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Emerging evidence indicates that circRNAs play essential roles in tumorigenesis and development. However, the role of circRNAs in cervical cancer (CC) remains unclear. CircRNA microarrays performed on the immortal cervical cell line H8 and the cervical cancer cell line SiHa were used to identify a circRNA, termed circNRIP1 (hsa_circ_0004771), which was upregulated in SiHa. QRT-PCR confirmed that circNRIP1 was upregulated in CC tissues, where its expression was correlated with lymphovascular space invasion. Besides, both in vitro and in vivo experiments demonstrated that circNRIP1 promotes cell proliferation, migration, and invasion. Additionally, we found that miR-629-3p induced tumor suppression by regulating PTP4A1 and the ERK1/2 pathway. Finally, we confirmed that circNRIP1 exerts its effect, at least partially, by sponging miR-629-3p and thereby regulating the PTP4A1/ERK1/2 pathway. Therefore, circNRIP1 may be useful as a potential prognostic biomarker and therapeutic target in CC patients.

The present study aimed to investigate the expression of high-mobility group box 1 protein (HMGB1) in cervical carcinoma and explore whether or not HMGB1 promotes cervical carcinoma cell invasion and migration in vitro and the related mechanism. HMGB1, nuclear factor-κB (NF-κB), E-cadherin and N-cadherin protein expression was analyzed in tissues from 48 cervical carcinomas, 51 cervical intraepithelial neoplasia (CIN) and tissues from 24 healthy controls using immunohistochemistry. HeLa cells were treated with different concentrations of HMGB1 (0, 10, 100, and 1,000 ng/ml) at different time-points (0, 24, 48 and 72 h), and changes in cell morphology and biological behaviors were observed. Changes in the expression levels of E-cadherin, N-cadherin, NF-κB and the inhibitor κB (IκB) in the treated cells were detected by western blot analysis and real-time PCR. HMGB1 expression exhibited a gradually increasing trend in the normal cervical tissues, CIN and cervical cancer, and there was statistical significance between the three groups (P

Wnt-11 is a positive regulator of the Wnt signaling pathway, which plays a crucial role in carcinogenesis. However, Wnt-11 expression in cervical cancer has not been well investigated. The aim of this study was to investigate the role of Wnt-11 in cervical tumor proliferation and invasion. This study examined 24 normal cervical squamous epithelia, 29 cervical intraepithelial neoplasia (CIN), and 78 cervical cancer samples. The expression of Wnt-11 was investigated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction analysis. The expression of the high-risk human papilloma virus (HR-HPV) E6 oncoprotein was also investigated by immunohistochemistry. In addition, the expression of Wnt-11, HR-HPV E6, JNK-1, phosphorylated JNK-1(P-JNK1), and β-catenin was examined by western blot analysis following Wnt-11 knockdown or overexpression in HeLa or SiHa cells, respectively. The promotion of cervical cancer cell proliferation and invasion was investigated using the cell counting kit-8 and Matrigel invasion assay, respectively. Wnt-11 and HR-HPV E6 expression increased in a manner that corresponded with the progression of cervical cancer and was significantly correlated with the International Federation of Gynecology and Obstetrics cancer stage, lymph node metastasis, tumor size, and HPV infection. Wnt-11 protein expression was positively associated with HR-HPV E6 protein expression in all 78 cervical cancer samples (P

Background As part of China's 2009 health-care system reform, a national cervical cancer screening programme was launched, offering free screening by cytology or visuaI inspection with acetic acid and LugoI's iodine (VIA/VILI). We evaluated high-risk HPV (hrHPV) testing as a new screening modality for the national programme. Methods This multicentre, open-label randomised trial was undertaken at nine urban and 11 rural primary-care centres in mainland China. Women aged 35–64 years without history of cervical cancer or hysterectomy, no clinical symptoms of pregnancy, who could understand the study procedures, and voluntarily participated were included. At baseline, women in urban areas were randomly assigned (1:2) to primary screening by cytology or hrHPV, and women in rural areas were randomly assigned (1:1:1) to cytology, hrHPV, or VIA/VILI. Women with baseline hrHPV positive tests were randomly assigned to triage strategies using cytology, VIA/VILI (rural sites), or directly refer to colposcopy. At 24-months, women in urban regions were rescreened with cytology and hrHPV co-testing; rural women received combined hrHPV, cytology, and VIA/VILI screening. Women who showed positive in cytology or VIA/VILI were referred to exams for further colposcopy, and biopsy was then required for participants with abnormal colposcopy results. The primary outcome was cervical intraepithelial neoplasia 2 or worse (CIN2+) and cervical intraepithelial neoplasia 3 or worse (CIN3+). Data analyses were done in the intention-to-screen population (ie, all women assigned to screening). This trial is registered with Chinese Clinical Trial Registry, number ChiCTR1900022530. Findings Between May 18, 2015, and Sept 30, 2016, 61 484 women were assessed as eligible and 60 732 were randomly assigned to screening. Among women in urban regions, 8 955 were assigned to cytology and 18 176 to hrHPV-genotyping; among women in rural regions, 11 136 were assigned to VIA/VILI, 7080 to cytology, and 15 385 to hrHPV-testing. Compared with cytology and VIA/VILI-based primary screening, hrHPV without triaging had 2·0–2·7 times higher baseline CIN2+ or CIN3+ detection (risk ratios: urban hrHPV vs cytology CIN2+ 2·2 [95% CI 1·5–3·1], p Interpretation HrHPV-testing offered better performance than current cytology and VIA/VILI-based primary screening and could be incorporated into China's national programme, but with the longer screening intervals recommended by WHO. Funding National Health Commission of China.

To explore the expression of forkhead/winged helix transcription factor p3(Foxp3) and toll-like receptor 4(TLR4) in cervical cancer and evaluate their clinical significance.Foxp3 and TLR4 protein expression was detected in 105 cervical tissue specimens including cervical cancer, cervical intraepithelial neoplasia (CIN), and healthy control samples using immunohistochemistry. Their relationship with clinicopathologic parameters was also determined.Foxp3 and TLR4 had high levels of expression in cervical cancer cells (91.43 and 82.86%, respectively). Foxp3 levels were significantly associated with FIGO stage (P 0.001) and tumor size (P = 0.034), while TLR4 levels were associated with clinical FIGO stage (P = 0.033) and lymph node metastasis (P = 0.031). Their expression levels were not correlated with age, histologic type, or differentiation (all P 0.05). These findings suggest that Foxp3 and TLR4 may be useful prognostic indicators of cervical carcinoma. In addition, there were significant positive relationships between Foxp3 and TLR4 expression (r = 0.703, P 0.001), which shows a possible link and synergistic role of Foxp3 and TLR4 in promoting the immune escape of cervical cancer.Foxp3 and TLR4 may be useful biomarkers for patient prognosis and cervical cancer prediction and treatment.

ObjectivesDickkopf-1 (DKK-1) is involved in osteoporosis, arthritis, and cancer development and can become a potential therapeutic target of these diseases. The different expression of DKK-1 in different cancers shows that the function of DKK-1 depends on the histological type of the cancer cells and the tissue microenvironment. Because DKK-1 is a secreted protein, we investigated whether it could be found in the serum of patients with cervical cancer.Study designThe expression of DKK-1 was measured by enzyme-linked immunosorbent assay (ELISA) in the serum of 60 healthy women, 60 patients with cervical intraepithelial neoplasia (CIN) and 156 patients with cervical cancer. Detailed treatment information of all 156 patients with cervical cancer and exhaustive follow-up data of 138 patients were collected.ResultsThe levels of serum DKK-1 were significantly increased in patients with cervical cancer (11.90 [SD, 17.28] μg/mL) compared with healthy women (1.48 [SD, 1.86] μg/mL) and patients with CIN (4.77 [SD, 10.24] μg/mL) (p=0.00, p=0.00). The expression of DKK-1 in serum was correlated with lymphatic metastasis and tumor diameter in cervical carcinoma and associated with the prognosis of patients with cervical cancer.ConclusionsDKK-1 detection with ELISA as a biological marker can be used for the detection and diagnosis of cervical carcinoma. DKK-1 in serum is a good predictor of poor prognosis in patients with cervical cancer.

Aim: The aim of this study was to explore the effect of Src-homology-2-domain-containing protein, tyrosine phosphatase 2 (SHP-2) on the proliferation of cervical cancer cells. Material and Methods: A total of 45 patients with cervical cancer (stage I–III), 32 with cervical intraepithelial neoplasia and 20 healthy subjects were consecutively recruited. The levels of SHP-2 and interferon (IFN)-β expression in cervical tissues were characterized by immunohistochemistry and statistically analyzed by logistic regression. Following knockdown of SHP-2 expression by a siRNA or pre-treatment with a specific peptide, the effect of SHP-2 expression in THP-1 cells on the growth and survival of SiHa cells and on IFN-β production was determined by co-culture assays, 3-(4,5)-dimethylthiazol (-z-y 1)-3,5-diphenyltetrazolium bromide, and enzyme immunosorbent assay. Results: The levels of SHP-2 expression in cervical cancer tissues were significantly higher than that in cervical intraepithelial neoplasia and uterine myoma tissues (P

The aim of this study was to determine the expression of B7-H3, B7-H4, Foxp3 and IL-2 in cervical cancer tissues, and evaluate the corresponding clinical significance. The expression of B7-H3, B7-H4, Foxp3 and IL-2 in 108 cervical cancer specimens was detected using immunohistochemistry, and their relationship with clinicopathologic parameters was determined. B7-H3, B7-H4 and Foxp3 had high levels of expression in cervical cancer cells (72.22, 80.56, and 91.56%, respectively). B7-H3 levels were only significantly associated with tumor size (P=0.013), while B7-H4, Foxp3 and IL-2 levels were significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.023, 0.014 and 0.036, respectively) and tumor size (P=0.045, 0.010 and 0.021, respectively). Their expression levels were not correlated with age, histologic type, differentiation and lymph node metastasis (all P>0.05). Cox regression multivariate analysis confirmed that B7-H3 or B7-H4 overexpression was an independent prognostic factor. In addition, there were significant positive relationships between the expression of B7-H3 and B7-H4 with Foxp3 (P

Cyclin D1, with a common G/A polymorphism in rs9344, is an essential regulator of the G1 phase in cell cycles and plays an important role in several tumor types, and the homology of cyclin D1 with human papillomavirus (HPV)-16 E7 brought our attention to CCND1 gene in cervical cancer. A total of 738 native Chinese subjects consist of 327 cases and 411 controls were enrolled in this study. CCND1 genotyping was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and partially verified by sequencing of genomic DNA and cDNA. The transcription of cyclin D1 mRNA isoforms was analyzed by quantitative PCR; expression of protein isoforms by immunohistochemistry and Western blotting. We observed that the AA genotype had decreased risk of developing cervical cancer (odds ratio [OR] = 0.332; 95% confidence interval [CI] = 0.113–0.978; P = 0.045). The two mRNA isoforms were both transcripted from A and G allele. Transcript b decreased in squamous cell carcinoma of the uterine cervix (SCCUC) group (P = 0.004), especially poorly differentiated group (P = 0.004), and in G allele group of normal subjects (P = 0.001). In immunohistochemistry analysis, cyclins D1, D1a, and D1b failed to correlate with cervical cancer (P = 0.808, 0.445, and 0.095). However, cyclin D1b was downregulated in SCCUC group analyzed by Western blotting (P = 0.039). This study indicates that CCND1 rs9344 polymorphisms confer host susceptibility to cervical cancer. A allele possesses a relative protective effect probably through the cyclin D1b's inhibition on HPV carcinogenesis. © 2011 Wiley Periodicals, Inc.

Aim: The expression of Dkk-3, as a number of the Dkk family was different in different cancer. Because Dkk-3 encodes a secreted protein, we investigated whether the Dkk-3 protein is secreted into the sera of patients with gynecological cancer. Material & Methods: The levels of Dkk-3 protein were assessed by enzyme-linked immunosorbent assay in the sera of 104 patients with gynecological cancer: 36 with ovarian, 40 with cervical and 28 with endometrial cancers. Results: The serum levels of Dkk-3 protein in patients with ovarian cancer [25.54 (7.99) pg/mL] was lower than in normal individuals [42.08 (14.89) pg/mL] (P = 0.000). But serum levels of Dkk-3 protein in patients with cervical [166.39 (300.68) pg/mL] (P = 0.013) and endometrial cancers [73.64 (23.36) pg/mL] (P = 0.000) were higher than in normal individuals. The serum levels of Dkk-3 protein were associated with clinical stage in patients with cervical and endometrial cancers. In patients with ovarian cancer, the serum levels of Dkk-3 protein were associated with lymphatic metastasis. In patients with cervical cancer, the serum levels of Dkk-3 protein were associated with tumor diameters. Conclusion: Dkk-3 protein detection using enzyme-linked immunosorbent assay as molecular markers can contribute to detection and diagnosis of gynecological cancer, especially for ovarian cancer and endometrial cancer.

Dickkopf-1 (DKK-1) is a secreted protein involved in embryonic development. Dickkopf-1 is also implicated in osteoporosis, arthritis, and cancer and represents a potential therapeutic target for the treatment of these diseases. Because DKK-1 encodes a secreted protein, we investigated whether the DKK-1 protein is secreted into the sera of patients with gynecological cancer. The levels of DKK-1 protein were assessed by enzyme-linked immunosorbent assay in the sera of 104 patients with gynecological cancer including 36 with ovarian, 40 with cervical, and 28 with endometrial cancers. The serum levels of DKK-1 protein were higher in patients with cervical (314.13 [385.02] pg/mL, P = 0.000) and endometrial (46.95 [21.62] pg/mL, P = 0.000) cancers than in healthy individuals (29.45 [11.86] pg/mL). The serum levels of DKK-1 protein were associated with clinical stage in all patients with gynecological cancer. In patients with cervical cancer, the serum levels of DKK-1 protein were also associated with histological type and lymphatic metastasis. Dickkopf-1 protein detection using enzyme-linked immunosorbent assay as a molecular marker can contribute to the detection and the diagnosis of cervical and endometrial cancers, especially for cervical squamous cell cancer.

Galectin-9 (Gal-9) induces adhesion and aggregation of certain cell types and can be a prognostic factor in the patients with melanoma and breast cancer. We assessed the experiments to resolve whether Gal-9 expression in cervical neoplasm links to malignant potential of cervical squamous cell carcinoma (SCC) cells. Gal-9 expression was examined with immunohistochemical techniques in 23 normal cervical squamous epithelia, 17 cervical intraepithelial neoplasia (CIN), and 38 cervical SCC compared to E-cadherin. CIN was divided into low-grade and high-grade squamous intraepithelial lesions (8 LSIL and 9 HSIL), and SCC was into well-, moderately and poorly differentiated SCC (6 WSCC, 20 MSCC and 12 PSCC). Gal-9 and E-cadherin were evidently detected in normal epithelium and endocervical glands, but those in CIN and SCC were significantly faint. Moreover, both the Gal-9 and E-cadherin expressions in HSIL were significant lower than those in LSIL, suggesting their association with malignant transformation. Unexpectedly, Gal-9 and E-cadherin in WSCC were significantly high compared to those in HSIL. Furthermore, those in SCC were inversely correlated with the grade of differentiation (WSCC >> MSCC >> PSCC), implying the possible involvement of Gal-9 and E-cadherin in the differentiation of SCC. In contrast, they were not different among the FIGO stage. Gal-9 expression was well correlated with E-cadherin expression in CIN and SCC but not in normal cervical epithelia. The present results suggest that decreased Gal-9 expression is inversely associated with malignant potential or differentiation of cervical CIN and SCC as a differentiation biomarker.

Cervical cancer is one of the most frequent gynecological malignancies in women worldwide. MicroRNA-195 (miR-195) was recently found highly expressed in cervical cancer. However, the role of miR-195 in the pathology of cervical cancer remains poorly understood. In this study, we first confirmed the downregulation of miR-195 in primary cervical cancer tissues. For the functional study, we introduced the sequences of miR-195 or miR-195 inhibitor into Hela and SiHa cervical cancer cell lines. Overexpression of miR-195 inhibited the proliferation of both Hela and SiHa cells. In contrast, reducing the endogenous miR-195 level by miR-195 inhibitor promoted the proliferation of cervical cancer cells. Flow cytometric assay showed that overexpression of miR-195 induced G1 phase arrest, whereas miR-195 inhibitor shortened G1 phase of cervical cancer cells. In addition, the suppressive role of miR-195 in cell cycle was also demonstrated by the western blot results of various cell cycle indicators, such as phosphorylated retinoblastoma (p-Rb) and proliferating cell nuclear antigen (PCNA), in the gain and loss of function experiments. Furthermore, Dual-Luciferase Reporter Assay revealed that miR-195 targeted the 3'-untranslated region of cyclin D1a transcript, such as to regulate cyclin D1 expression. In summary, our results suggest that miR-195 acts as a suppressor in the proliferation and cell cycle of cervical cancer cells by directly targeting cyclin D1a mRNA.

The diagnostic accuracy of cervical cancer remains a clinical challenge, and a number of studies have used the serum hybrid capture 2 (HC2) human papillomavirus (HPV) DNA in the diagnosis of cervical cancer. The aim of the present meta-analysis was to determine the overall accuracy of HC2 HPV DNA in the diagnosis of cervical cancer. A systematic review of studies from PubMed, Embase, the Cochrane Library, Web of Science, Ovid, Chinese Biomedical Literature Database-disc, Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang database was conducted, and the data concerning the accuracy of HC2 HPV DNA in the diagnosis of cervical cancer were pooled. The methodological quality of each study was assessed by quality assessment for studies of diagnostic accuracy (QUADAS). Statistical analysis was performed by employing Meta-DiSc (version 1.4) and Stata (version 12.0) software. The overall test performance was summarized using receiver operating characteristic curves. Finally, 12 studies, including 12,492 subjects, met the inclusion criteria and then included in this present meta-analysis. The summary estimates for serum HC2 HPV DNA in the diagnosis of cervical cancer were as follows: sensitivity 0.83 (95 % confidence interval (CI) 0.81-0.85), specificity 0.71 (95 % CI 0.69-0.72), positive likelihood ratio 3.65 (95 % CI 1.77-7.54), negative likelihood ratio 0.32 (95 % CI 0.21-0.48), and diagnostic odds ratio 10.54 (95 % CI 4.95-22.46), and the area under the curve was 0.8922. Our findings suggest that HC2 HPV DNA may improve the accuracy of cervical cancer diagnosis, while the results of HC2 HPV DNA assays should be interpreted in parallel with conventional test results and other clinical findings.

The purpose of the study was to determine the expression patterns of Wnt-11 and squamous cell carcinoma antigen in cervical cancer tissues and to explore their clinical significance and correlation with clinicopathological parameters. The expression of Wnt-11 and squamous cell carcinoma antigen was detected in 127 cervical cancer tissues, 21 cervical intraepithelial neoplasia, as well as in 20 healthy controls by immunohistochemistry, and the relationship of Wnt-11 and squamous cell carcinoma antigen expression with clinicopathological parameters was analyzed. Both Wnt-11 and squamous cell carcinoma antigen were more commonly expressed in cervical cancer than in cervical intraepithelial neoplasia and in normal cervical tissue (respectively; P < 0.05); further, Wnt-11 and squamous cell carcinoma antigen expression in cervical cancer were positively correlated (r = 0.271, P < 0.05). In comparing the expression with clinicopathological parameters of tumor samples, Wnt-11 and squamous cell carcinoma antigen were both associated with FIGO stage, lymph node metastasis, and tumor size (P < 0.05), but not with patient age, pathological type, or differentiation. Increased Wnt-11 protein levels in cervical carcinoma samples were associated with a poor outcome in univariate and multivariate analysis. Wnt-11 and squamous cell carcinoma antigen are related to the malignancy degree and metastasis of cervical cancer, and thus may play a coordinating role in the occurrence and progression of cervical cancer. The study indicated that Wnt-11 may be a useful prognostic indicator for cervical carcinoma.

Objective To describe the distribution of specific types of low-risk (LR) human papillomavirus (HPV) among a general population of northern Chinese women. Methods Between 2007 and 2012, 118 096 women were tested with the HPV Geno-Array Test Kit (HybriBio) at China Medical University’s Shengjing Affiliated Hospital, Shenyang, China. Among these women, 80 418 underwent cervical cytology and colposcopic examination, and 30 961 of these had a cervical biopsy. The prevalence of HPV infection among the women was analyzed according to age, and cytologic and histologic findings. Results CP8304 was the most common type of LR-HPV overall, and was most prevalent in the youngest age group. The overall prevalence of LR-HPV (averaged across all types) was 1.7% in women with normal cytology, 8.8% in those with atypical squamous cells of undetermined significance (ASCUS), 8.0% in those with low-grade squamous intraepithelial lesions (LSIL), and 5.8% in those with high-grade squamous intraepithelial lesions (HSIL). LR-HPV alone, without any high-risk (HR)-HPV, was most common among women with ASCUS and cervical intraepithelial neoplasia (CIN) not otherwise specified (CINNOS) together. Co-infections of LR-HPV and HR-HPV were most common among women with LSIL and CIN1. Conclusion These data will facilitate modeling of the cost-effectiveness of a prophylactic LR-HPV vaccination in China.

To identify new genetic risk factors for cervical cancer, we conducted a genome-wide association study in the Han Chinese population. The initial discovery set included 1,364 individuals with cervical cancer (cases) and 3,028 female controls, and we selected a 'stringently matched samples' subset (829 cases and 990 controls) from the discovery set on the basis of principal component analysis; the follow-up stages included two independent sample sets (1,824 cases and 3,808 controls for follow-up 1 and 2,343 cases and 3,388 controls for follow-up 2). We identified strong evidence of associations between cervical cancer and two new loci: 4q12 (rs13117307, Pcombined, stringently matched=9.69×10(-9), per-allele odds ratio (OR)stringently matched=1.26) and 17q12 (rs8067378, Pcombined, stringently matched=2.00×10(-8), per-allele ORstringently matched=1.18). We additionally replicated an association between HLA-DPB1 and HLA-DPB2 (HLA-DPB1/2) at 6p21.32 and cervical cancer (rs4282438, Pcombined, stringently matched=4.52×10(-27), per-allele ORstringently matched=0.75). Our findings provide new insights into the genetic etiology of cervical cancer.

Background Studies have shown that type-specific persistence of high-risk human papillomavirus (HPV) infection contributed significantly to cervical carcinogenesis. Methods In this population-based study (on 24041 women), we report on the prevalent genotypes of HPVs and the prevalent genotypes of HPV persistent infection in the northeast of China. Results Our results showed that in HPV infected women (45.6% in total), (95% CI, 44.97%–46.23%), 17.35% (95%CI, 16.87%–17.83%) suffered persistent infection. The most common high-risk HPV types in persistent positivity were HPV-16 (18.21%; 95%CI, 17.04%–19.38%), HPV-58 (13.2%; 95%CI, 12.17%–14.23%), HPV-18 (8.66%; 95%CI, 7.81%–9.51%), HPV-52 (7.06%; 95% CI, 6.28%–7.84%) and HPV-33 (6.78%; 95% CI, 6.02%–7.54%). The prevalence of persistent infections with HPV-16,–58, −18, −52 and 33 in cervicitis were lower compared to those in CIN (all P Conclusions we provided extensive results of HPV genotype prevalence and distribution in the northeast of China. HPV genotyping is worthwhile to perform because of its independent prognostic value in cervical cancer

Background While HPV infection is the main cause of cervical cancer, genetic susceptibility to HPV infection is not well understood. Tumor necrosis factor alpha (TNF-alpha), involved in the defense against HPV infection, plays an important role in cervical cancer progression and regression. The aim of this study was to investigate the relationship between the TNF-alpha rs1800629 polymorphism and risk of HPV infection or cervical cancer. Methods Three groups were involved in this study of Chinese women. Group 1 consisted of 285 high risk HPV positive cervical cancer patients, Group 2, 225 high risk HPV positive patients without cervical cancer, and Group 3, 318 HPV negative women with no cervical cancer. Blood samples were obtained from all patients and genotyped by PCR-RLFP. Fifty randomly selected samples were further sequenced. Results The allele and genotype distributions of the TNF-alpha rs1800629 polymorphism were not significantly different between each of the groups (P>0.05). There are no significant relationship between rs1800629 polymorphism and high risk HPV infection (OR = 0.649, 95% CI: 0.253–1.670, P = 0.371), cervical cancer (OR = 0.993, 95% CI: 0.376–2.618, P = 0.988), or cervical cancer with HPV infection (OR = 0.663, 95% CI: 0.250–1.758, P = 0.409). Conclusions We demonstrated that there is no association between TNF rs1800629 polymorphism and the HPV infection, or cervical cancer with HPV infection.

The aim of this study was to investigate the detection rate and methods of micrometastases in early-stage cervical cancer by detecting the expression of high-risk HPV DNA and CK19 in pelvic lymph nodes. A total of 104 lymph nodes with/without pathologically confirmed metastases, from 28 patients with early-stage cervical cancer, were included for detection of high-risk HPV DNA and CK19 expression using in situ hybridization and immunohistochemistry, respectively. The detection rate of high-risk HPV DNA and CK19 in lymph nodes in patients with pathologically-confirmed lymph node metastases was higher compared to that in lymph nodes in patients without pathologically-confirmed lymph node metastases (P

This study investigated the expression and prognostic value of SHP-2 in cervical cancer caused by human papillomavirus (HPV) infection. Forty-five specimens from patients with cervical cancer (stage I-III), 32 specimens from patients with cervical intraepithelial neoplasia (CIN) (I, II) and 20 normal cervical samples from patients with hysteromyoma were collected in Department of Pathology for comparison. The expression levels of SHP-2 and IFN-β proteins were detected by using immunohistochemistry. The mRNA expression level of SHP-2 was detected by using quantitative real-time polymerase chain reaction (PCR). HPVs were detected by HPV GenoArray Test. The Spearman correlation was used to compare the expression level of SHP-2 in HPV infected cervical cancer vs non-HPV infected normal cervix. The level of SHP-2 protein expression in the cancer tissues (88.8%) was significantly higher than in CIN tissues (62.5%) and normal cervixes (45%) (P0.05 and P0.05, respectively). The SHP-2 mRNA levels in the cancer tissues were upregulated as compared with those in the normal cervixes (P0.05). Twenty-one (46.7%) cervical cancers, 25 (78.1%) CINs and 17 (85%) normal cervixes showed IFN-β positive staining in cytoplasm. There was statistically significant difference in the expression rate of IFN-β between cervical cancer and normal cervix (χ (2)=8.378, P0.05) as well as between cervical cancer and CIN (χ (2)=7.695, P0.05). HPV16/18 infections could be found in normal cervixs (15%), CINs (68.7%) and cervical cancers (84.4%). There was a correlation between HPV infection and SHP-2 expression in cervical cancer (r (s)=0.653, P0.05). SHP-2 may be a useful prognostic and diagnostic indicator for HPV infected cervical cancer. In cervical cancers, SHP-2 mRNA and protein overexpression was associated with IFN-β lower-expression.

Instruction: Type-specific persistence of human papillomavirus (HPV) infection can cause invasive cervical cancer. The distribution and prevalence of HPV genotypes depend on the geographic region and on demographic factors. Methods: This study aimed to investigate the prevalence and distribution of HPV genotypes in uterine cervical lesions in Liaoning Province, China. A total of 1444 cervical swabs from patients with cervical cancer (CC, n = 134), cervical intraepithelial neoplasia (CIN) II/III (n = 517), and CIN I (n = 180) were detected for HPV genotypes using the PGMY09/11 primer system and HPV GenoArray test (HybriBio Ltd., Hong Kong). Age-matched samples of 613 women without cervical neoplasia were analyzed as control. Results: The prevalence of HPV was 82.84% in CC, 89.56% in CIN II/III, 70.56% in CIN I, and 44.70% in control. The 5 leading genotypes in CIN II/III were, in descending order of prevalence, HPV types 16 (61.12%), 58 (14.12%), 33 (13.93%), 31 (8.32%), and 52(6.27%); whereas HPV types 16 (73.13%), 18 (7.46%), 58 (3.73%), and 31/33/39 (all were 2.24%) were in CC. Multiple HPV infections comprising 2 to 5 types were found in 17.59% of the patients. Human papillomavirus 16 was the predominant genotype in all categories. The prevalence of both HPV type 16 and single HPV infection increased with the severity of cervical lesions (P = 0.000). Conclusions: The efficacy of the prophylactic vaccine against types 16 and 18 for preventing cervical cancer would be close to 80% in Liaoning Province, China. Human papillomavirus types 16, 18, 58, 33, and 31 may be predominant high-risk factors for CC and its precursors in this region.

Objectives To investigate the prevalence rates of specific human papillomavirus (HPV) types infecting women in Liaoning Province, China. Methods Specimens from 4780 patients with cervical disease and 165 age-matched controls were tested for HPV genotypes using a chip hybridization assay. Results The infection rates were 35.66% for patients with cervicitis, 54.61% for those with ASCUS, 64.14% for those with CIN, 83.76% for those with cervical cancer in situ, and 83.12% for those with invasive cervical cancer. The most common HPV genotype was HPV-16, followed by HPV-58, HPV-52, HPV-33, HPV-53, and HPV-31. There were 1529 single and 731 multiple infections among the 4780 patients. Single infections with high-risk genotypes were associated with various cervical diseases. HPV-16 was present in 399 of the patients with multiple infections. Conclusion Compared with prevalence rates for other populations, the rates of specific HPV types infecting women are different in Liaoning Province of China.

Background The p21 codon 31 single nucleotide polymorphism (SNP), rs1801270, has been linked to cervical cancer but with controversial results. The aims of this study were to investigate the role of p21 SNP-rs1801270 and other untested p21 SNPs in the risk of cervical cancer in a Chinese population. Methods We genotyped five p21 SNPs (rs762623, rs2395655, rs1801270, rs3176352, and rs1059234) using peripheral blood DNA from 393 cervical cancer patients and 434 controls. Results The frequency of the rs1801270 A allele in patients (0.421) was significantly lower than that in controls (0.494, p = 0.003). The frequency of the rs3176352 C allele in cases (0.319) was significantly lower than that in controls (0.417, p < 0.001).The allele frequency of other three p21 SNPs showed not statistically significantly different between patients and controls. The rs1801270 AA genotype was associated with a decreased risk for the development of cervical cancer (OR = 0.583, 95%CI: 0.399 - 0.853, P = 0.005). We observed that the three p21 SNPs (rs1801270, rs3176352, and rs1059234) was in linkage disequilibrium (LD) and thus haplotype analysis was performed. The AGT haplotype (which includes the rs1801270A allele) was the most frequent haplotype among all subjects, and both homozygosity and heterozygosity for the AGT haplotype provided a protective effect from development of cervical cancer. Conclusions We show an association between the p21 SNP rs1801270A allele and a decreased risk for cervical cancer in a population of Chinese women. The AGT haplotype formed by three p21 SNPs in LD (rs1801270, rs3176352 and rs1059234) also provided a protective effect in development of cervical cancer in this population.