% positivity for HPV 18. Fifty-two women with benign cervical lesion showed 38.46% positivity for HPV 16 and 3.84% positivity for HPV 18. Forty women with frank cervical malignancy were with prevalence of 62.5% for HPV 16 and 22.5% for HPV 18.Conclusion:The results of the study are definitely helpful to know the prevalence of HPV in this region of rural population and will enrich the national epidemiological data related to HPV infection in cervical cancer.

Expression of epidermal growth factor receptor in squamous cell carcinoma of uterine cervix

Context: Cervical cancer is one of the most important cancer deaths among females. Epidermal growth factor receptor (EGFR) plays a role in cell differentiation, cell motility, neovascularization, invasion, metastasis, and resistance of cancer cells to chemotherapeutic agents and radiation. Tyrosine kinase inhibitors and anti-EGFR monoclonal antibodies have shown better response in various invasive tumors. Aims: The aim of the study is to evaluate EGFR expression in squamous cell carcinoma (SCC) of the cervix and to assess its relation to tumor characteristics. Settings and Design: This was a retrospective, case–control study. Subjects and Methods: Formalin-fixed paraffin-embedded tissues from 30 cases with SCC along with 20 age-matched cases with normal cervix as controls were obtained from the archives. EGFR expression was analyzed in both cases and controls. Statistical Analysis Used: The Chi-square test was used to compare and find the association between the variables. Statistical analysis was done using the IBM SPSS (IBM, Armonk, NY, USA) software and P 4 cm size. There was no association of EGFR expression with tumor grade, tumor stage, and lymph node metastasis. Conclusions: The present study showed that a significantly higher number of cases of invasive SCC of uterine cervix show increased EGFR expression. The EGFR expression is associated with tumor size.