Knockdown of circular RNA (CircRNA)_001896 inhibits cervical cancer proliferation and stemness in vivo and in vitro

Objective:Previous studies indicated that aberrant circular RNA(circRNA)expression affects gene expression regulatory networks,leading to the aberrant activation of tumor pathways and promoting tumor cell growth.However,the expression,clinical significance,and effects on cell propagation,invasion,and dissemination of circRNA_001896 in cervical cancer(CC)tissues remain unclear.Methods:The Gene Expression Omnibus(GEO)datasets(GSE113696 and GSE102686)were used to examine differential circRNA expression in CC and adjacent tissues.The expression of circRNA_001896 was detected in 72 CC patients usingfluorescence quantitative PCR.Correlation analysis with clinical pathological features was performed through COX multivariate and univariate analysis.The effect of circRNA_001896 downregulation on CC cell propagation was examined using the cell counting kit-8(CCK-8)test,clonogenic,3D sphere formation,and in vivo tumorigenesis assays.Results:Intersection of the GSE113696 and GSE102686 datasets revealed an increased expression of four circRNAs,including circRNA_001896,in CC tissues.Fluorescence quantitative PCR confirmed circRNA_001896 as a circular RNA.High expression of circRNA_001896 was considerably associated with lymph node metastasis,International Federation of Gynecologists and Obstetricians(FIGO)stage,tumor diameter,and survival period in CC patients.Proportional hazards model(COX)univariate and multivariate analyses revealed that circRNA_001896 expressions are a distinct risk factor affecting CC patients’prognosis.Cellular functional experiments showed that downregulating circRNA_001896 substantially suppressed CC cell growth,colony formation,and 3D sphere-forming ability.In vivo,tumorigenesis analysis in nude mice demonstrated that downregulating circRNA_001896 remarkably reduced the in vivo proliferation capacity of CC cells.Conclusion:CircRNA_001896 is highly expressed in CC tissues and is substantially related to lymph node metastasis,FIGO stage,tumor size,and survival period in patients.Moreover,downregulating circRNA_001896 significantly inhibits both in vivo and in vitro propagation of CC cells.Therefore,circRNA_001896 might be used as a biomarker for targeted therapy in cervical cancer.

Subgroups of peripheral immune effector cells in cervical cancer patients are more sensitive to radiation therapy than chemotherapy

Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.

Relationship between Circulating Plasma Galectin-3 Levels and T-Cell Activation during Cervical Cancer Chemotherapy

Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical response to chemotherapy. This work examines plasma levels of galectin-3 (Gal-3) and percentages of activated T cells in patients with cervical cancer treated with chemotherapy and investigates if there is a relationship between the rates of these two elements. Methods: We compared data from 37 patients with cervical cancer undergoing chemotherapy and 42 controls with normal cervical cytology. Plasma Gal-3 concentrations were assessed by ELISA and expression of activation markers by T cells (CD69 and HLA-DR) was assessed by flow cytometry at three different time points during chemotherapy. Results: Our results showed that patients had a significantly higher concentration of Gal-3 compared to controls (4.025 vs. 1.340, p 0.001), similarly, they had a significantly high percentage of activated lymphocytes (2.610 vs. 0.731;p 0.0001). According to the response to treatment, patients with no response to treatment had a lower concentration of circulating Gal-3 but had approximately the same percentage of activated CD4 and CD8 lymphocytes as patients with a partial or total response. In addition, we found a positive correlation between the Gal-3 level and CD4 T cells expressing the activation marker CD69 (p 0.05;rho = 0.44). Conclusion: In conclusion, our results show that there would be a relationship between circulating galectin-3 and the percentage of peripheral CD4+CD69+ cells in cervical cancer.

Relationship between the Expression of Telomerase and Human Papillomavirus Infection in Invasive Uterine Cervical Carcinoma

Telomerase activity was examined in invasive cervical carcinoma to assess whether it is activated during cervical malignant transformation and to look for its possible association with human papillomavirus （HPV） infection. Histologically confirmed invasive cervical carcinomas and benign cervices were assayed for telomerase activity by using a modified telomere repeat amplification protocol （TRAP）. The same cases were subjected to polymerase chain reaction （PCR） detection of HPV by using consensus primers and type-specific （HPV types 16 and 18） primers. Telomerase activity was detected in 40 of 45 （88.9%） invasive cervical carcinomas and 2 （all chronic cervicitis） of 50 （4%） benign cervical lesions. HPV was detected in 36 （24 HPV-16 and 4 HPV-18 cases） of 45 （80%） invasive cervical carcinomas and 20 （11 HPV-16 and 1 HPV-18 cases） of 50 （40%） benign cervical changes. There was a significant correlation between the expression of telomerase with histological grade （φ=0.44, P〈0.005）, but no correlation was found between telomerase expression and HPV-18 （P〉0.05）. Although larger sample studies are needed, there seems to be a clear association between telomerase upregulation and HPV status, mainly HPV-16 infection.

LOSS OF HETEROZYGOSITY ON CHROMOSOME 17p13.3 IN OVARIAN CANCER AND CERVICAL CANCER

Objective: To identify the loss of heterozygosity (LOH) on chromosome 17p13 3 in ovarian cancer and cervical cancer Methods: The frequency of LOH on chromosome 17p13 3 in DNA samples from 24 ovarian cancers, 9 cervical cancers, and 13 non malignant gynecological diseases were determined respectively, using Southern blot method with probe PYNZ 22 Results: LOH on 17p13 3 was found in 12 of 24 (50 0%) ovarian cancers (including a borderline mucinous cystadenoma), 4 of 9 (44 4%) cervical carcinomas, and 1 of 13 (7 7%) non malignant gynecological diseases, which was cervical intraepithelial neoplasm III (CIN III) ( P< 0 01) Conclusion: These results show that LOH on 17p13 3 is associated with ovarian cancer and cervical cancer, suggesting that detection of LOH on 17p13 3 may be helpful to understand the molecular pathogenesis of ovarian cancer and cervical cancer

Mechanism of anti-tumor effect of HIF-1α silencing on cervical cancer in nude mice

Objective： The aim of our study was to observe the anti-tumor effect of silencing the expression of HIF-1α on cervical cancer in nude mice and to explore its mechanism of action. Methods： Human cervical cancer cell line Siha cells were divided into 3 groups： mock control group, control group transfected with scrambled sequence plasmid, and experimental group transfected with pU-HIF-la-shRNA eukaryotic expression plasmid. Cultured cells of the three groups were inoculated in nude mice to establish cervical cancer-bearing nude mice. HIF-la RNAi assay was performed to evaluate the tumor-suppressive effect of HIF-1α silencing on cervical cancer-bearing nude mice. Immunohistochemistry and Western blot were used to observe the distribution and protein expression of HIF-1α and GLUT1, while RT-PCR was adopted to detect the gene expression of HIF-1α, GLUTI and HK I1. The product of glycolysis （tactic acid） and apoptosis in tumor cells were detected by colorimetry and semi-quantitative TUNEL staining, respectively. Results： The tumor growth in experimental group was significantly slower than that in the two control groups （P 〈 0.05）. In the 50th day after transplantation, the tumor weight in the experimental group was （1.90 ± 0.28） g, significantly lower than （2.95 ± 0.77） g in the control group and （2.54 ± 0.56） g in the mock group （P 〈 0.01）. In the experimental group, the gene and protein levels of HIF-1α were 0.45 ± 0.04 and 1.25 ± 0.92, and the levels of GLUT1 were 0.32 ± 0.02 and 1.25 ± 0.48, respectively. Both indicators in HIF-la and GLUT1 were lower than that in the two control groups （P 〈 0.05）. The expression levels of HK Ⅱ gene and lactic acid in the experimental group were lower than that in the two control groups （P 〈 0.05）, but the apoptotic cells were much more numerous in the experimental group than that in matched control groups （P 〈 0.01）. Conclusion： The 9ene therapy by siRNAtargeted silencing of HIF-1α may down-regulate its downstream genes GLUT1 and HK Ⅱ expression, therefore, to reduce the tumor glycolysis activity and promote tumor cell apoptosis, and exert a tumor-suppressing effect in vivo.

Incidence and mortality of cervical cancer in China in 2015

Objective:To estimate the incidence and mortality of cervical cancer in China based on the cancer registration data in 2015,collected by the National Central Cancer Registry(NCCR).Methods:There were 501 cancer registries that submitted data to the NCCR,whose data were the basis for estimating the incidence and mortality of cervical cancer in China in 2015.After evaluating the data quality,368 registries’data were accepted for the analysis and stratified by area(urban/rural)and age group.Combined with data on the national population in 2015,the nationwide incidence and mortality of cervical cancer were estimated.Cervical Cancer cases of 22 cancer registries were applied for temporal trends from 2000 to 2015.The Chinese population census in 2000 and Segi’s population were used to calculate age-standardized incidence and mortality rates.Results:An estimated 111,000 new cases were attributed to cervical cancer in China in 2015,accounting for 6.24%of all female new cancer cases in that year in China.The crude rate(CR)of incidence and age-standardized incidence rates by the China standard population(ASIRC)and by Segi’s world standard population(ASIRW)of cervical cancer were 16.56/100,000,11.78/100,000,and 10.86/100,000,respectively.The cumulative incidence rate from birth to 74 years old was 1.15%,whereas the calculation of incidence rates over the truncated age range of 35-64 years by Segi’s world standard population(T-ASIRW)was 27.66/100,000.The estimates of cervical cancer deaths were about 33,800 and 3.94%of all female cancer-related deaths in China in 2015,with a crude mortality rate of 5.04/100,000.The age-standardized mortality rates adjusted by the Chinese standard population(ASMRC)and by world Segi’s population(ASMRW)were 3.29/100,000 and 3.15/100,000,respectively,with a cumulative mortality rate(0-74 years old)of 0.35%.Both the incidence and mortality were higher in rural than in urban areas.The age-specific cervical cancer incidence significantly increased with age,particularly after age 25 years,and peaked at 50-54 years old,whereas age-specific mortality increased rapidly after 35 years old,peaking at 80-84 years old.The age-standardized incidence rates increased by about 8.6(95%CI:6.9,10.3)per year during the period of 2000−2015.The age at diagnosis of patients with cervical cancer tended to be younger.In rural areas,the mean age at diagnosis decreased about 3.22 years from 2000 to 2015(𝛽=-0.33,P<0.001).Conclusions:China has a high burden of cervical cancer and important disparities among different regions.Es-pecially in the middle and western areas and rural areas,cervical cancer is a serious issue in women’s health,and prevention strategies need to be enhanced.Prevention and control strategies need to be enhanced and imple-mented with reference to local status,such as human papillomavirus(HPV)vaccination and screening programs.

Relationship between Cell Proliferation and Apoptosis in Cervical Carcinoma

Objective To study the relationship between cell proliferation and apoptosis in cervical carcinoma and its clinical significance. Methods The cell proliferation and apoptosis of cervical epithelial cells in archival formalin-fixed, paraffin-embedded tissue sections of normal cervix, cervical intraepithelial neoplasms (GIN) and cervical squamous carcinoma were tested by using immunohistochemistry assay and DNA nick end-labeling technigue. The proliferation index (PI) and apoptosis index (AI) were calculated and their correlation with clinical and pathological data was analyzed.Results PI was gradually increased, but the AI and AI/PI ratio decreased from normal cervical epithelium, GIN to cervical carcinoma. There was no significant relationship among cell proliferation, apoptosis, clinical stages and pathological grades. High AI was always associated with a poor prognosis of the patients.Conclusion Cell proliferation and apoptosis allow to distinguish among normal epithelium, GIN and cervical carcinoma and are useful for the assessment of the malignant potential of tumor tissues.

Expression and clinical significance of dendritic cell and transforming growth factor-beta 1 in cervical cancer

Objective:To explore the density and mature status of Dendritic cell(DC) in cervical cancer and correlation with the expression of transforming growth factor-beta 1(TGF-β1).Methods:Streptavidin-peroxidase(SP) immunohistochemistry methods were used to detect S-100 DC and the expression of TGF-β1 in 20 normal cervical tissues and 53 cervical cancer tissues without any sort of chemotherapy or radiation therapy prior to resection.Medical records were reviewed,clinicopathological variables were retrieved and used for analysis.Results:Two types of DC were observed under the microscope.The expression of DC in cervical cancer was significantly higher than that in normal tissues(23.34 cells/mm^2 vs 29.91 cells/mm^2,P<0.05),and significantly higher in early stage than that in advanced stage(P<0.05).The expression of TGF-β1 was significantly higher in cervical cancer than that in normal tissues (P<0.025).However,there was no correaction between TGF-β1 and lymph nodes metastasis.The index of DC in cervical cancer was negatively correlated to the expression of TGF-β1 in tumor cells (r=-0.8875,P=0.0001).Conclusion:Maturation of DC in cervical cancer is inhibited.The decreased number of DC and the higher expression of TGF-β1 are due to the failure of the immunity,these may play an important role in the development of the cervical cancer.

Quantitative Detection of Screening for Cervical Lesions with ThinPrep Cytology Test

OBJECTIVE To investigate the available parameters in gynecological screening for cervical lesions by liquid-based cytology technology （ThinPrep Cytology Test, TCT） and The Bethesda System （TBS）, also with computer image analysis. METHODS With application of the image analysis system, all grades of cervical lesion cells were detected quantitatively and sorted in atypical squamous cells of undetermined significance （ASCUS）, atypical squamous cells-cannot exclude HSIL （ASC-H）, low-grade squamous intraepithelial lesion （LSIL）, high-grade squamous intraepithelial lesion （HSIL） and cervical squamous cell carcinoma （SCC） with the mean optical density （MOD）, average grey （AG）, positive units （PU）, and nucleus to cytoplasmic ratio （N： C）. Differences between each group of cells were compared and analyzed statistically. RESULTS Apart from four stereologic parameters in LSIL and HSIL groups there were no differences among them, in the other groups, there was statistically significant in differences between MOD, AG and PU values. Differences between them in the ratio of nucleus to cytoplasm were highly statistically significant. CONCLUSION Stereological indexes may serve as a screening tool for cervical lesions. The image analysis system is expected to become a new means of cytological assisted diagnosis.

Prognostic evaluation of postoperative adjuvant therapy for operable cervical cancer:10 years'experience of National Cancer Center in China

Objective： The aim of this study was to investigate the prognostic factors and to evaluate the impact of adjuvant therapy on clinical outcome for early-stage cervical cancer. Methods： The clinical-pathological data of all 1,335 patients with the International Federation of Gynecology and Obstetrics （FIGO） Ib-[Ia cervical cancer treated with primary radical surgery at the Chinese National Cancer Center between May 2007 and Dec 2013 were retrospectively reviewed. The median follow-up was 70 months. Results： Of all the patients, 61.6% of the cases received adjuvant therapy, with 5-year disease-free survival （DFS） of 92.1% and 5-year overall survival （OS） of 95.0%. In multivariate analysis, differentiation of G3 （P〈0.05）, lymph node metastasis （LNM, P〈0.05） and lymphovascular space invasion （LVSI, P〈0.05） were independent predictors for OS, while LNM （P〈0.05）, deep stroma invasion （DSI, P〈0.05） and LVSI （P〈0.05） were independent factors for DFS. The samples were stratified by histologic type, and cervical squamous cell carcinoma （SCC） was found to share the same independent factors except for differentiation of OS. As to patients with cervical adenocarcinoma/adenosquamons carcinoma （AC/ASC）, differentiation was the independent predictor of OS （P〈0.05）; and LVSI of DFS （P〈0.05）. Of 236 patients with high-risk factors, there was no significant difference in survival between concurrent chemoradiotherapy （CCRT, n=195）, radiotherapy （RT, n=24）, and chemotherapy （CT, n=17）. Among the 190 patients with LNM who underwent CCRT, 124 cases showed improved DFS after sequential CT （P=0.118）, with a recurrence rate decrease of 14%, though the difference was not statistically significant. Patients with single intermediate-risk factors like DSI or LVSI were found to partially benefit from adjuvant therapy, but the difference was not statistically significant. Conclusions： LNM, LVSI, DSI and differentiation were found to be independent prognostic factors for operable cervical cancer. Aggressive postoperative adjuvant therapy based on single risk factors in Chinese National Cancer Center could benefit survival. CCRT＋CT outperformed CCRT in high-risk patients. For patients with single non-high-risk factor, the role of adjuvant therapy needs to be further discussed.

Separate lateral parametrial lymph node dissection improves detection rate of parametrial lymph node metastasis in early-stage cervical cancer: 10-year clinical evaluation in a single center in China

Objective: To investigate the clinical significance of separate lateral parametrial lymph node dissection(LPLND) in improving parametrial lymph node(PLN) and its metastasis detection rate during radical hysterectomy for early-stage cervical cancer.Methods: From July 2007 to August 2017, 2,695 patients with cervical cancer in stage IB1-IIA2 underwent radical hysterectomy were included. Of these patients, 368 underwent separate dissection of PLNs using the LPLND method, and 2,327 patients underwent conventional radical hysterectomy(CRH). We compared the surgical parameters, PLN detection rate and PLN metastasis rate between the two groups.Results: Compared with CRH group, the rate of laparoscopic surgery was higher(60.3% vs. 15.9%, P<0.001),and the blood transfusion rate was lower(19.0% vs. 29.0%, P<0.001) in the LPLND group. PLNs were detected in 356 cases(96.7%) in the LPLND group, and 270 cases(11.6%) in the CRH group(P<0.001), respectively. The number of PLNs detected in the LPLND group was higher than that in the CRH group(median 3 vs. 1, P<0.001).The PLN metastases were detected in 25 cases(6.8%) in the LPLND group, and 18 cases(0.8%) in the CRH group(P<0.001), respectively. In multivariable analysis, LPLND is an independent factor not only for PLN detection [odds ratio(OR)=228.999, 95% confidence interval(95% CI): 124.661-420.664;P<0.001], but also for PLN metastasis identification(OR=10.867, 95% CI: 5.381-21.946;P<0.001).Conclusions: LPLND is feasible and safe. The surgical method significantly improves the detection rate of PLN and avoids omission of PLN metastasis during radical hysterectomy for early-stage cervical cancer.

Human Papillomavirus 16 E6,E7 siRNAs Inhibit Proliferation and Induce Apoptosis of SiHa Cervical Cancer Cells

Objective： To evaluate the effects of HPV16 E6/E7 siRNAs on cervical cancer SiHa cells. Methods： The expressions of the E6, E7, p53 and Rb genes were assayed by RT-PCR and Western-bloting respectively. The proliferation and apoptosis of the cells were evaluated by MTT and flow cytometry. Results： HPV 16 E6 and E7 oncogenes were selectivly downregulated by HPV 16 E6 and E7 siRNAs, which sustained at least 96 h by single dose siRNA. Furthermore, reduction of E6 and E7 oncogenes expression upregulated the expressions of P53 and RB protein and induced apoptosis in SiHa cells. Conclusion： Introduction of HPV16 E6/E7 siRNA might be a potentially potent and specific approach to inhibit proliferation and induce apoptosis of SiHa cervical cancer cells.

Dosimetric analysis of tomotherapy-based intensity-modulated radiotherapy with and without bone marrow sparing for the treatment of cervical cancer

Objective The aim of the study was to compare tomotherapy-based bone marrow-sparing intensity-mod- ulated radiotherapy （BMS-IMRT） with intensity-modulated radiotherapy （IMRT） without entering the pelvic bone marrow as a planning constraint in the treatment of cervical cancer after hysterectomy. Methods BMS-IMRT and IMRT plans were designed for a cohort of nine patients. The prescribed dose was 45 Gy in 1.8 Gy daily fractions, and 95% of the planned target volume received this dose. The doses were computed using a commercially available treatment planning system with the convolution/superposition algorithm. Plans were compared according to dose-volume histogram analysis in terms of planning target volume homogeneity and conformity indices （HI and CI） as well as organ at risk dose and volume parameters. Results BMS-IMRT had advantages over IMRT in terms of CI, but was equivalent to the latter in H1. V5, V10, V20, V30, and V40 of pelvic bone marrow in BMS-IMRT decreased by 0.06%, 17.33%, 22.19%, 13.85%, and 16.46%, respectively, compared with IMRT. Except for V30 of the small bowel and V30 and V40 of the bladder, no statistically significant differences were found between BMS-IMRT and IMRT in the small bowel, bladder, and rectum. Conclusion For cervical cancer patients receiving tomotherapy-based radiotherapy after hysterectomy, BMS-IMRT reduced pelvic bone marrow volume receiving low-dose radiation, and it may be conducive to preventing acute hematologic toxicity.

Prognostic Factors for Patients with FIGO Stage-IB Cervical Squamous Cell Carcinoma:Does the Tumor Size(≤4 cm or>4 cm)Really Matter?

OBJECTIVE To investigate the factors that can accurately predict the prognosis for patients with FIGO stage-IB cervical squamous cell carcinoma treated with radical surgery. METHODS A retrospective analysis of clinical data from 174 cases of FIGO Stage-IB cervical squamous cell carcinoma treated in our institute was conducted. RESULTS The 5-year overall disease-free survival of the patients was 79.4% and the recurrence rate was 16.7%. Seventy-five percent of the 60 patients with a tumor 〉 4 cm and 28.1% of the 114 patients with a tumor ≤ 4 cm received preoperative radiotherapy, resuting in a significant difference between the two groups （P 〈 0.001）. The 5-year disease-free survival rate for the groups with a tumor ≤ 4 cm without and with preoperative radiotherapy, and with a tumor 〉 4 cm without and with preoperative radiation therapy were 80.5%, 85.2%, 69.3% and 77.1%, respectively. There was no significant difference between any of the groups （P 〉 0.05）. A univariate analysis showed that pelvic node metastasis, a positive parametrial surgical margin and postoperative adjuvant therapy were all significantly correlated with the 5-year disease-free survivals （P 〈 0.05）. Multivariate analysis revealed that pelvic node metastasis （P = 0.004） and a positive parametrial surgical margin （P = 0.040） were independent factors that influenced the prognosis. The 5-year disease-free survivals for the cases with a tumor ≤ 4 cm and 〉 4 cm were 57.4% and 44.7% respectively in the high-risk group （patients with pelvic lymphatic metastasis and/or positive parametrial surgical margin） （P=0.575） and the recurrence ratio was 7/18 and 6/14 for the cases of the two tumor sizes in the same risk group. There was no significant difference between the two groups （P=0.821）. The 5-year disease-free survivals for the cases with a tumor ≤ 4 cm and 〉 4 cm were 86.5% and 82.9% respectively in the low-risk group （patients without pelvic lymph-node metastasis and/or positive parametrial surgical margin）, respectively （P 〉 0.05） and the recurrence ratio was 9/95 and 7/47 for the cases of the two tumor sizes in the same risk group. There was no significant difference between the two groups （P 〉 0.05）. CONCLUSIONS For FIGO Stage-IB cervical squamous cell carcinoma patients with radical surgery as the major means of treatment, the features of pelvic lymph-node metastasis and a positive parametrial surgical margin are independent factors that influence the prognosis. The tumor size can not be used as a criterion for predicting the prognosis.

Limited energy parametrial resection/dissection during modified laparoscopic nerve-sparing radical hysterectomy

Objective: The aim of this study was to investigate the feasibility of using ultrasonic scalpel combined with vascular clip in parametrial management,called limited energy parametrial resection/dissection(LEPRD),in laparoscopic nerve plane-sparing radical hysterectomy(NPSRH),a modified nerve-sparing radical hysterectomy(NSRH); and to evaluate its effectiveness in pelvic autonomic nerve preservation.Methods: From July 2012 to January 2016,257 consecutive patients with stage IB1 to IIA2 cervical cancer who underwent NPSRH were included in this study.Patients were divided into three cohorts according to the different parametrial resection modality.The clinical,pathological and surgery-related parameters were compared between the three groups.Short-and long-term postoperative bladder functions were evaluated.Results: LEPRD was attempted in 94 patients,and was successful in 65(69.1%) patients(LEPRD group).The remaining 29(30.9%) patients required bipolar coagulation after failure of vascular clipping(combined modality group).Routine bipolar cautery was used in the other 163 patients during the parametrial resection(bipolar group).The blood loss in the LEPRD group was significantly lower than those in the other two groups(P<0.001).The rate of successful Foley removal on postoperative day 7 was significantly higher in the LEPRD group than in the bipolar group(P=0.022).The incidence of chronic voiding dysfunction was significantly lower in the LEPRD group than in the bipolar group(P=0.019).Conclusions: It is feasible to perform LEPRD in NPSRH for cervical cancers.This kind of limited energy surgical technique is associated with less blood loss,and leads to improved postoperative bladder function.

CLINICAL ANALYSIS OF PRIMARY MALIGNANT MELANOMA OF THE CERVIX

Objective To investigate the clinical and pathological characteristics of primary cervical malignant melanoma, and its prognosis. Mothods The clinical and pathological data of four patients with primary malignant melanoma of the cervix were analyzed retrospectively. Nerve tissue protein S-100 and monoclonal antibody to melanoma （HMB-45） were measured in all cases by immunohistochemical method. All four patients received radical hysterectomy. Three of them received chemotherapy preoperation or postoperation, and one of them received biotherapy with interferon-3, and interleukin-2 at the same time. All the cases were followed up. Results The average age of four patients was 45 years. Clinical symptoms presented with irregular vaginal bleeding, postcoital bleeding, or increase of vaginal discharge. Gynecologic examination showed polypus papilla cauliflower-shaped or nodulated black-brown or black-blue mass on the cervix. All the four cases were pathologically diagnosed with cervical malignant melanoma. S-100 and HMB-45 were positive in all patients. Two patients died at 6 and 41 months postoperation, respectively. The other two patients survived for 3.5 and 7 years postoperation, respectively. Conclusion S-100 protein and HMB-45 play very important roles in the diagnosis of primary malignant melanoma of cervix. Radical hysterectomy, chemotherapy combined with dimethyl triazemo imidazole carboxamide and biological therapies may improve the prognosis of the primary malignant melanoma of cervix if the disease could be diagnosed in an early stage.

Clinical value of three-dimensional conformal radiation therapy for postoperation cervix cancer

Objective： To observe the clinical value of three dimensional conformal radiation therapy （3D-CRT） followed by radical surgery and discuss the best radiation technique for cervical cancer patients after radical hysterectomy. Methods： From February 2003 to June 2006, 115 stage Ⅰ-Ⅲa uterus cervix cancer patients received postoperation radiotherapy in our department after radical surgery. They were randomly divided into two groups. There were 81 patients in 3D-CRT group and 74 patients in traditional radiation group. According to FIGO, there were 45 in stage Ⅰ, 77 in stage Ⅰa, 31 in stage Ⅱb, 2 in stage Ⅲa. Pathological examination confirmed that 148 cases had squamous carcinoma and 7 cases had adenocarcinoma. The target volume included supravaginal portion, the cervical stump, paracervical tissue, common iliac lymph nodes, intemal and extemal lilac lymph nodes, obturator and sacral lymph nodes. For 3D-CRT group we designed four-field or two-fields rotating irradiation in the left-right and the anterior-posterior direction. For traditional radiation group we designed two-field, anterior-posterior, at opposed lateral directions. The radiation dose ranged from 48-50 Gy. Stage lib patients with a cervical stump recurrence received postoperative boost radiation by 8-10 Gy. Results： There were no significant difference in 0.5-year, 1-year, 1.5-year, 2-year local control rate between 3D-CRT group and traditional radiation group （P 〉 0.05）. The occurrence of early and late complications was significant lower in 3D-CRT group than that in traditional radiation group （P 〈 0.05）. There was significant difference in gastrointestinal reaction and urinary system reaction between the two groups （P 〈 0.05）. In postoperation radiotherapy 3D-CRT was superior compared with traditional two-field radiation at opposed lateral direction. Conclusion： 3D-CRT is superior compared with traditional radiation. Four-field rotating irradiation in 3D-CRT has advantages of dose focusing, even dose distribution and cause less side effects and complications. The side-field and cervical stump-targeted boost irradiation are apparent advantages of 3D-CRT.

Prevalence of high-risk human papillomavirus infection in different cervical lesion among organized health-examination women in Shanghai, China

Background Cervical cancer is the second most common cause of death from cancer among women worldwide. Human papillomavirus （HPV） plays a central role in the etiology of cervical cancer. It is important to describe the prevalence of HPV infection in different types of cervical lesions and to explore the relation between HPV viral load and the severity of cervical lesions. Methods To describe the HPV infection prevalence and viral load in different age groups, we retrospectively investigated 6405 cases of women who were organized by their units to take health-examination. They were given Hybrid Capture II tests between January 2005 and December 2006. The correlation between HPV viral load and pathology was assessed. Results Overall HPV infection prevalence was 29.1% （1864/6405）, while in women 18-20 years old it was 54.4% （31/57）, the highest among all age groups. After declining rapidly, HPV prevalence stabilized at about 30.0% in women aged 30 and older. Of the 6405 women, 1483 women had a colposcopic biopsy and 33.2% （492/1483） were positive for HPV DNA. Twenty-one percent of women with a normal diagnosis （238/1095） had HPV infection, a statistically significantly lower prevalence than in women with cervical lesions, including those with cervical intraepithelial neoplasia （68.8% in CIN1,66.7% in CIN2, and 76.5% in CIN3） or with cervical cancer （94.1%）. The correlation coefficient between viral load and cervical lesion severity was 0.134, which was not statistically significant （P=0.075）. Viral load values in women with CINs and cervical cancer were calculated, and no significant differences were identified. Conclusions The prevalence of high-risk HPV infection among women attending hospitals for health-examination in Shanghai is similar to the worldwide rate. HPV viral load can distinguish cervical lesions from normal individuals but cannot adequately predict the severity of cervical lesions.