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Background To evaluate the prognostic value of the systemic inflammatory score (SIS) in cervical cancer patients.Methods The optimal cutoff values for inflammatory biomarkers were calculated by X-tile software. The prognostic factors were investigated using univariate and multivariate Cox analyses. Time-dependent receiver operating characteristic (time-ROC) analysis and the concordance index (C-index) were used to compare the prognostic impact of factors. Results In total, 264 patients with cervical cancer were included in the study. The optimal cutoff value for lymphocyte-to-monocyte ratio (LMR) was 4.1. In multivariate analysis, FIGO stage, lymphovascular invasion, lymph node metastasis, preoperative serum albumin (Alb), and LMR were independent prognostic factors (PConclusions The preoperative SIS is a simple and useful prognostic factor for postoperative survival in patients with cervical cancer. It might assist in the identification of high-risk patients among patients with the same FIGO stage.

Objective: According to the 2019 American Society for Colposcopy and Cervical Pathology (ASCCP) recommendations, women with a positive high-risk human papillomavirus (HR-HPV) diagnosis and low-grade cervical intraepithelial lesion (LSIL) cytology result should be referred for further colposcopy examination. However, this strategy results in over-treatment in several cases. In this study, we assessed the performance of extended HR-HPV genotyping in women with a simultaneous positive HR-HPV and LSIL diagnosis with the aim of improving the current triage strategy. Methods: This study was an observational analysis of women from the Fujian Province Cervical Lesion Screening Cohorts (FCLSCs). Women who were HR-HPV-positive and had a cytological examination of LSIL, which were followed up with colposcopy and biopsy, from 2015 to 2018 were included. The study endpoint was defined as the detection of histological cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We combined HR-HPV genotypes according to the prevalence rate in histological CIN2+ and ranked them from high to low to establish HR-HPV genotyping models. Outcomes were assessed with respect to sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and colposcopy referral rate. Results: Overall, 56,788 women undergoing preliminary screening for HR-HPV genotyping were included in this study. Among them, 10,499 women positive for HR-HPV underwent a cytology examination, and 902 women with LSIL cytology diagnosed and subsequent biopsy results were included in the final evaluation. Among these patients, 25.1% (226/902) were found to have CIN2+ in histology. HPV-16, -58, -52, -18, -33, and -31 infections were the most common genotypes, and HPV-16, -18, -58, -33, and -31 (odds ratio [OR] = 5.41, 2.98, 1.38, 1.24, and 1.21, respectively) were associated with the potential for histological CIN2+, from the highest to lowest. In the detection of CIN2+ lesions in HR-HPV-positive LSIL women of different HR-HPV genotyping models, the extended HPV 16/18/31/33/52/58 genotyping model was found to have better efficacy with higher sensitivity (92.9%) and NPV (93.0%), but a significantly lower colposcopy referral rate (74.7%) than the ASCCP-recommended HR-HPV non-genotyping model. Conclusion: For HR-HPV-positive women with LSIL, the HPV 16/18/31/33/52/58 genotyping model can serve as an alternative approach to the ASCCP recommendations, potentially reducing the unnecessary colposcopy referral burden in China.

Xiqi Huang,1 Guanyu Ruan,1,2 Guifen Liu,1 Yuqin Gao,1 Pengming Sun1,2 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Provincial Maternity and Children’s Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of ChinaCorrespondence: Pengming SunKey Laboratory of Women and Children’s Critical Diseases Research, Fujian Provincial Maternity and Children’s Health Hospital, Affiliated Hospital of Fujian Medical University, No. 18. Daoshan Road, Gulou District, Fuzhou, 350001 Fujian, People’s Republic of ChinaTel +86 591 8755 8732Fax +86 591 8755 1247Email sunfemy@hotmail.comPurpose: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and estrogen-related receptor alpha (ERRα) play a vital role in various human cancers. The purpose of this study was to investigate whether the PGC-1α/ERRα axis could serve as an effective prognostic marker in ovarian cancer (OC).Patients and Methods: We investigated the expression of both PGC-1α and ERRα in 42 ovarian cancer and 31 noncancerous ovarian samples by immunohistochemistry (IHC). The relationship between the expression of PGC-1α and ERRα in OC and the clinical characteristics of patients was evaluated. In addition, data from the Human Protein Atlas (HPA) database were collected to validate the prognostic significance of PGC-1α and ERRα mRNA expression in OC.Results: PGC-1α and ERRα showed notably higher expression in OC tissues than in noncancerous tissues (P=0.0059, P=0.002). Moreover, in patients with OC, high ERRα and PGC-1α/ERRα expression significantly correlated with tumor differentiation (P=0.027; P=0.04), lymph node status (P=0.023; P=0.021), CA125 (P=0.036; P=0.021), and HE4 (P=0.021; P=0.05), while high PGC-1α expression was only significantly associated with tumor differentiation (P=0.029). The combined analysis of high PGC-1α and ERRα expression revealed a tendency towards poor cancer-specific survival (P=0.1276).Conclusion: PGC-1α and ERRα are overexpressed in OC and might be significant prognostic factors for this cancer.Keywords: prognostic significance, estrogen-related receptor alpha, immunohistochemistry, ovarian malignance, peroxisome proliferator-activated receptor gamma coactivator 1-alpha

Background The diagnosis of postpartum pelvic organ prolapse (POP) relies on symptoms combined with pelvic organ prolapse-quantification (POP-Q) and lacks serological indicators. The objective of this study was to assess serum elastin, type I collagen, miRNA-30d, and miRNA-181a in the early postpartum period to identify hematologic predictors of POP. Material and methods The study included 1013 42- to 60-day-postpartum women who had delivered at Quanzhou Women's and Children's Hospital from October 1, 2016, to October 31, 2017. This study was performed in accordance with the Declaration of Helsinki. The pregnancy and childbirth characteristics and pelvic floor function were evaluated. Forty cases with and without POP were matched, and serum elastin and type I collagen were determined by enzyme-linked immunosorbent assay (ELISA). Reverse-transcription polymerase chain reaction (RT-PCR) was used to detect miRNA-30d and miRNA-181a in 15 pairs. Results Of the 1013 women recruited, 699 (69.00%) were diagnosed with POP. The mean age was 29.00 years old, and the mean body mass index (BMI) was 22.6 kg/m2. In the univariate analysis, age ≥35 years (OR, 1.449; 95% CI, 0.965, 2.298), postpartum BMI ≥ 24 (OR, 4.402; 95% CI, 2.657, 6.148), neonatal weight ≥4 kg (OR, 4.832; 95% CI, 1.373, 17.290) and vaginal delivery (OR, 2.751; 95% CI, 1.855, 4.081) were risk factors for postpartum POP. There were no significant differences in the concentrations of serum elastin and type I collagen between the groups (P=0.52; P=0.26). There were significant differences in the concentrations of miRNA-30d and miRNA-181a between the groups (P=0.004; P=0.003). Conclusion miRNA-30d and miRNA-181a tended to be increased in women with POP and could be potential clinical predictors.

Purpose The aim of this study was to investigate the clinical characteristics and management of malignant ovarian tumors during pregnancy, as well as the feto-maternal outcomes and analyze the influential factors on the pregnancy outcomes. Patients and Methods Eighty-five patients with ovarian malignancies during pregnancy treated at 12 tertiary hospitals between 2009 and 2019 were analyzed in this study. The clinical features, histopathological characteristics, clinical management, and maternal and perinatal outcomes were retrospectively analyzed. The clinical features and managements were compared between abortion group and live birth group. Results The following diagnoses were made: 41 (48.24%) patients with borderline ovarian tumors, 18 (21.18%) patients with epithelial ovarian cancers, 17 (20.00%) patients with non-epithelial ovarian malignancies and 9 (10.59%) patients with metastatic ovarian tumors. Thirty-six (42.45%) patients underwent conservative surgical treatment. Thirty-four (40.00%) patients opted for fertility-sparing surgery, and fifteen (17.56%) patients received radical surgery. Chemotherapy was administered to 32.94% of the patients. The proportion of ovarian malignancies diagnosed in the first trimester in the abortion group was higher than that in the live birth group (P

Purpose Human papillomavirus-16 (HPV-16) is the most carcinogenic HPV genotype. This study aimed to evaluate the clinical value of POU5F1B and HPV-16-E2/E6 by cervical cytology specimens to predict the cervical intraepithelial neoplasia two grade and more (CIN2+). Methods Finally, 248 patients with HPV-16 single infection were enrolled. Using cytology specimen by real-time quantitative PCR (qPCR), POU5F1B mRNA and HPV-16-E2/E6 were detected. The relationship of POU5F1B, HPV-16-E2/E6 and CIN2+ were analyzed, and the optimal cut-off values of POU5F1B and HPV-16-E2/E6 to predict CIN2+ were calculated. Results The mean HPV-16-E2/E6 decreased significantly with cervical lesions development, especially compared with CIN2+ (p

Purpose We investigated the relationship between metabolic syndrome (MetS) and its components and erythrocyte parameters such as red blood cell count (RBC) and hemoglobin (Hb) levels, and their association with the risk of deep myometrial invasion in endometrioid endometrial carcinoma (EEC). Patients and methods A total of 473 women diagnosed with EEC between January 2012 and December 2018 were included in the study. MetS was diagnosed using a modified version of the Chinese Diabetes Society 2004 criteria. Demographic and clinical characteristics were stratified by MetS and compared. Logistic regression analyses were performed to calculate the odds ratios (ORs) of myometrial invasion. Results The prevalence of MetS was 18.8% (89/473). RBC and Hb levels were significantly higher in EEC patients with MetS. RBC and Hb values increased linearly with the number of MetS components. The OR of the MetS risk increased across the RBC quartiles (OR=2.212, 95% confidence interval [Cl]=1.125-4.350, P˂0.05). Among EEC patients with MetS, the OR of deep myometrial invasion increased with the decrease of the RBC quartiles (P=0.037). Similarly, in EEC patients with obesity and hyperglycemia or with ≥2 MetS criteria, the lowest RBC level (Q1) was a risk factor for deep myometrial invasion compared with the reference RBC group (Q4, P˂0.05). However, this trend was not evident in EEC patients without MetS and its components. Conclusion EEC with MetS and its components had higher RBC and Hb levels. The association between the erythrocyte parameters and myometrial invasion differed with MetS. RBC was identified as a risk factor of myometrial invasion in EEC patients with MetS and its components.

Purpose To evaluate the level of human papilloma virus (HPV)-related knowledge and vaccination willingness of people in Fujian Province, and to explore the factors influencing doctors' recommendation of HPV vaccine. Methods We conducted two cross-sectional surveys in Fujian Province. The study cohort included 248 medical staff and medical students and 1001 community members. Descriptive statistics were used to identify the general demographics of the participants, along with their knowledge and attitudes regarding HPV and vaccination. Analyses were conducted to identify factors associated with willingness to vaccinate and willingness to recommend vaccination. Results The level of HPV knowledge in Fujian province was found to be low, but more than 80% of participants would like to accept HPV vaccine. Medical staff had a higher willingness to recommend HPV vaccine than students (OR= 4.696, CI: 2.698-8.175), which may be related to work experience and acceptance of vaccine price but not to knowledge level. Conclusion Knowledge of HPV in our community population appears to be lower than that in other regions in China. We suggest that a lack of knowledge may not be the main factor affecting the willingness to vaccinate, but we still needed to raise the level of knowledge about HPV to prevent misunderstandings. When the level of knowledge is high, education and per capita household income are not important factors influencing the willingness to vaccinate; only acceptance of vaccine prices significantly affects the willingness to vaccinate. Inclusion of the HPV vaccine in the national immunization program could help to alleviate public concerns regarding the vaccine to change present situation.

BackgroundNew screening techniques may affect the optimal approaches for the prevention of cervical cancer. We evaluated the cost-effectiveness and accuracy of alternative screening strategies to provide evidence for cervical cancer screening guidelines in China.MethodsIn total, 32,306 women were enrolled. The current screening with Cervista®high-risk human papillomavirus (HR-HPV) nongenotyping and cytology cotesting (Cervista®cotesting) was compared with PCR-reverse dot blot HR-HPV genotyping and cytology cotesting (PCR-RDB cotesting). All eligible participants were divided into Arm 1, in which both HR-HPV assays were performed, and Arms 2 and 3, in which the PCR-RDB HPV or Cervista®HR-HPV assay, respectively, was performed. Outcome indicators included the cases, sensitivity, negative predictive value (NPV), colposcopy referral rate and cost of identifying cervical intraepithelial neoplasia of grade 2/3 or worse (CIN2+/CIN3+).ResultsAmong the eligible participants, 18.4% were PCR-RDB HR-HPV-positive, while 16.9% were Cervista®HR-HPV-positive, which reflects good agreement (k = 0.73). PCR-RDB cotesting identified more CIN3+ cases than Cervista®cotesting in the first round of screening in Arm 1 (37 vs 32) and Arms 2/3 (252 vs 165). The sensitivity and NPV of PCR-RDB cotesting for identifying CIN3+ in Arm 1 (sensitivity: 94.9% vs 86.5%; NPV: 99.9% vs 99.7%) and Arms 2/3 (sensitivity: 95.1% vs 80.9%; NPV: 99.9% vs 99.6%) were higher than those of Cervista®cotesting, but the cost was similar.ConclusionsThe PCR-RDB HR-HPV genotyping and Cervista®HR-HPV assay results were consistent. PCR-RDB cotesting possesses optimal cost-effectiveness for cervical cancer screening in China, which has the highest number of cases globally but low screening coverage.

Purpose This study aimed to investigate the inflammatory-immune cells in the peripheral blood of women with polycystic ovary syndrome (PCOS) and assessed the potential correlation between inflammatory-immune cells and infertility in PCOS women. Materials and Methods In this case-control study, the profiles of lymphocyte subsets were analyzed by flow cytometry. White blood cells (WBC), neutrophils (Neu), lymphocytes, Ferriman-Gallwey (F-G) score, testosterone, prolactin, follicle-stimulating hormone, luteinizing hormone, fasting blood glucose, and fasting plasma insulin were measured, together with body mass index. Association between inflammatory-immune cells and PCOS was evaluated. Moreover, inflammatory-immune cells of the PCOS women with infertility were evaluated, and the relative operating characteristic (ROC) curve and cutoff values were calculated. Results The number of WBC, Neu, and lymphocytes was higher in PCOS women than controls (P

Background High-grade squamous intraepithelial lesion (HSIL) is a premalignant condition of the cervical cancer. Loop electrosurgical excision procedure (LEEP) and cold-knife conization (CKC) were the most effective treatment. Most studies focused on the recurrence rate, positive margin rate, residual disease rate, secondary hemorrhage or cervical stenosis of these two methods. At present, there are few researches about the post-operative infection comparing LEEP with CKC for treating HSIL. Methods One hundred and fourteen patients diagnosed as HSIL were underwent cold conization (n=43) or LEEP (n=71), according to 1:2 matching approximately and being divided randomly into two groups. The information, including the post-operational inflammatory complications, the leucorrhea abnormalities, the pathogens isolated from cervical secretions and pathological reports, were collected for comparison. Results There was no significant difference between them in bleeding, diameter, depth or volume of tissue between two groups. However, the operation time of the CKC group (24.81±11.09) minutes was longer than that of LEEP group (15.79±9.82) minutes. Seventeen patients of the LEEP group were admitted postoperatively as emergencies for secondary-hemorrhage. But it did not happen in CKC group. During the follow-up period, 28 patients (CKC 8 vs. LEEP 20) were diagnosis as reproductive tract infections. Fourteen patients (CKC 6 vs. LEEP 8) had leucorrhea abnormalities. Eighteen patient (CKC 3 vs. LEEP 15) isolated pathogens from their cervical secretions. There was no significant correlation between leucorrhea abnormality and cervical secretion abnormality. The positive rate of cervical secretion infection in the LEEP group was higher than the CKC group (P

Objective: This study aimed to identify risk factors associated with the presence of positive surgical margins in cervical conization specimens. Methods: This study is a retrospective analysis of data from women who had undergone conization for cervical intraepithelial neoplasia (CIN) from 2012 to 2018 at Fujian Maternity and Child Health Hospital. Factors extracted from the database included age, gravidity, parity, menopausal status, precone Thinprep cytology test, human papillomavirus (HPV) test, precone biopsy, precone endocervical curettage (ECC) result, conization method, operating surgeon, cone dimension, and pathology of the conization specimen, including grade of CIN, margin status and glandular involvement. Univariate and multivariate analyses were performed to identify risk factors associated with positive margins. Results: Data from 495 women were analysed. The proportion of positive margins was 24.85% overall, which varied according to the conization method (27.22% for loop electrosurgical excision procedure vs. 18.52% for cold-knife conization, p = 0.047) and was increased as the severity of the treated lesion increased (10.07% for CIN2 vs. 30.62% for CIN3, p < 0.001). HPV-16 genotype infection, abnormal precone ECC result, higher grade of biopsy, larger cone length and volume, and glandular involvement were significantly associated with positive margins on univariable analysis. After logistic regression analysis, only an abnormal precone ECC result (odds ratio 1.952; 95% confidence interval 1.037–3.676; p = 0.038) remained significant. Conclusions: In the present study, an abnormal precone ECC result was identified as an independent risk factor for positive margins in cervical conization specimens. More aggressive treatment may be considered in patients with abnormal precone ECC results in clinical practice.

Colposcopy is an essential medical examination that mainly through visual inspection for cervical epithelial tissue to preventing cervical cancer. However, screening by artificial vision has the problems of missed diagnosis, low efficiency, and diversity. This paper proposes a deep learning-based method using multi-CNN decision feature integration for classification and diagnosis of cervical lesions. The proposed method first uses the k-means algorithm to aggregate training data into specific classes in data preprocessing and then trained in cross-validation to improve the generalization ability of the model. Subsequently, two kinds of CNN are separately fine-tuned based on the transfer learning, and then XGBoost algorithm is used to integrate the different CNN decision results for optimizing the final prediction. Two integration ways for decision features (named inner-model integration and outer-model integration) are proposed to embody multi-feature integration from the data level and the model structural level. Simultaneously, two specific integration strategies (inner-to-outer and outer-to-inner) are designed for as the final output based on the combination of the two ways. Experimental results show that the K-means data preprocessing method can improve the training of neural networks, and the proposed multi-decision feature fusion strategy can better obtain the results of computer-aided diagnosis that meet the needs of clinical diagnosis.

Purpose: Ovarian cancer is one of the common gynecological malignancies, which is prone to metastasize and thus causes a high fatality rate. Estrogen-related receptor alpha (ERRα) is highly expressed in various malignant tumors. Our objective was to explore the impact of ERRα expression on the progression of ovarian cancer. Methods: The correlation between ERRα expression level and clinical pathological parameters in ovarian cancer tissues were analysed via cancer public database CPTAC. The expression level of ERRα in ovarian cancer cells were confirmed by RT-qPCR and Western Blot methods. The cellular ERRα expression was up-regulated via lentivirus transfection and down-regulated via specific antagonist. The invasion and metastasis capabilities of ovarian cancer cells were observed by wound healing assay and trans-well chamber assay. Results: The CPTAC database showed that the ERRα expression levels were higher in the late-stage and high-grade ovarian cancer tissues compared with those in early-stage and low-grade tissues. Ovarian cancer cells with higher expression level of ERRα had stronger invasion and metastasis capabilities in vitro. After up-regulating the ERRα expression level, the invasion and metastasis capabilities of ovarian cancer cells were enhanced, while down-regulation weakened. Moreover, there was a positive correlation between the percentages of wound closure and cellular ERRα mRNA expression level (r=0.921, PConclusions: Our results suggest that ERRα may play a positive role in the progression of ovarian cancer, and may serve as a promising predictive biomarker.

Background: China’s Fujian Cervical Pilot Project (FCPP) transitioned cervical cancer screening from high-risk human papillomavirus (HR-HPV) nongenotyping to genotyping. We investigated the clinical impact of this introduction, comparing performance indicators between HR-HPV genotyping combined with cytology screening (HR-HPV genotyping period) and the previous HR-HPV nongenotyping combined with cytology screening (HR-HPV nongenotyping period). Methods: A retrospective population-based cohort study was performed using data from the FCPP for China. We obtained data for the HR-HPV nongenotyping period from 1 January 2012 to 31 December 2013, and for the HR-HPV genotyping period from 1 January 2014 to 31 December 2016. Propensity score matching was used to match women from the two periods. Multivariable Cox regression was used to assess factors associated with cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). The primary outcome was the incidence of CIN2+ in women aged ⩾25 years. Performance was assessed and included consistency, reach, effectiveness, adoption, implementation and cost. Results: Compared with HR-HPV nongenotyping period, in the HR-HPV genotyping period, more CIN2+ cases were identified at the initial screening (3.06% versus 2.32%; p Conclusions: Introduction of an HR-HPV genotyping assay in China could detect more CIN2+ lesions at earlier stages and improve programmatic indicators. Evidence suggests that the introduction of HR-HPV genotyping is likely to accelerate the elimination of cervical cancer in China.

AIM Copy number variations (CNVs) are related to the genetic and phenotypic diversity of cancers and identifying genetic alterations could improve treatment strategies. Here, we used The Cancer Genome Atlas (TCGA) to explore associations between estrogen-related receptor alpha (ESRRA) CNVs and histological grade in patients with ovarian cancer (OC). METHODS Gene expression data and clinical information of 620 OC patients were obtained from The Cancer Genome Atlas）TCGA and associations between ESRRA CNVs and clinical characteristics were evaluated. Multivariate logistic regression analyses to obtain odds ratios (ORs) using a 95% confidence interval (CI) were performed, adjusting for race, age, histological grade, and tumor size. RESULTS ESRRA CNVs were associated with histological grade (OR 0.6235 [95% CI, 0.3593-0.8877]; p

Xiaoqi Sun,1 Huifang Lei,2 Xiaoyan Xie,1 Guanyu Ruan,2 Jian An,2 Pengming Sun1,2 1Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, People’s Republic of China; 2Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, People’s Republic of ChinaCorrespondence: Jian An; Pengming Sun Laboratory of Gynecologic OncologyFujian Provincial Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian 350001, People’s Republic of ChinaEmail anjian1994@foxmail.com; sunfemy@hotmail.comBackground: Post-menopausal patients with cervical intraepithelial neoplasia (CIN) have a high rate of residual or recurrent lesions after treatment, and their risk for cervical cancer later in life is higher than the general population. Hence, management for this specific group of post-menopausal patients needs more attention.Objective: The study aimed to identify risk factors associated with the presence of residual disease in hysterectomy specimens in post-menopausal patients with cervical intraepithelial neoplasia grade 3 (CIN 3).Methods: This study was a retrospective analysis of data from post-menopausal women who had undergone hysterectomy following conization for CIN 3 from 2012 to 2018 at Fujian Maternity and Child Health Hospital. Factors extracted from the database included age, parity, Thinprep cytology results, human papillomavirus (HPV) genotype, biopsy results, pre-cone endocervical curettage (ECC) results, conization method, operating surgeon, cone dimension, margin status and glandular involvement. Univariate and multivariate analyses were performed to identify risk factors associated with residual disease in hysterectomy specimens.Results: Analysis of data from 129 women was performed. The proportion of residual disease was 43.41% overall. A higher grade according to colposcopy biopsy, abnormal pre-cone ECC results, the cone method (LEEP vs CKC), a cone volume > 1.57 cm3, and positive margins in conization specimens were found to be significantly associated with residual lesions on univariable analysis. After multivariate analysis, only an abnormal pre-cone ECC result (odds ratio 3.99; 95% confidence interval (CI) 1.41– 11.33; p = 0.009) remained significant.Conclusion: The rate of residual lesions in uterine specimens was high regardless of the cone margin status in post-menopausal women with CIN 3. Risk-based strategies are needed to identify patients who have abnormal pre-cone ECC results, and definitive treatment with hysterectomy should be considered in post-menopausal patients with an elevated risk for residual lesions.Keywords: cervical intraepithelial lesion, menopause, margin status, endocervical curettage

Diling Pan1 ,* Binhua Dong2,3 ,* Hangjing Gao,2 Xiaodan Mao,2,3 Huifeng Xue,4 Pengming Sun2,3 1Department of Pathology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian, People’s Republic of China; 2Department of Gynecology, Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, People’s Republic of China; 3Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, People’s Republic of China; 4Fujian Provincial Cervical Disease Diagnosis and Treatment Health Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pengming SunFujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou 350001, Fujian, People’s Republic of ChinaTel +86-591-87558732Fax +86-591-87551247Email sunfemy@hotmail.comPurpose: Little is known about the performance of extended high-risk human papillomavirus (HR-HPV) genotyping triage of cytology showing atypical squamous cells of undetermined significance (ASC-US). This study aims to evaluate the effectiveness of triage with different HR-HPV genotype models among women with ASC-US.Materials and Methods: In this study, all women who underwent cervical cytology and HR-HPV genotyping were enrolled from 2014 to 2017 in China, and those with cytology showing ASC-US were referred for colposcopy and/or biopsy. The endpoint was histological detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). The outcome indicators were the sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs) and colposcopy referral rates.Results: In all, 56,788 women were enrolled in this study, and 2658 (4.97%) women were reported to have ASC-US; 10.1% (242/2393) of women with ASC-US were identified as having CIN2+. The HR-HPV infection rate was 95.0% among all women with ASC-US who were identified as CIN2+, and the top five genotypes with prevalence and risk of CIN2+ were HPV16 (OR=26.38), HPV58 (OR=7.04), HPV18 (OR=4.44), HPV33 (OR=3.38), HPV31 (OR=2.97) and HPV52 (OR=2.96). The HPV16/18/31/33/52/58 model achieved higher sensitivity [91.3 (87.8– 94.9)], specificity [70.0 (68.1– 72.0)], PPV [25.5 (22.4– 28.2)] and NPV [98.6 (97.3– 98.7)] for the triage of ASC-US patients than the other HR-HPV-type combination models, but the colposcopy referral rate (36.2%) was significantly lower than that of the recommended HR-HPV nongenotyping model (47.6%).Conclusion: This study confirms that the specific HR-HPV genotype HPV16/18/31/33/52/58 is an alternative strategy for ASC-US triage and can effectively reduce the high burden of colposcopy referrals in China.Keywords: human papillomavirus, genotyping, atypical squamous cells of undetermined significance, cervical intraepithelial neoplasia

Gestational trophoblastic disease (GTD) is a group of interrelated but distinct diseases and has a serious impact on the reproductive health of women. To analyze the expression of Nanog in GTD and to evaluate its potential to predict the development of gestational trophoblastic neoplasia (GTN).The study included 41 normal first-trimester placentas matched by gestational age to 53 regressed-hydatidiform-moles (rHMs), 56 malignant-HMs (mHMs) and 17 choriocarcinomas (CCAs) and evaluated the Nanog expression by immunohistochemistry. The chi-square test, ANOVA, Fisher's exact test and logistic regression were performed to assess the Nanog expression and clinical prognostic factors in GTD.Compared to normal placenta levels, the Nanog expression was increased in GTD samples (Nanog is an independent predictor of clinical outcomes. It can also be a reliable predictor for GTN development from GTD.

Qiaoyu Zhang,1,* Binhua Dong,1,* Lihua Chen,1 Tingting Lin,2 Yao Tong,1 Wenyu Lin,1 Haifeng Lin,1 Yuqin Gao,1 Fen Lin,1 Pengming Sun1,3 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China; 3Department of Gynecology, Fujian Provincial Maternity and Children’s Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pengming SunLaboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of ChinaTel +86 591 8755 8732Fax +86 591 8755 1247Email sunfemy@hotmail.comObjective: To assess the clinical value of the PCR-reverse dot blot human papillomavirus genotyping test during follow-up of patients with CIN grade 2 or worse (CIN 2+).Methods: Four hundred patients with CIN 2+ receiving treatment from January 2008 to January 2017 were included in our study. Postoperative follow-up procedures comprised HPV examination and cervical cytology every 3– 6 months for the first 2 years and then followed up every 6– 12 months. A pathology examination was performed when there was a positive funding for HPV 16/18 or an abnormal ThinPrep cytology test (TCT) with or without positive for HR-HPV according to the American Society for Coloscopy and Cervical Pathology (ASCCP) guidelines.Results: The median follow-up period was 27.10± 12.47 months (ranging from 3 to 50 months). During follow-up, 12.00% (48/400) of the women developed residual/recurrent disease. The highest risk in CIN 2+ and CIN 3+ residual/recurrence was HPV-16/-18 (hazard ratio (HR)=12.898, 95% CI= 6.849– 24.289; HR= 20.726, 95% CI= 9.64– 44.562, respectively). Among the different follow-up methods, type-specific (TP) HR-HPV persistent infection showed the highest cumulative incidence risk (CIR) (84.62%, 95% CI=73.29– 95.94) and HR (5.38, 95% CI= 2.596– 11.149) during the 4-year follow-up period. At the CIN 2+ and CIN 3+ endpoints, TP-HPV testing had relatively high sensitivity (84.62%, 95% CI=73.29– 95.94 and 89.28%, 95% CI= 77.83– 100.00, respectively) and specificity (78.07%, 95% CI= 72.70– 83.44 and 75.73%, 95% CI= 70.30– 81.17, respectively). However, at the CIN 2+/CIN 3+ endpoint, TCT follow-up had a sensitivity of 60.42%/62.16% (95% CI=46.58– 72.25/46.54– 77.79) and specificity of 90.18%/88.72% (95% CI=86.95– 93.41/85.35– 92.10).Conclusion: TP HR-HPV follow-up can provide a reliable and sensitive clinical reference for CIN 2+ postoperative patients.Keywords: papillomavirus, genotype, cell biology, histology, postoperative

The relationship between high-risk-human-papillomavirus (HR-HPV) viral loads and residual/recurrence lesion is uncertain. This study aimed to evaluate the clinical value of HR-HPV viral loads to predict the residual/recurrence lesions among women with high-grade squamous lesions or worse (≥ HSIL) after surgery. Finally, 301 women who underwent primary screening of cervical cancer using polymerase-chain-reaction-(PCR)-reverse-dot-blot-(RDB) human papillomavirus (HPV) genotyping and cytology assays were enrolled. They received surgery and took HR-HPV viral loads with a BioPerfectus Multiplex Real-Time PCR assay. Colposcopy biopsies were performed in patients with HPV-16/18(+) and/or TCT ≥ ASCUS with HR-HPV(+). The risk of HR-HPV viral loads and potentials factors for residual/recurrence lesions were analyzed and the optimal cut-off values of HR-HPV viral loads were calculated. The significant differences were found in residual/recurrence lesions among patients with different ages, margin status, cytology and HR-HPV at 6 months (all P

Background: Recently, the emergency of a novel pneumonia, termed COVID-19, which is caused by a novel beta coronavirus, SARS-CoV-2, has rapidly spread all over

Purpose. This study investigated the infection status and relationship between other common lower genital tract infectious pathogens and high-risk human papillomavirus (HR-HPV) in the high-grade cervical lesions. Methods. Overall, 882 patients were enrolled in this retrospective study, of which 339 patients (≥HSIL group) were confirmed with high-grade squamous intraepithelial lesions (HSIL) or cervical squamous cell carcinoma (SCC), while 543 patients (≤LSIL group) were diagnosed with low-grade squamous intraepithelial lesions (LSIL) or normal cervical pathology diagnosis. Cervical swab specimens were tested for HPV, pathogenic bacteria (PB), U. urealyticum (UU), M. hominis (MH), and C. trachomatis (CT) in both groups. Results. The infection rates of HR-HPV, PB, UU (at high density), and CT were higher in the ≥HSIL group than in the ≤LSIL group (P<0.001); however, higher infection rates with MH were not observed (P>0.05). PB, UU, and CT were associated with HR-HPV infection (P<0.001). The PB and UU infection rates in the ≥HSIL group were significantly different from those in the ≤LSIL group, regardless of whether there was an HR-HPV infection at the same time (P<0.05). However, this was not the case for the CT (P>0.05). Furthermore, 259 pathogenic bacterial strains were detected in 882 cases. The difference in the distribution of pathogenic bacterial flora in the different grades of cervical lesions had no statistical significance, which was prioritized over Escherichia coli (P>0.05). Conclusion. PB, UU, and CT infection is associated with susceptibility to HR-HPV, HR-HPV coinfection with these pathogens might increase the risk of high-grade cervical lesions, and PB and UU might be independent risk factors for cervical lesions.

Purpose To estimate the high-risk human papillomavirus (HR-HPV) prevalence in a hospital-based population using the Cervista® and to determine the clinical value and significance of Cervista for cervical cancer screening in Fujian Province, China. Patients and methods In a hospital-based population, a total of 10,771 women from the Fujian Province were screened for cervical cancer and precancerous lesions using the thinprep cytologic test (TCT) and/or the Cervista. Women with HR-HPV infection and/or abnormal TCT were referred for colposcopy and biopsy. Pathological diagnosis was used as the gold standard. Results The overall HR-HPV prevalence was 16.57%. Among 10,229 cases, 976 had abnormal cytology results, of which, the HR-HPV positivity rate was 60.35% in this opportunistic screening population. The most common HR-HPV infection style was a simple infection. The most common species was A9 which was also the most prevalent species in all age. The women with CIN2+ (high-grade squamous intraepithelial lesion [HSIL]), especially cancer, were mostly concentrated in the age from 51 to 60 years old. The peak of CIN1 (low-grade squamous intraepithelial lesion, LSIL) prevalence was in the women aged 31-40. When using CIN1+, CIN2+ and CIN3+ as observed endpoints, the sensitivities were 86.07%, 92.73%, and 93.30% and negative likelihood ratio (NPV) were 99.15%, 99.75% and 99.83%, respectively. Cervista and TCT co-testing achieved the highest sensitivity and the lowest NLR. Conclusion The Cervista could be easily introduced in clinical practice in combination with TCT for cervical cancer screening in China. Patients with species A9 infection require a more actively clinical intervention.

Binhua Dong,1,* Pengming Sun,1,2,* Guanyu Ruan,1 Weiyi Huang,1 Xiaodan Mao,1 Yafang Kang,1 Diling Pan,3 Fen Lin1 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian, P.R. China; 2Department of Gynecology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian, P.R. China; 3Department of Pathology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian, P.R. China *These authors contributed equally to this work Purpose: Currently, the associations between type-specific high-risk human papillomavirus (HR-HPV) viral loads and cervical lesions are still inconsistent. We aimed to assess the type-specific HR-HPV viral load as a risk triage indicator for development of high-grade squamous intraepithelial lesion or worse (≥HSIL).Patients and methods: A total of 19,446 women who underwent primary screening for cervical cancer using Cervista® HR-HPV and cytology assays were enrolled. The viral loads of 1,396 HR-HPV-positive specimens confirmed by Cervista® assay were detected by BioPerfectus Multiplex Real-Time PCR assay. The correlation between viral loads and cervical lesions was analyzed. The optimal cutoffs of individual HR-HPV viral loads used to predict ≥HSIL were determined from the receiver operating characteristic curve. A logistic regression model was used to analyze the relationship between covariates and the probability of ≥HSIL.Results: The viral loads of HPV-16, -31, -33, -52, and -58 were positively correlated with the severity of the cervical lesion, which was significantly elevated in patients with ≥HSIL, whereas those of HPV-18, -45, -56, -59, and other types were not. The optimal cutoffs of the log10-transformed viral loads for HPV-16, -31, -33, -52, and -58 in identifying ≥HSIL were 4.26, 4.46, 4.48, 4.36, and 4.26 copies per 10,000 cells, respectively. Furthermore, multivariate analysis indicated that type-specific viral loads of HPV-16, -31, -33, -52, and -58 exceeding the cutoffs could be independent risk factors for the incidence of ≥HSIL.Conclusion: The BioPerfectus Multiplex Real-Time PCR viral load assay provides viable triage for ≥HSIL when using appropriate cutoff levels. Keywords: high risk, human papillomavirus, viral load, high-grade squamous intraepithelial lesion, BioPerfectus Multiplex Real-Time PCR

To establish a model for predicting revised American Society of Reproductive Medicine (rASRM) scores before endometrioma surgery based on serum anti-Müllerian hormone (AMH) level and to identify factors that might reliably predict postoperative fertility of women diagnosed with endometrioma.The study population was composed of 134 women with endometrioma, 58 with benign cyst, and 115 with non-ovarian lesion. Preoperative serum AMH level and clinical parameters were compared among three groups. Univariate correlation analyses and multivariate linear regression modeling with a stepwise method were performed for constructing an rASRM scores prediction model. Cox regression analysis was then used to identify predictive variables of spontaneous pregnancy following surgical treatment of endometrioma.Preoperative AMH level were significantly lower in the endometrioma group than in the other two groups (p 0.001). Multivariate linear regression analysis revealed that age (β=-0.324, p 0.001), rASRM scores (β=-0.298, p 0.001) and serum CA125 level (β=-0.176, p = 0.026) independently and negatively correlated with serum AMH level. Cox regression analysis of women with endometrioma who underwent surgical resection indicated that older age (per five-year increase, HR: 0.517; 95% CI, 0.299-0.896) and higher serum AMH level (cut-off value:3.68 ng/ml, HR: 2.383; 95% CI, 1.093-5.197) were independent predictors for postoperative fertility.Patients with advanced staged endometriosis tended to have a lower serum AMH level while postoperative infertility was more likely to occur in older patients with a lower level of serum AMH. Thus, timely detection of AMH levels to assess the severity of ovarian endometriosis and possibility for postoperative pregnancy success is necessary to ensure that optimal medical treatment can be provided.

Objective To evaluate the polymerase chain reaction (PCR)-reverse-dot-blot (RDB) human papillomavirus (HPV) genotyping test as a feasible assay for the cervical cancer primary screening. Methods In a hospital-based cohort, a total of 21,568 women were voluntarily enrolled from March 2009 to November 2016 for evaluating the 3 current cervical cancer screening strategies: co-test, cytology primary and high-risk HPV (HR-HPV) primary by using PCR-RDB HPV genotyping and liquid-based cytology (thinprep cytologic test [TCT]). Women with HR-HPV infection and/or abnormal cytology were referred for colposcopy, and the biopsy or conization was performed according to the American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines. Results Overall, 18.20% (3,935/21,568) of the women were detected as HR-HPV-positive, 5.04% (1,088/21,568) were diagnosed with cervical intraepithelial neoplasia 2 or higher (CIN2+), and 3.43% (739/21,568) with CIN3+. The cumulative incidence rates for CIN2+/CIN3+ in patients with HPV-16/18-positive were 48.28%/37.20%, while they were 0.86%/0.38%, 0.30%/0.15% and 0.18%/0.09% in cytology-negative, HR-HPV-negative and co-test-negative population, respectively. Using CIN2+ and CIN3+ as the observed endpoints, the sensitivity and negative predictive value (NPV) of HR-HPV genotyping as a primary screening tool were 90.99%/99.49% and 91.57%/99.80%. Moreover, using HR-HPV genotyping primary screening could detect the same more CIN2+/CIN3+ cases in baseline-detection as co-testing (990/700 vs. 991/701) and far more than cytology primary screening (903/656, p

Aggressive angiomyxoma is an interstitial tumour that is often misdiagnosed and is likely to recur. There have been few reported cases of angiomyxoma in pregnant women. We report a case of a woman who was previously diagnosed with a tumour in her vulva that increased in size during both of her pregnancies and spontaneously decreased postpartum. Local excision was performed and a gonadotropin-releasing hormone agonist was administered. According to a literature review, aggressive angiomyxoma is associated with good maternal and child outcomes. Caesarean section is not the delivery method of choice, but it is indicated if the tumour is preventing vaginal birth. Treatment for angiomyxoma is mainly postpartum local resection supplemented by hormone therapy. This tumour frequently recurs and patients should undergo long-term follow-up.

Colposcopy is one of the important steps in the clinical screening of cervical intraepithelial neoplasia (CIN) and early cervical cancer. It directly affects the patient's diagnosis and treatment program. Therefore, it is widely used for cervical cancer screening. The present work proposes a cervical lesion detection net (CLDNet) model based on the deep convolutional neural network (CNN). The Squeeze-Excitation convolutional neural network (SE-CNN) employed to extract depth features of the whole image. SE module for feature recalibration. Moreover, the region proposal network (RPN) generated a proposal box of the region of interest (ROI). Finally, the region of interest classified and proposal box regression performed to locate the cervical lesion region. The Squeeze-Excitation (SE block) strengthened important features and suppress non-primary features, improve feature extraction ability, which is beneficial to feature classification and proposal box regression in the regions of interest. It is found that the average precision of the model extraction lesion region is 92.53 % and the average recall rate is 85.56 %, which can play a good role in the auxiliary diagnosis.

Few studies have examined the potential transcription factor (TF) simultaneously associated with cisplatin resistance and metastasis in ovarian cancer. To assess a related mechanism, a 345-channel protein/DNA array and transcriptional activity ELISA were performed to compare the TF activities in the cisplatin-sensitive SKOV3 and cisplatin-resistant SKOV3-DDP cells and in HO-8910 and the homologous highly metastatic HO-8910PM cells. In SKOV3-DDP vs. SKOV3 cells, 43 TFs were up-regulated, while 31 were down-regulated. In HO-8910PM vs. HO-8910 cells, 13 TFs were up-regulated, while 18 were down-regulated. In these two models, 4 TFs (HOXD8(1), HOXD8(2), RB, RFX1/2/3) were simultaneously up-regulated, and 9 TFs (SRE, FKHR, Angiotensinogen ANG-IRE, Pax2, CD28RC/NF-IL2B, HLF, CPE, CBFB and c-Ets-1) were down-regulated. HOXD8 mRNA and protein expression levels measured by reverse transcription polymerase chain reaction and ELISA, respectively, were significantly higher in SKOV3-DDP and HO-8910PM than in their corresponding cell lines (both p p = 0.018, p = 0.001) or benign tumours (p = 0.001, p HOXD8 is potentially associated with both cisplatin resistance and metastasis in advanced ovarian cancer.

Guanyu Ruan,1,* Yiyi Song,2,* Binhua Dong,1 Xiaodan Mao,1 Fen Lin,1 Yafang Kang,1 Shuxia Xu,3 Xianjing Chen,2 Qibin Wu,2 Pengming Sun1,2 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China; 2Department of Gynecology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China; 3Department of Pathology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China *These authors have contributed equally to this work Objectives: The Cervista® high-risk human papillomavirus (HR-HPV) test was evaluated as a primary screening method for cervical cancer in women aged ≥21 years and was compared with different screening and triage combinations.Materials and methods: A nested case–control study within the Fujian provincial Cervical Lesion Screening Cohorts was used to evaluate the Cervista test as the primary cervical screening method in a hospital-based population. Strategy 1 primarily screened using a cytology screen with HR-HPV testing used for triage. Strategy 2 primarily screened using cytology and HR-HPV co-testing. Strategy 3 primarily screened using HR-HPV testing and triaged HPV-positive women based on cytology. Strategy 4 primarily screened using HR-HPV testing and referred A9 pool HPV-positive women to colposcopy directly, whereas non-A9 HPV-positive women were triaged using cytology.Results: There were 10,183 women included in this study; 16.49% (1677/10,183) were HR-HPV‑positive, 9.52% had abnormal cytology, and 9907 women were normal during follow-up. A total of 276 women were diagnosed with cervical intraepithelial neoplasia 2 or worse (CIN2+), 197 with CIN3 or worse (CIN3+), and 70 with cervical cancer. Moreover, 10.15% (20/197) women who were CIN3+ were identified as cytology-negative, while 8.63% (17/197) were HR-HPV negative (P>0.05). The cumulative risk rate for HPV–/cytology– was 0.836 (95% CI,0.424–1.648) in CIN3+ cases. Strategy 4 yielded the highest sensitivity for CIN2+ or CIN3+and the lowest positive predictive value for CIN2+ or CIN3+ among the four screening strategies.Conclusion: The Cervista HR-HPV test can provide a reliable and sensitive clinical reference for the cervical cancer primary screen. Keywords: human papillomavirus, primary screen, A9 pool, liquid-based cytology, histology

Guanyu Ruan,1,* Lixiang Ye,2,* Guifen Liu,3 Jian An,3 Jalid Sehouli,4 Pengming Sun1,3 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, 2Fujian Center for Safety Evaluation of New Drugs, Fujian Medical University, 3Department of Gynecology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Gynecologic Oncology and Gynecology, Charité Campus Virchow-Klinikum, European Competence Center for Ovarian Cancer, University of Berlin, Berlin, Germany *These authors contributed equally tothis work Abstract: The impact of bevacizumab (an anti-vascular endothelial growth factor therapy) remains uncertain, which has been the focus of studies on the management of epithelial ovarian cancer (EOC). To investigate the efficacy of bevacizumab combinations with different regimens in the treatment of patients with EOC, a meta-analysis of Phase III randomized controlled trials was conducted. The databases searched included PubMed, Embase, ClinicalTrials.gov, Chinese Knowledge Infrastructure, as well as the Cochrane Central Register of Controlled Trials. After evaluation of quality, a meta-analysis of valid extracted data was performed using Review Manager (RevMan) software. Five studies with 4,369 patients were included. Bevacizumab plus chemotherapy improved progression-free survival (hazard ratio [HR] =0.63; 95% confidence interval [CI], 0.51–0.77; P0.05) in overall survival. The combination of bevacizumab and paclitaxel plus carboplatin-based regimens offers a new treatment option for women with EOC, especially in those with a high risk of progression. Keywords: epithelial ovarian cancer, bevacizumab, overall survival, chemotherapy, meta-analysis, systematic review

OBJECTIVE To determine the clinical significance of the polymerase chain reaction (PCR)-reverse dot blot (RDB) human papillomavirus (HPV) genotyping assay in cervical cancer screening. METHODS A total of 10,442 women attending the Fujian Provincial Maternity and Children's Health Hospital were evaluated using the liquid-based cytology (thinprep cytologic test [TCT]) and the PCR-RDB HPV test. Women with HPV infection and/or abnormal cytology were referred for colposcopy and biopsy. For HPV DNA sequencing, 120 specimens were randomly selected. Pathological diagnosis was used as the gold standard. RESULTS Using the PCR-RDB HPV test, overall HPV prevalence was 20.57% (2,148/10,442) and that of high-risk (HR)-HPV infection was 18.68% (1,951/10,442). There was 99.2% concordance between HPV PCR-RDB testing and sequencing. In this studied population, the most common HR-HPV types were HPV-16, -52, -58, -18, -53, -33, and -51, rank from high to low. HPV-16, -18, -58, -59, and -33 were the top 5 prevalent genotypes in cervical cancer but HPV-16, -18, -59, -45, and -33 were the top 5 highest risk factors for cancer (odds ratio [OR]=34.964, 7.278, 6.728, 6.101, and 3.658; all p

The use of the human papillomavirus (HPV) vaccine was recently approved in Mainland China. This study determined the knowledge and attitudes of young women aged 20 to 35 years in Fujian Province, China, with regard to HPV and vaccination and explored the potential factors influencing their attitudes toward HPV vaccination. This was a cross-sectional study that collected data regarding the knowledge on and attitudes toward HPV and vaccination using questionnaires. Furthermore, the prevalence of HPV was determined from the sampled participants. A total of 1001 young women were included in the survey. This study demonstrated that the HPV prevalence rate was 15.7% (157/1001). Among all patients, 44.9% (n = 449) had heard of HPV; however, detailed knowledge about HPV was lacking. The majority (83.7%) expressed a willingness to be vaccinated. Specifically, knowledge of the dangers of HPV infection was significantly associated with the willingness to be vaccinated. In this study, women cited some concerns and expressed high expectations for the HPV vaccine, but the costs of vaccination reduced their willingness to be vaccinated. This study found that most patients did not have a detailed knowledge of HPV. Thus, there is a need for continued HPV promotion and education efforts, especially on the dangers of HPV infection, among young women aged 20 to 35 years in Fujian Province, China. Furthermore, it is important to subsidize the costs of vaccination for promoting vaccination campaigns in China.

More and more molecular drugs based on targeted therapy have been utilized in the treatment of gynecologic cancer, especially in ovarian cancer. In this article, we systematically review the current targeted therapeutic trials running in clinic. Large, randomized trials have been conducted in the treatment of ovarian cancer, endometrial cancer and cervical cancer by usingsmall molecule, antisense, mutational gene as well as antibodies. Other planned or ongoing trials currently targeted at molecular markers which may play important roles in gynecological carcinogenesis and progression suggest that combination chemotherapy with molecular targeted therapy will ultimately be an important option.

Objective. Interleukin 1 (IL-1) and IL-10 are critically involved in tumorigenesis. We investigated polymorphisms of IL-1 and IL-10 genes in patients with ovarian cancer (OC). Methods. In a prospective, case–control study 147 patients with OC and 129 patients without history of any malignancy (CG) were genotyped for IL-1 gene ( IL-1α −889 T/C and IL-1β −511 C/T) and IL-10 gene ( IL-10 −1082 G/A, −819 C/T and −592 C/A) using pyrosequencing. Results. IL-10 polymorphisms in −819 and −592 positions correlated with the postoperative residual tumor mass ( p =0.036 and p =0.035, respectively). The chance of achieving optimal tumor debulking was 1.49 times greater for patients with the C/C genotype at −819 and −512 positions than for patients with other genotypes. There were no significant associations between allelic frequencies for IL-1α and IL-1β in OC . IL-10 −819 CC and −592 CC genotypes were associated in univariate analysis with a better disease-free and overall survival. Conclusions. IL-10 promoter polymorphism may be related with the ability to achieve optimal tumor debulking. Polymorphism in IL-10 gene seems to influence the overall and disease-free survival rate. Subsequent multi-institutional studies with high number of patients are warranted to confirm these results.

Objective The aim of this study was to evaluate the clinicopahtological significance of telomerase activity and expression of hTERT gene in human ovarian cancer. The potential value of them as indicators for chemotherapy in ovarian cancer cells was also studied. Materials and methods A total of 73 samples and ovarian cancer cell lines HO-8910 and COC 1 were studied. Telomerase activity was detected by PCR-TRAP-ELISA assay and the expression of the hTERT mRNA was analyzed by semi-quantitative RT-PCR. Alteration of the telomerase activity and hTERT mRNA were also analyzed in the ovarian cancer cells treated with different concentration and different time of cisplatin. Cytogenetic analysis was performed to compare the telomere status in the OH-8910 cells pre- and post-cisplatin treatment. The associations between these two markers and cisplatin induced-apoptosis were respectively analyzed in COC 1 cells by the flow cytometry. Results Telomerase activity are highly increased in malignancy (0.795 ± 0.168 A450–655 nm ) than borderline (0.389 ± 0.174 A450–655 nm ), benign tumors (0.236 ± 0.102 A450–655 nm ) and normal ovary (0.213 ± 0.070 A450–655 nm ) ( p 0.05). Twenty samples showed detectable levels of hTERT. The hTERT gene positive lesion showed significantly higher telomerase activity than negative ( p = 0.004). There is a significant correlation between the telomerase activity and expression of hTERT ( r = 0.921). Both telomerase activity and expression of hTERT can reflect the chemotherapeutic effect of cisplatin in a time-dependent and dose-dependent manner. Treatment with 10 μM cisplatin, the hTERT mRNA decreased after 12 h and completely disappeared after 48 h, whereas the telomerase activity did not decrease until 24 h. Results from cytogenetic analysis and flow cytometry assay confirmed that the alterations of these two markers are associated with the anti-cancer treatment of cisplatin. Conclusion Expression of hTERT gene is rate-limiting with the activation of telomerase. Both of they may be useful in the predicting of chemotherapeutic effect in ovarian cancer.

Objectives: The fact that ovarian cancer remains confined to the peritoneal cavity even in advanced stages has allowed us to surmise that local immunosuppressive factors could be involved in the tumor biology of ovarian cancer. In this context, IL-10 can be one of the key factors. By studying the kinetics of IL-10 concentrations prior to and after surgery, this study attempts to reveal once more the ability of tumor micro-environment to produce IL-10. Some studies indicate that IL-10 concentration correlates with the tumor burden and can thus predict the surgical outcome. Data concerning this aim from patients with ovarian cancer do not seem to exist. Methods: In this prospective study, serum blood was collected from 27 patients, one day prior to surgery as well as 24 h, 4 and 8 days after surgery. The concentration of IL-10 was determined using ELISA. Results: While IL-10 levels rise within the first day post-OP, they are found to be reduced significantly when measured at later time points. IL-10 levels also correlate statistically significantly with the tumor grade, with lower IL-10 levels observed in well-differentiated and higher IL-10 levels in undifferentiated or only poorly differentiated tumors. Conclusion: IL-10 expression levels appear to be a good surrogate marker for tumor grading. If validated, this may in future contribute to the understanding of the biology stage cancers.

Cytokines play a major role in promoting the growth and metastatic spread of cancer cells. Interleukin-1 alpha and beta (IL-1) and IL-1 RA are known to be critically involved in carcinogenesis and in various solid tumors. There are limited data on expression of IL-1 alpha, beta and RA in serum and ascites in patients with advanced ovarian cancer. Objectives of this study were to investigate the level of IL-1 alpha, IL-1 beta and IL-1 RA in serum and ascites from patients with ovarian cancer and their impact on the prognosis.Fifty-three women with ovarian cancer (OC) (33 patients with primary OC and 20 with relapsed OC) and 50 women with benign gynaecological diseases as a control group (CG) were enrolled onto this prospective study. IL-1 alpha, beta and RA levels were analyzed in serum and ascites by ELISA technique.The median age was 55 years (range 19-80) in the ovarian cancer group and 40 years (range 15-89) in the controls. The distribution of histological type of ovarian cancer was as follows: serous-papillary 43 (81.1%), 4 (7.5%) mucinous, 3 (5.7%) endometroid and 3 (5.7%) clear cell carcinoma. The concentrations of IL-1 beta and RA in ascites or peritoneal fluid were significantly increased in patients with OC in comparison to the CG, for both cytokines (p0.0001); also the concentration of IL-1 RA in serum was increased in OC (p=0.003) vs. CG. An increased level of IL-1 beta in ascites correlated significantly with a poorer histopathological grading (p=0.038). IL-1 RA concentration in ascites was correlated with advanced FIGO stage (p=0.049) and the IL-1 RA serum level with ascites volume (or =500 ml vs.500 ml) (p=0.046). Patients with IL-1 RA level in ascites lower than the cut off value of 695.6 pg/ml showed a significant better progression-free median survival (24.6 vs. 12.8 months, p=0.008) and postoperative median overall survival (34.6 vs. 17 months, p=0.01) in comparison to patients with an IL-1 RA level in ascites higher than the cut off level. Additionally, a higher expression of IL-1 beta in serum (p=0.004) and ascites (p=0.05) reduced significantly the progression-free survival. In the multivariate analysis, expression of IL-1 RA in ascites was an independent prognostic factor for good progression-free and postoperative overall survival (HR, 0.39 95% CI, 0.18-0.83, p=0.01, HR, 0.36 95% CI, 0.16-0.8, p=0.01).IL-1 RA levels in ascites lower than the cut off value of 695.6 pg/ml are associated with a significant improvement in postoperative and progression-free survival. IL-1 RA shows a prognostic relevance in ovarian cancer.

Estrogen receptor-related receptor alpha (ERRalpha) was reported to compete with estrogen receptor alpha (ERalpha) in a constitutive manner as an orphan nuclear closely related to (ERalpha). To discuss the role of ERRalpha in the endometrial carcinoma cells, this study was performed. ER-responsive endometrial carcinoma cells Ishikawa and ER-nonresponse HEC-1A cells were treated with different concentration of 17beta-E2 or E2 plus ICI 182780. Semiquantitative reverse transcription-polymerase chain reaction and western blot were performed to analysis the expression of human estrogen receptor-related receptor alpha (hERRalpha). Plasmid PLXSN-hERRalpha was constructed and transfected into cells. Selected in the medium containing high-dose G418, the Ishikawa and HEC-1A cells with stable overexpression of hERRalpha were constructed and renamed as Ishikawa/hERRalpha and HEC-1A/hERRalpha, respectively. To discuss the effect of overexpression of hERRalpha in the cell biological behavior (3-[4,5-dimethylth-lazol-2yl]-2,5-diphenyltetrazolium bromid) (MTT) cell assay was performed. Estrogen downregulates ERRalpha expression in ER-positive Ishikawa cells, while upregulates the expression of ERRalpha in ER-negative HEC-1A cells. In Ishikawa cells, the downregulation of 17beta-E2 in ERRalpha expression cells could be blocked by ICI 182780. A decreasing expression of hERalpha was observed in the ER-responsive cells with overexpression of ERRalpha (Ishikawa/hERRalpha). Overexpression of hERRalpha inhibits the cell proliferation in the ERalpha-responsive Ishikawa cells and stimulated the cell proliferation in the ERalpha-nonresponsive HEC-1A cells. Function of hERRalpha depends on the expression and function of hERalpha. ER-mediated signaling might be the important factor resulting in the hormone-dependent endometrial carcinoma, whereas ERRalpha-mediated pathway might act as the vital role in hormone-independent endometrial carcinoma.

Estrogen receptor-related receptors (ERRs) are members of orphan nuclear receptors closely related to the estrogen receptors (ERs). Researches showed that the ERRs bound to estrogen response elements and interfered in the ER signal pathway. Therefore, it might be associated with estrogen-dependent diseases. The purpose of this study was to explore whether ERRs were involved in the tumorigenesis of endometrial adenocarcinoma. We examined the expression of ERRs in endometrial adenocarcinoma and normal endometrium using semiquantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Clinicopathologic features including FIGO stage, histologic grade, myometrial invasion, and nodal metastasis were reviewed. Results showed that messenger RNA (mRNA) levels of ERRalpha, ERRbeta, and ERRgamma were positively associated with the immunoreactivities (P= 0.009, P= 0.014, and P= 0.001, respectively). The expression rate and relative level of ERRalpha mRNA in ERalpha-positive endometrial adenocarcinomas were lower than in normal endometriums (P= 0.049 and P= 0.023), whereas the relative level of ERRgamma mRNA in ERalpha-positive endometrial adenocarcinomas was higher than in normal endometriums (P= 0.014). Expression of ERRalpha mRNA was positively correlated with FIGO stage (P= 0.019) and myometrial invasion (P= 0.043). A negative correlation was observed between expression of ERRgamma mRNA and nodal metastasis (P= 0.021). Results suggested that ERRalpha and ERRgamma might participate in the tumorigenesis of endometrial adenocarcinoma. ERRalpha and ERRgamma are promising to be new prognostic factors in endometrial adenocarcinoma.

10585 Background: Recently, we have identified for the first time a new putative phosphodiesterase named edi-3 that correlates with tumorigenesis in endometrial cancer. In the present study we analyzed the prognostic relevance of edi-3 in ovarian cancer. Methods: Edi-3 mRNA expression was measured by quantitative RT-PCR (TaqMan) in 62 patients with primary ovarian cancer. All patients signed informed consent, approved by the Clinical Review Board and Ethics Committee of the Medical University Berlin, Charité, Germany. The tumor specimens were collected according to the Tumor Bank Ovarian Cancer standard operating procedures. A validated systematic intraoperative documentation tool was used for the detailed documentation of all surgical procedures. Using the multivariate proportional hazard model we analyzed whether edi-3 predicts survival independent from FIGO-stage, grading, postoperative residual disease and histological type. Results: Edi-3 expression is associated with survival in the univariate Cox model (hazards ratio [HR]: 1.488, 95% confidence interval [CI]: 1.131 - 1.959, P=0.005). Interestingly, edi-3 was also predictive in the multivariate proportional hazard model adjusted for the conventional clinical factors (HR: 1.521, CI: 1.107 - 2.090, P=0.010). Conclusions: Edi-3 is a new independent prognostic factor in primary ovarian cancer with HR=1.5 (P=0.010). Its function, a possible role in inositol phosphate metabolism, will be further explored in a multi-instutional setting. No significant financial relationships to disclose.

20094 Background: IL1 and IL10 are overexpressed in 55% to 98% of advanced epithelial OC. Different studies demonstrated IL1 and IL10 as independent prognostic factors for OC. This study was performed to investigate the influence of plms of IL-1A, IL-1B and IL-10 gene on the occurrence tumor biology of OC. Methods: In a prospective, monocentric, case-control study 147 pts with OC (71 pts with primary OC and 77 pts with recurrent OC) and 129 pts with no history of malignancies were genotyped for plms of the IL-1 gene (IL-1A -889 T/C and IL-1B -511 C/T promoter) and IL-10 gene (IL-10 -1082 G/A, -819 C/T and -592 C/A). All pts were collected within Tumor bank Ovarian Cancer Project. Genomic DNA fragments were amplified by PCR and the allele sequences were obtained by pyrosequencing. We analyzed significance using the Chi-Square by Pearson and Fisher’s exact test. Statistical significance was determined by Mann-Whitney test. A two-tailed p value No significant financial relationships to disclose.

13127 Background: The EGFR is over expressed in 55% to 98% of advanced epithelial ovarian carcinoma. Different studies demonstrated EGFR status as an independent prognostic factor for OC. Recent studies in non small cell lung cancer suggest that the presence of the clinical response to tyrosine kinase inhibitors (e.g. ZD 1839) correlates with the somatic mutations in the kinase domain of EGFR, exons 18–21. For pts with OC data are not available on EGFR gene mutation. Methods: Shock-frozen samples from 32 patients (pts) with primary of ovarian cancer were stratified in two groups according to disease-free interval: ≤6 months (17 pts.) and No significant financial relationships to disclose.

9628 Background: The plasminogen activator-plasmin cascade plays a central role in tumor cell invasion and metastasis of solid tumors. The type-1 plasminogen activator inhibitor (PAI-1) is the majo...

9643 Background: Interleukin-1β (IL-1) and IL-1 RA are known to be critically involved in ovarian carcinogenesis. There are limited data on the expression of IL-1 β and RA in ascites in pts with OC...