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The focus of this study is the anti-cancer effects of Cudrania tricuspidata stem (CTS) extract on cervical cancer cells. The effect of CTS on cell viability was investigated in HPV-positive cervical cancer cells and HaCaT human normal keratinocytes. CTS showed significant dose-dependent cytotoxic effects in cervical cancer cells. However, there was no cytotoxic effect of CTS on HaCaT keratinocytes at concentrations of 0.125-0.5 mg/mL. Based on this cytotoxic effect, we demonstrated that CTS induced apoptosis by down-regulating the E6 and E7 viral oncogenes. Apoptosis was detected by DAPI staining, annexin V-FITC/PI staining, cell cycle analysis, western blotting, RT-PCR, and JC-1 staining in SiHa cervical cancer cells. The mRNA expression levels of extrinsic pathway molecules such as Fas, death receptor 5 (DR5), and TNF-related apoptosis-inducing ligand (TRAIL) were increased by CTS. Furthermore, CTS treatment activated caspase-3/caspase-8 and cleavage of poly (ADP-ribose) polymerase (PARP). However, the mitochondrial membrane potential and expression levels of intrinsic pathway molecules such as Bcl-2, Bcl-xL, Bax, and cytochrome C were not modulated by CTS. Taken together, these results indicate that CTS induced apoptosis by activating the extrinsic pathway, but not the intrinsic pathway, in SiHa cervical cancer cells. These results suggest that CTS can be used as a modulating agent in cervical cancer.

Most cervical cancers are caused by 15 high-risk (HR) and three probable high-risk (pHR) oncogenic types of human papillomavirus (HPV). However, current commercial HR HPV screening test products do not include pHR HPV genotypes. Recently, PapilloScreen has been developed to detect the 15 HR and three pHR HPV types. In this study, we evaluated the concordance levels and clinical performance of Hybrid Capture 2 (HC2), PapilloScreen, and a PCR sequencing assay in detecting HR and pHR HPV. The PapilloScreen (96.8 %) and PCR sequencing assay (96.8 %) demonstrated higher sensitivity than HC2 (80.7 %) for detecting HR and pHR HPV. The three assays showed similar specificities and positive or negative predictive values. The concordance levels were 86.5 % (κ = 0.68) and 86.5 % (κ = 0.67) between HC2 and PapilloScreen and between HC2 and PCR sequencing, respectively. A near-perfect concordance was observed between PapilloScreen and PCR sequencing (97.8 %, κ = 0.95). Overall, the agreement between the three assays suggests that the results obtained by the HC2 assay are more often discordant (12.6 %) than the PCR-based tests. In conclusion, PapilloScreen is highly sensitive for detecting high-grade CIN or cervical cancer. The PapilloScreen assay should be considered an accurate and sensitive method for detecting HR and pHR HPV infections and an epidemiological tool for prevalence studies as well as early diagnosis and intervention in HR and pHR HPV infections.

Background: The need for accurate genotyping of human papillomavirus (HPV) infections is becoming increasingly important as HPV is the primary cause of cervical cancer worldwide. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry-based restriction fragment mass polymorphism (RFMP) assay provides accurate, broad-spectrum, high-throughput genotyping of HPV., Objectives: We evaluated the clinical performance of the RFMP assay compared to a commercially available Roche linear array HPV genotyping test (LA) for detecting and genotyping of HPV., Study Design: The RFMP assay and the LA were compared for detecting and genotyping HPV among a cohort of 244 liquid-based cytology samples., Results: Overall, 216 specimens (93.1%, κ = 0.86) generated concordant results for the presence or absence of high-risk HPV (HR-HPV) by the two assays. The RFMP assay and the LA assay generated concordant, compatible, and discordant genotyping results for 79.3, 9.9, and 10.8%, respectively. The diagnostic sensitivity and specificity of RFMP and LA for the cervical lesions of squamous cell carcinoma (SCC) were similar, at 92.9 and 85.0% (RFMP) and 92.9 and 83.8% (LA), respectively. In addition, the odds ratio for SCC with HR-HPV positivity estimated by the RFMP assay (73.7, 95% CI: 8.9-3173.3) was higher than the LA assay (67.0, 95% CI: 8.2-2887.0)., Conclusions: The RFMP and the LA assays were highly comparable with regard to detection and genotyping analysis of HPV. The sensitivity and specificity of RFMP assay for the detection of HR-HPV in various levels of cervical lesions seems to be valuable in the monitoring of HPV-associated cervical cancer., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to develop a nomogram for predicting the 5-year disease-free survival (DFS) after radical hysterectomy for early-stage cervical cancer., Patients and Methods: An institutional database of 275 consecutive patients treated at Seoul National University Hospital for stage I to stage IIA cervical cancer was used to develop a nomogram based on Cox proportional hazards regression model. The developed nomogram was internally validated with bootstrapping, and performance was assessed by concordance index and a calibration curve. External validation was also performed using an independent data set of patients from Asan Medical Center., Results: From Cox regression analysis, disease stage, number of positive lymph nodes, parametrial involvement, and depth of invasion were identified as independent risk factors for disease recurrence (P < 0.05). The nomogram incorporating these factors appeared to be accurate and predicted the outcomes better than the International Federation of Gynecology and Obstetrics stage alone (concordance index, 0.858 compared with 0.719; P = 0.001). When applied to a separate validation set, the nomogram also showed similar predictive accuracy (concordance index, 0.879)., Conclusion: We have developed a nomogram that can predict the recurrence risk in patients with early-stage cervical cancer after surgery, which was internally and externally validated.

To evaluate the role of cyclooxygenase (COX)-2 during cervical carcinogenesis, we investigated COX-2 expression in the dysplastic epithelium and stromal cells of cervical intraepithelial neoplasia (CIN). Immunohistochemical analysis with COX-2 antibody was performed on 148 paraffin-embedded tissue specimens of patients who were diagnosed as CIN in our institute. COX-2 expression was evaluated separately in the dysplastic epithelium and stromal cells of CIN. The relationships between COX-2 expression and clinicopathologic variables were examined. For the dysplastic epithelium, COX-2 expression was negative in 137 (92.6%) and positive in 11 (7.4%) specimens. For the stromal cells, COX-2 expression was negative in all specimens. The COX-2 expression in dysplastic epithelium was higher in older (P= 0.038) or postmenopausal (P= 0.025) women. In conclusion, COX-2 expression was observed only in the dysplastic epithelium but not in the stromal cells of CIN. The COX-2 expression in dysplastic epithelium was associated with age and menopausal status.

Objective: The aim of this study was to investigate whether IL12B polymorphisms might be associated with increased risk and invasiveness of cervical cancer in Korean women., Study Design: Peripheral blood samples from patients with invasive cervical cancer (n=154) and non-cancer controls (n=191) were used to detect three biallelic IL12B polymorphisms at IVS2 -912, IVS4 +314, 3'UTR +1188 sites by performing SNaPshot assay. Allelic frequencies, genotype distributions, and haplotype patterns in the case group were compared with those in the control group. The relationships between these polymorphisms and cancer invasiveness were also evaluated by collating the clinicopathologic parameters including FIGO stage, lymph node status, histologic type, and parametrial invasion. The used analytic methods are chi-square test and logistic regression analysis., Results: Allelic frequencies of cases (G, 0.853; A, 0.147) were not significantly different from controls (G, 0.796; A, 0.204) in IVS2 -912G/A SNP (P=0.054). GG genotype of IVS2 -912G/A SNP showed increased risk for cervical cancer compared with AA genotype (P=0.040). The IVS2 -912G:IVS4+314A haplotype, IVS2 -912G:IVS4 +314A:3'UTR +1188A haplotype, and IVS2 -912G:IVS4 +314A:3'UTR +1188C haplotype were also significantly associated with increased risk for cervical cancer. A subgroup analysis of the clinicopathologic parameters in cancer group also showed that there is no significant association between IL12B polymorphisms and cervical cancer invasiveness., Conclusions: This study suggests that IVS2 -912GG genotype and IVS2 -912G:IVS4 +314A haplotype of IL12B gene are associated with increased risk for cervical cancer in Korean women.

Cervical cancer is a major health problem for Korean women, accounting for 9.8% of new female cancer cases, even though incidence rates have been decreasing. The Korean cervical cancer mortality rate for 1993-2002 based on National Statistical Office data shows an increasing trend, but the actual rates are thought to have decreased by epidemiologists, clinicians and other cancer experts. To explain this gap and solve this problem, we corrected the number of cervical cancer deaths by comparing death certificate cases of unspecified uterine cancer data with the national cancer incidence databases of entire cancer registries in Korea. We used 2 different methods to make a correction. First, we considered "uterus, unspecified" deaths previously registered as "cervix, uterine" cases misclassified and added them to the cervical cancer deaths. Alternatively, we multiplied the total number of registered unspecified uterine cancer deaths by age-specific proportions of registered incident cervical cancer cases among all cancers and added the product to cervical cancer deaths. The overall corrected age-standardized cervical cancer mortality rates per 100,000 women decreased from 5.2 in 1993 to 3.9 in 2002 (estimated annual percentage change (EAPC): -4.05%, 95% CI: -4.88, -3.22). While cervical cancer mortality showed a decreasing tendency in women aged 30-69 years, it increased substantially in women aged > or =70 years (EAPC: 3.62%, 95% CI: 1.92-5.35). Results of this study will provide evidence-based foundation for the evaluation of the existing cervical cancer-screening programs., (Copyright 2007 Wiley-Liss, Inc.)

We utilized three cervical cancer cell lines (HeLa, HT-3, and C33A) and clonogenic assays to determine whether cyclooxygenase (COX) expression is related to radiosensitivity. Using COX DNA transfection and COX inhibition by siRNA, we also examined changes in radiosensitivity caused by variations in COX expression. The survival fractions of HeLa and HT-3 cell lines, which both with COX-1 and COX-2 activity, were found to be significantly higher than that of the C33A cell line which had neither COX-1 nor COX-2 activity. Moreover, the acquisition of COX-1 in C33A cell line significantly reduced its radiosensitivity, but COX-2 transfection increased radiosensitivity in this cell line. In addition, the inhibition of COX-1 activity in HT-3 cell line using siRNA resulted in an increased radiosensitivity, but this phenomenon was not observed for COX-2 inhibition. The same experiment in HeLa cells using siRNA also showed no significant change in radiosensitivity. The results obtained during this study suggest that COX expression is associated with the radiosensitivity in uterine cervical cancer cell lines and COX-1 might have more important role than COX-2.

Aim: The aim of the present study was to evaluate the DNA hypermethylation profiles of 14 genes known to be associated with tumor behavior and their clinical significance in cervical cancer., Method: The clinical features of 82 patients with stage IB cervical cancer were analyzed in terms of DNA hypermethylation of 14 genes (hMLH1, p16, COX-2, CDH1, APC, DAPK, MGMT, p14, RASSF1A, RUNX3, TIMP3, FHIT, THBS1, and HLTF)., Results: Of 14 genes investigated, only hypermethylation of COX-2 showed significant association with poor disease-free survival (P = 0.001). To further investigate an alteration in COX-2 expression by DNA hypermethylation, immunohistochemistry for COX-2 protein was performed in the cervical cancer tissues. We found no significant association between hypermethylation and expression patterns of the COX-2 gene., Conclusions: The present results suggest that DNA hypermethylation of the COX-2 gene may be a potential prognostic marker in early stage cervical cancer, the underlying mechanism of which is independent of gene silencing.

Objective: To evaluate the diagnostic performance of magnetic resonance imaging (MRI) in the pretreatment evaluation of invasive cervical cancer especially for the parametrial invasion and lymph node (LN) involvement., Methods: We retrospectively recruited consecutive patients with biopsy-confirmed cervical cancer who had undergone preoperative MRI and were scheduled for surgery based on clinical assessment between January 2004 and May 2006. We evaluated the diagnostic performance of MRI for the parametrial invasion and LN involvement using surgicopathologic findings as the reference standard., Results: A total of 119 eligible patients completed preoperative and intra-operative survey, of whom 34 (28.6%) had pelvic LN metastasis and four (3.4%) had para-aortic LN metastasis histologically. The sensitivity, specificity and accuracy of MRI in detecting LN involvement by region-specific analysis were 40.5, 91.3 and 86.8% respectively. The sensitivity, specificity and accuracy of MRI in detecting parametrial invasion were 44.4, 89.1 and 88.3% respectively. The positive predictive value (PPV) of preoperative MRI for detecting region-specific LN involvement and parametrial invasion was 31.3 and 61.2%, respectively. Imaging findings of suspected parametrial invasion were not to influence the treatment decision in the study., Conclusion: Preoperative MRI showed low PPV for detecting LN involvement and parametrial invasion in cervical cancer. Further studies are necessary to determine the cost-effectiveness of using MRI in place of conventional clinical staging tests according to clinical indication and also its use in comparison with that of integrated positron emission tomography/computed tomography.

Objectives: To assess the value and clinical impact of integrated PET/CT using (18)F-FDG in the diagnosis and management of women with suspected cervical cancer recurrence., Methods: Fifty-two patients with cervical cancer with suspected recurrence because of clinical, cytological, biochemical and radiological findings were retrospectively evaluated. A final diagnosis of recurrence was confirmed by histologic tissue biopsy or by further clinical or radiological evidence. The clinical impact of information provided by PET/CT on patient management was assessed on the basis of clinical follow-up data concerning further diagnostic or therapeutic approach., Results: Twenty-eight of 32 positive PET/CT scans (87.5%) were proven to have recurrent disease. Seventeen of 20 negative PET/CT scans (85.0%) had no evidence of disease. The sensitivity, specificity, and accuracy of PET/CT for detecting recurrence were 90.3%, 81.0%, and 86.5% respectively. PET/CT changed the management of 12 patients (23.1%) by changing treatment plan (5 patients), by initiating unplanned treatment strategy (4 patients), or by obviating the need for planned diagnostic procedures (3 patients). Median duration after performing PET/CT and last follow-up was 12 (range: 6-27) months, and the 2-year disease-free survival rate of patients with negative PET/CT scan for recurrence was significantly better than that of patients with positive PET/CT (85.0% vs. 10.9%, P=0002)., Conclusions: In patients with a suspected recurrence of cervical cancer, integrated PET/CT using (18)F-FDG provides good anatomic and functional localization of suspicious lesions, and the better diagnostic interpretation has an impact not only on clinical management and treatment planning of patients, but also on disease-free survival.

Cervical cancer, the second most common malignancy in women worldwide, is almost invariably associated with infection by human papillomavirus (HPV). However, although many women are infected with high-risk types of HPV, only a subset of infected women will ever develop cervical cancer. Therefore, host genetic factor may play a role in cervical carcinogenesis. Alterations in epidermal growth factor receptor (EGFR) are common events in cervical cancer. Therefore, we hypothesized that a functional polymorphism in the 5' untranslated region of the epidermal growth factor (EGF) gene, a natural ligand of the EGFR, may play a role in the cervical carcinogenesis and tumor invasiveness. We assessed the possible association between EGF +61 A/G polymorphism and cervical cancer risk in a hospital-based case-control study among 337 Korean women (168 cases, 169 age-matched controls). The frequencies of EGF +61 allele and genotype were not different between cases and controls. We observed increasing trend of lymph node metastasis from A/A homozygous genotype toward G/G homozygous genotype. We did not find any evidence that EGF +61 A/G polymorphism was associated with individual susceptibility of cervical cancer. However, although it was not statistically significant, the increasing trend of lymph node metastasis according to EGF genotype suggests the possibility that individual variance of EGF expression may be associated with cervical cancer invasiveness. We also confirmed that there exists striking ethnic heterogeneity of EGF genotype between Caucasian and East Asian population.

Cervical cancer is almost invariably associated with infection by human papillomavirus. It is believed that the host genetic factors such as inflammation-induced cytokines may play a role in cervical carcinogenesis. The IL1B gene, encoding IL-1beta cytokine, contains several single nucleotide polymorphisms. One of them which is in the positions -511 (C-T) related with promoter region has been associated with increased IL-1beta production and with increased risk of developing a number of inflammatory diseases and gastric carcinoma. We assessed the association between the IL1B -511 polymorphism and cervical cancer risk in a hospital-based case-control study among 546 Korean women (182 cases; 364 age-matched controls). The allele frequencies of the case subjects (C, 0.42; T, 0.58) were not significantly different from those of control subjects (C, 0.43; T, 0.57). Control subjects were in Hardy-Weinberg equilibrium. The carriers with -511 C/T or T/T genotypes were at higher risk of cervical cancer with odds ratio of 2.42 (95% CI 1.31-4.46, p<0.005). However, there was no difference of cervical cancer risk between C/T heterologous genotypes and T/T homologous genotypes. In conclusion, in Korean population, IL1B -511 C/C genotypes were significantly associated with a decreased risk of cervical cancer.

Currently, many studies have shown that nitric oxide (NO) and prostaglandin (PG) are main inflammatory mediators involved in a variety of pathophysiological processes including inflammation and carcinogenesis. In this article, we explored the possible association of polymorphisms, of two representative inflammatory mediators, with the risk for cervical cancer. This study included 176 cases of histologically confirmed invasive cervical cancer, and 172 healthy controls. Allele frequency of 12 single-nucleotide polymorphisms (SNPs) of cyclooxygenase-2 (COX-2) and COX5 of the inducible nitric oxide synthase (iNOS) genes in 43 different normal populations were analyzed. We found that 14 of 17 showed a monomorphic or minimal minor allele frequency; therefore, we did not continue with additional analysis. Three SNPs (2 for COX-2, 1 for iNOS) were chosen for the study. Genotyping of three SNPs (SNP-rs5275 in the untranslated region of exon 10 and rs5277 in the coding region of exon 3 of COX-2, and iNOS Ser(608)Leu allele C/T polymorphism within exon 16 of the iNOS reductase domain) was performed. No significant increase was found in any of the genotypes of the COX-2 or iNOS in the cancer group. We investigated the possible correlation between the genotypes and the clinicopathologic parameters of cervical cancer. No significant association of the genotypes studied was found with respect to clinical stage, lymph node (LN) status, histologic type, or parametrial invasion. Our data did not reveal an association between COX-2 and iNOS polymorphisms with cervical cancer in Korean women.

Background: The purpose of this study was to determine the ovarian findings on integrated positron emission tomography/computed tomography scans during follow-up in cervical cancer patients with ovarian transposition., Method: We retrospectively reviewed the clinical data and integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography of women with ovarian transposition during radical hysterectomy for cervical cancer between December 2003 and March 2006., Results: Eighty-four premenopausal women had ovarian transposition performed during the study period. Twelve positron emission tomography/computed tomography scans from 11 patients were registered for the current study and three women were diagnosed with metastasis: two in lung and one in pelvis. Two patients complained of menopausal symptoms during follow-up, and the hormonal tests were consistent with it. In the current study, an integrated positron emission tomography/computed tomography scan detected one patient with right lower abdominal mass with increased 18F-fluorodeoxyglucose uptake, which was identified as a transposed right ovary. Clinical information of ovarian transposition was helpful in interpretation of the lesion. In the patient, transposed ovary was associated with increased fluorodeoxyglucose uptake, with standard uptake values ranging from 3.7 to 5.5. Other positron emission tomography/computed tomography scans did not show abnormal uptake of 18F-fluorodeoxyglucose., Conclusions: Transposed ovary in premenopausal women may appear on integrated positron emission tomography/computed tomography scan as a mass with increased 18F-fluorodeoxyglucose uptake, which may be associated with preserved ovarian function. Clinical information regarding transposition should be noted in order not to interpret these as recurrent or metastatic lesions.

Objective: To evaluate the potential benefit of postoperative radiotherapy (PORT) in women with isolated full-thickness cervical stromal invasion (FTSI) as an unfavorable pathological finding after radical hysterectomy and pelvic lymph node dissection (PLND) in FIGO stages IB-IIA cervical carcinoma., Methods: A total of 1868 patients with stages IB-IIA cervical carcinoma underwent radical hysterectomy and PLND between January 1982 and December 2002. Seventy-four of these patients had isolated FTSI without any other unfavorable pathological finding, such as lymph node metastasis, microscopic parametrial involvement, involved resection margin, lympho-vascular space invasion, or large clinical tumor diameter (>4 cm). Forty-one of these patients had no adjuvant treatment (S group) and 33 received PORT (PORT group). Patients with isolated FTSI who received chemotherapy were excluded. Treatment outcomes in the PORT and S groups were compared., Results: Ten-year disease-free survival (DFS) and pelvic-failure-free survival (PFFS) of S group vs. PORT group were 73.2% vs. 92.4% (P=0.038) and 79.8% vs. 97.0% (P=0.044), respectively. According to a Cox proportional hazards model developed by forward, stepwise regression incorporating all prognostic variables, only PORT was marginally significant for DFS (RR 0.234; 95% CI 0.051-1.067; P=0.061) and significant for PFFS (RR 0.055; 95% CI 0.005-0.620; P=0.019). A grade 4 late complication developed in two patients (6%) in PORT group., Conclusion: PORT administered to patients with isolated FTSI after radical hysterectomy and PLND improves pelvic control in FIGO stages IB-IIA cervical carcinoma with acceptable morbidity.

Cancer is primarily a disease of older adults. However, little data is available on the clinical features of cervical cancer in elderly patients. We investigated the trends in incidence and clinical features associated with cervical cancer among the elderly in Korea during the period of 1993-2002. We obtained data from the National Cervical Cancer Incidence Database, which was constructed in collaboration with the Korea Central Cancer Registry (KCCR) and Korea Gynecologic Cancer Registry (KGCR). A total of 44 191 women with cervical cancer were diagnosed between 1993 and 2002. Patients were divided into three groups based on age: /=70 years (Group 3). During this period, upward incidence trends were noted in Group 3 while constant and downward incidence trends were noted in Groups 1 and 2, respectively. Pooled analysis across years revealed that squamous cell carcinoma and advanced stage (IIB, III, and IV) were more common in Group 3 than in Groups 1 and 2. With regard to primary treatments in the elderly patients, surgery appeared to be performed increasingly despite the fact that advanced stage (IIB, III, and IV) was more common in Group 3 than in Groups 1 and 2. Our findings suggest that the incidence of cervical cancer in the elderly is increasing in Korea, while it is decreasing overall. The current health service must emphasize education for the elderly about cervical cancer prevention while concentrating on screening.

Objectives: To evaluate the toxicity and the efficacy of paclitaxel/carboplatin chemoradiotherapy as a definitive treatment for squamous cell cancer of the uterine cervix., Methods: From March 2000 to January 2004, 33 patients with squamous cell cancer of the uterine cervix were treated with concurrent chemoradiotherapy including 2 cycles of paclitaxel (135 mg/m(2)) and carboplatin (area under the time-concentration curve 4.5 mg min/ml) at 4-week interval. Seven patients received adjuvant chemotherapy with the same chemotherapeutic regimen. All patients received external beam radiotherapy with 41.4-51.4 Gy (median 50.4 Gy) to the whole pelvis. Twenty-eight patients received boost irradiation to the cervix by brachytherapy with 25.6-43.3 Gy (median 34.6 Gy) and 5 patients by external beam radiotherapy with 10.8-14.4 Gy (median 14.4 Gy)., Results: A median follow-up period was 27 months (range: 6-53 months). Acute hematological toxicity of grade 3 or 4 developed in 20 patients (61%), and acute gastrointestinal toxicity of grade 3 developed in 1 patient (3%). Vesicovaginal fistula occurred in 2 patients (6%). All patients achieved objective response (CR 70%, PR 30%) in 2 months after termination of treatment. One patient had a local progression in cervix, and 4 patients developed distant metastases. The 3-year estimated disease-free survival rates for stages I-IIA, IIB, III and IV were 67%, 91%, 88% and 50%, respectively. The 3-year estimated survival rates for stages I-IIA, IIB, III and IV were 89%, 91%, 88% and 50%, respectively., Conclusion: Concurrent chemoradiotherapy with paclitaxel and carboplatin is effective to achieve an excellent pelvic control.

Objectives: The aim of the study was to assess whether the genetic polymorphisms were associated with the tumor response in patients treated with platinum-based neoadjuvant chemotherapy (NAC) for bulky cervical cancer., Methods: We retrospectively reviewed the clinical data and recruited paraffin-embedded, formalin-fixed tissues of 36 patients with bulky cervical carcinoma. All patients underwent two or three cycles of platinum-based NAC followed by radical hysterectomy. We determined the genotypes of each single nucleotide polymorphism (SNP) of ERCC1, ERCC2, GGH, GSTP1, MTHFR, SLC19A1 and XRCC1 using single base primer extension assay., Results: The response to platinum-based NAC was higher in patients with SNP of XRCC1 R399Q (P=0.015), and there was a significant increased chance of treatment response in women with the G/G genotype (OR 38.0; 95% CI 1.66-870.45; P=0.023). The probability of response was also higher in patients with SNP of SLC19A1 6318C/T (P=0.032). There were dose-dependent influence of the number of alleles on the response to platinum-based chemotherapy (chi2 test for linear-by-linear association; P=0.009 for XRCC1 R399Q and P=0.017 for SLC19A1 6318C/T, respectively). Moreover, the multifactor dimensionality reduction (MDR) analysis documented that the combinations of XRCC1 R399Q and GGH-401C/T genetic polymorphisms were significantly associated with response to chemotherapy (P<0.0001)., Conclusions: Genetic polymorphism of XRCC1 R399Q is associated with response to platinum-based NAC in bulky cervical cancer, and MDR analysis documented association between gene-gene interaction of XRCC1 R399Q and treatment response.

This study was performed to determine whether promotor hypomethylation of CAGE is involved in cervical carcinogenesis. The surgical specimens of 40 cervical squamous cell carcinoma patients treated at Seoul National University Hospital and those of 48 healthy controls were used, with informed consent. We investigated the promotor hypomethylation status of CAGE by methylation-specific polymerase chain reaction (MSP) using primers specific for unmethylated sequences, and found hypomethylation of CAGE promotor at a frequency approaching 90% in cervical squamous cell carcinomas (35/40, 87.5%), but at less than 4% in controls (P < 0.001). This finding provides experimental evidence of the frequent hypomethylation of normally methylated CAGE promotor CpG islands in cervical cancer, and indicates that this hypomethylation is likely to be a valuable surrogate marker for the expression of CAGE. It also provides a clue concerning the molecular mechanisms of carcinogenesis in cervical squamous cell carcinoma.

This study examined the incidence rates, histologic and stage distribution, and long-term survival rates of patients with cervical cancer in Korea. A total of 44,182 patients diagnosed with cervical cancer between 1993 and 2002 were reported to the Korea Central Cancer Registry and the Gynecologic Oncology Committee of Korean Society of Obstetrics and Gynecology. The age-standardized incidence rates were 19.0, 17.8, and 15.1 per 100,000 women in 1993-1995, 1996-1998, and 1999-2002, respectively. The incidence rates of adenocarcinoma (AC) have been in the range between 1.2 in 1993-1995 and 1.4 in 1999-2002, while those of squamous cell carcinoma declined from 15.1 in 1993-1995 to 12.2 in 1999-2002. The 5-year relative survival rate was 79.2%. Relative survival rates, according to stage by the FIGO, at 5 years were 94.2%, 69.7%, 38.9%, and 21.1% for stages I, II, III, and IV respectively. Relative survivals improved between 1993 and 1997, probably due to the introduction of cervical cancer screening and effective treatment. The incidence rates of AC have been constant despite decreased cervical cancer in Korea. Introduction of cervical cancer screening and effective treatment may have contributed to the improved relative survival.

Objectives: To evaluate the efficacy of self-collected vaginal samples for high-risk HPV detection by the HPV oligonucleotide microarray method (HPVDNAChip)., Methods: One hundred and eighteen patients with abnormal Pap smears were included. Self-collected vaginal and clinician-collected cervical samples for HPV testing were obtained. The result of the HPV DNA test was compared with the histopathological diagnosis or colposcopic finding., Results: Of the 118 patients, 42 (35.6%) had >or= cervical intraepithelial neoplasia (CIN) III lesions. Using the HPVDNAChip, high-risk types of HPV were detected in 38 of these 42 patients (90.5%) with the self-collected vaginal samples and in 37 of 42 (88.1%) with the clinician-collected cervical samples. The agreement of HPVDNAchip results between self- and clinician-collected samples was very good (kappa = 0.81) with a 93.2% concordance rate. Multiple HPV infections were found in 17 of 88 (19.3%) HPV-positive clinician-collected cervical samples. The rate of multiple HPV infection tended to decrease as the degree of pathologic classification increased., Conclusion: Using the HPVDNAchip to assay for HPV infection, results from self-collected vaginal samples were compatible with those from clinician-collected cervical samples.

In a previous study, we demonstrated that elevation of COX-2 is significantly associated with lymph node metastasis in squamous cell carcinoma (SCC) of cervix. The main objective of this study is to characterize the relationship between elevation of COX-2 and its possible clinical role in adenocarcinoma (AC) of cervix. Using immunohistochemistry, we examined COX-2 expression levels in 84 patients with AC of uterine cervix [71 ACs, 13 adenosquamous carcinomas (ASCs)]. Elevation of COX-2 was correlated with clinicopathological variables and p53 expression, as detected by immunohistochemistry. Elevation of COX-2 was detected in 13.0% (11 of 84) of the tumors. Elevation of COX-2 was significantly correlated with histologic type (AC 8.5% vs. ASC 38.5%, P=0.011). Both tumor stage and lymph node metastasis were correlated with elevation of COX-2 with a borderline significance (P=0.062 and 0.068, respectively). Elevation of p53 was not associated with elevation of COX-2. The association between lymph node metastasis and elevation of COX-2 was stronger in cases of AC than in cases of ASC (28.4 vs. 4.3%, P=0.023). According to the results of univariate analysis, elevation of COX-2 was significantly associated with decreased overall survival (P=0.003, log-rank test). However, multivariate analyses revealed that only tumor stage was independently associated with overall survival, suggesting that elevation of COX-2 itself may not be an independent prognostic factor. The present study shows that elevation of COX-2 may contribute to lymph node metastasis in AC of uterine cervix. This suggests that the potential therapeutic role of COX-2 inhibitors should be validated, not only in SCC, but also in AC of uterine cervix.

Objective: To evaluate the efficacy and safety of concurrent chemoradiotherapy with paclitaxel and carboplatin after hysterectomy for early stage uterine cervical carcinoma with high risk factors., Methods: Between March 2000 and July 2002, 37 patients with stages IB-IIB uterine cervical carcinoma were treated with radical hysterectomy and bilateral pelvic lymph node dissection followed by concurrent chemoradiotherapy (POCCRT) with two courses of paclitaxel (135 mg/m(2)) and carboplatin (area under the time-concentration curve 4.5 mg min/ml) at 4-week interval. All the patients received external beam radiotherapy up to 50.4 Gy to the whole pelvis. Among these, 7 patients with close or involved resection margin received boost irradiation to the vaginal cuff (4 patients with low dose rate brachytherapy and 3 patients with external beam). Median dose of boost irradiation was 14.4 Gy (range: 14.4-34.6)., Results: Toxicity to POCCRT was mainly hematological and gastrointestinal, mostly grades 1 and 2. At a median follow-up of 27 months (range; 10-46), all the patients achieved local control, and 4 patients experienced distant relapses. The failure sites were as follows: bone (2 patients), paraaortic lymph node (1 patient), and supraclavicular lymph node (1 patient)., Conclusions: Concurrent chemoradiotherapy with paclitaxel and carboplatin after hysterectomy is well tolerated and produces excellent local control rate despite of short follow-up period. This regimen could be considered for a phase III trial.

The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite-modification technique and methylation-specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms., (2005 Wiley-Liss, Inc.)

In this study, we investigated the sequence variation and different transcriptional activities of the upstream regulatory region (URR) in HPV 16 E7 variants in cervical cancer tissue from Korean women. Using PCR-directed sequencing, the presence of sequence variations in URRs were analyzed and the sites of sequence variation were matched with the known transcriptional factor binding site (TFBS) in 26 HPV 16 E7 variants, 21 cases with A647G (KE7-1, high oncogenic potential) and 5 cases with T732C (KE7-2, low oncogenic potential). In addition, we determined the transcriptional activity of URR in a HPV 16 prototype, and in 4 cases of HPV 16 E7 variants, by using the functional chloramphenicol acetyl transferase (CAT) assay. The 26 HPV 16 E7 variants showed more than 11 sites of sequence variation in the URR. Ten sites of sequence variation were located in the known TFBS and the distribution of sequence variations in the URR showed clear differences between KE7-1 and KE7-2. The sequence variations T7781C and C7786T were matched with YY1 binding sites, G7193T and C7689A were matched with TEF1 binding sites, and C7394T and C7395T were matched with GRE binding sites. The other sequence variations, which were matched with the TFBS, were A7485C, G7489A, T7743G and G7842A. The URR activity of KE7-1 was significantly lower than that of the HPV 16 prototype, whilst KE7-2 was similar. Taken together with the results of the transcriptional activities of KE7-1 and KE7-2, our results suggest that the functional activity and sequence variations of HPV 16 URR may not be related to the oncogenic potential of HPV 16 E7 variants.

Though many investigators have reported relationships between the CCND1 polymorphism and susceptibility to various carcinomas, to our knowledge, no report has been issued concerning its relationship with uterine cervical cancer. Thus, we undertook this study to investigate the association between CCND1 polymorphisms and susceptibility to cervical cancer in Korean women. This study was carried on 222 patients with squamous cell carcinoma of uterine cervix and on 314 normal controls. CCND1 genotyping was determined by polymerase chain reaction and restriction fragment length polymorphism. The allelic frequencies of the cases (A, 0.53; G, 0.47) were not significantly different from those of the controls (A, 0.49; G, 0.51) (P=0.238). Regression analysis after adjusting for age showed that the CCND1 G870A genotypes are not related to the risk of squamous cell carcinoma of the uterine cervix. Our findings suggest that the CCND1 polymorphism is not associated with an increased risk of squamous cell carcinoma of uterine cervix in Korean women.

We examined whether Epstein-Barr virus (EBV) infection plays a role in cervical carcinogenesis in Korean women. EBV infection was examined using polymerase chain reaction (PCR) with two different primer pairs flanking the BamHI "W" fragment of EBV and by EBV-encoded small RNAs (EBER) in situ hybridization in various histologic types of cervical cancer, including 17 cases of squamous cell carcinoma, 36 cases of adenocarcinoma, and 3 cases of small-cell carcinoma. We also evaluated 20 cases of cervical intraepithelial neoplasia and 20 cases of normal uterine cervix. One case of squamous cell carcinoma and three cases of cervical intraepithelial neoplasia were positive for EBV DNA using PCR, but EBER in situ hybridization analysis showed that none of the PCR-positive cases expressed EBER. EBV DNA was not found using PCR in any of the 20 normal uterine cervices. From our results, EBV infection does not seem to play a role in cervical carcinogenesis in Korean women.

The aim of this investigation was to analyze the association between a single nucleotide polymorphism (SNP) in the matrix metalloproteinase (MMP)-1 promoter gene -1607 bp region and cervical cancer risk in Korean women. The blood samples of 232 cervical cancer patients and 332 non-cancer control subjects who managed at Seoul National University Hospital from 1999 to 2002 were collected. Polymorphism in MMP-1 promoter -1607 region was determined using TaqMan method. Allele frequency and genotype distribution in the cervical cancer group were compared with those of the control group to determine whether this polymorphism elevates the susceptibility of Korean women to cervical cancer. The relationship between this SNP and cancer invasiveness was also evaluated by collating clinicopathologic data of those in the cancer group, such as FIGO stage, lymph node status, histologic type and parametrial invasion. In the cervical cancer group, the allele frequency of 2G was 66.1%, in the control group 68.2%, showing no significant difference (P=0.41). Similarly the genotypes with insertion (2G/2G) or deletion (1G/1G) polymorphism showed no increased risk for cervical cancer susceptibility compared with 1G/2G genotype. A subgroup analysis of the clinicopathologic parameters in cancer group also showed no significant difference suggesting the lack of an association between SNP of the MMP-1 promoter -1607 bp region and cervical cancer invasiveness. In conclusion, this study shows that Korean with specific polymorphism in MMP-1 are neither more susceptible to develop cervical cancer nor more vulnerable for cancer progression.

The aim of this study was to identify sequence variants in the HPV 16 E6 gene in Korean women and to examine the possible association between these sequence variants and cervical cancer development. We examined the HPV 16 DNA of 215 patients with no cervical disease (NCD) (n = 105) or with cervical neoplasia (n = 110) [cervical intraepithelial neoplasia (CIN), n = 61; invasive cervical carcinoma (ICC), n = 49] using the nested polymerase chain reaction (PCR) and PCR-directed sequencing methods. Fifty-four (NCD, n = 10; CIN, n = 17; ICC, n = 27) of the 215 samples contained HPV 16 E6 DNA, but only two (7.4%) of 27 ICC samples had prototype sequences. The most frequently found variation was D25E (in NCD, n = 8, 80%; in CIN, n = 9, 52.9%; in ICC, n = 23, 85.2%). This is a rare variation in western countries. No significance difference was found between the frequencies of D25E variation in cancerous and non-cancerous lesions. Among the 11 kinds of variants identified, four variants were novel and have been registered with GenBank. This study demonstrates that the D25 variant is the most prevalent E6 genomic variant type in Korean population. However, it was not found to be associated with an increased risk of ICC.

To evaluate the tolerance and the outcome of radical surgery in the management of elderly patients with uterine cervical cancer in Korea, seventy-seven patients with stage Ib or IIa squamous cell carcinoma of the uterine cervix, diagnosed at Seoul National University Hospital from January 1996 to June 2003, were retrospectively reviewed. Sixty-six patients undergoing radical surgery were divided into two groups according to their age: 41-50 years (group A; n = 43) and 65 years or older (group B; n = 23). Statistical analysis was conducted by using Mann-Whitney U test and Fisher's exact t test. Although group B consists of more stage IIa cases than group A (27.9 vs. 52.2%), the difference in the stage between both groups was statistically insignificant. Medical comorbidities in group B were higher than group A, primarily due to hypertension (23.3 vs. 56.5%, p = 0.014). Mean operation time, mean blood loss, perioperative transfusion, frequency of intraoperative injuries, duration of hospital stay, and postoperative complications were similar except 1 case of operation-related mortality in group B. The pathologist's report indicated a positive resection margin of the vagina in 6 cases of group B but none in group A. The difference in parametrial involvement, lymph node involvement, lymphovascular space invasion, deep cervical wall involvement and larger tumor with a diameter >4 cm was not significant. The number of patients who received adjuvant therapy was significantly higher in group B than group A (23.3 vs. 65.2%, p = 0.001). The recurrence rate, however, was not different. Our study suggests that radical surgery in the management of elderly patients with stage Ib or IIa uterine cervical cancer is reasonably feasible. Chronological age alone should not be considered a contraindication to radical hysterectomy., (Copyright (c) 2005 S. Karger AG, Basel.)

Objective: This study was conducted to explore the association between the CpG island hypermethylation of tumor-associated genes and the polymorphisms of methyl group metabolizing enzymes in uterine cervical cancer., Methods: We analyzed CpG island hypermethylation in 15 genes (APC, CDH1, COX2, DAPK, FHIT, GSTP1, HLTF1, hMLH1, MGMT, p14, p16, RASSF1A, RUNX3, THBS1, and TIMP3) and its association with the methylene-tetrahydrofolate reductase (MTHFR) C677T and A1298C and the methionine synthase (MS) A2756G polymorphisms in 82 Korean women with uterine cervical cancer., Results: All uterine cervical cancer samples had at least one gene methylated. The average number of methylated genes was lower in patients with the heterozygous genotype of MTHFR and MS than in those with the common homozygous genotype, although this difference was not significant. The MTHFR 677 CT genotype was significantly associated with the decreased promoter hypermethylation of O(6)-methylguanine DNA methyltransferase (MGMT) (OR = 0.22, 95% confidence interval (CI) 0.07-0.70, P = 0.011). However, the MTHFR C677T and A1298C and the MS A2756G polymorphisms were not associated with an increased risk of uterine cervical cancer., Conclusion: These findings suggest that there is a possible interaction between epigenetic and genetic factors in uterine cervical cancer.

This study determined the distribution of high-risk HPV type infection in cervical cancer using newly developed oligonucleotide chips (HPVDNAChips). The study subjects included 80 cases of cervical neoplasia and 746 controls with a normal Pap smear. For HPV genotyping, the commercially available HPVDNAChips was used. The risk of cervical cancer was increased in women with a family history of cervical cancer (adjusted OR=2.3, 95% CI: 0.92-6.17) and in smokers (adjusted OR=3.2, 95% CI: 1.45-7.06). There was also a trend of increased risk with the number of full term pregnancies (P(for trend)<0.001). There were only 7.2% (54 of 746) infected high-risk HPV types in the control, whereas 54.5% (six of 11) and 76.5% (52 of 68) were infected in the CIN and cervical cancer, respectively. Multiple HPV infection was observed in 0.5% (three of 592) of the control group but in 9.1% (seven of 77) of cases. Multivariate analysis revealed that subjects infected with multiple HPV types had a 31.8-fold (95% CI: 7.50-134.75) higher risk of cervical cancer, while the single HPV type had a 19.9-fold increased risk (95% CI: 10.90-36.18) (P(for trend)<0.001). These results show that the detection and typing of HPV infection by HPVDNAChip can be a useful in clinical applications because it provides information on multiple infections and the types of HPV in addition to HPV infection status.

Objectives: This study examines the relationship between expression of COX-1, COX-2, and vascular endothelial growth factor (VEGF), and their association with clinicopathological features in primary tumor and metastatic lymph node specimens from cervical cancer patients. The relationship between COX-2 expression and human papillomavirus (HPV) positivity was also examined., Methods: The following samples were analyzed: 97 paraffin-embedded specimens from patients with cervical cancer (Ib-IIb), including 49 primary cervical cancer specimens without lymph node metastasis and 24 primary specimens with lymph node metastasis and their metastatic lymph nodes. Immunohistochemical analysis was performed with antibodies to COX-1, COX-2, and VEGF. HPV viratype was identified by PCR and HPVDNAChip., Results: VEGF expression was strongly correlated with expression of COX-1 (P = 0.03) and not COX-2 (P = 0.12) in primary tumor and metastatic lymph nodes. COX-2 expression correlated with lymph node metastasis (P = 0.001), but not with any other clinicopathological features. The parametrial invasion showed borderline significance with COX-2 expression (P = 0.058). COX-1 or VEGF expression did not correlate with any clinicopathological features. In addition, COX-2 expression was not associated with HPV positivity.COX-1 expression is associated with VEGF expression in primary tumor tissue and at sites of metastasis to lymph nodes., Conclusion: COX-2 expression is associated with lymph node metastasis and possibly parametrial invasion, but expression of COX-1 and VEGF is not associated with clinicopathological features. COX-2 expression is not associated with HPV positivity.

Objective: The aim of this study was to describe the cervical cancer survival rates in Singapore during the period of 1968 through 1992 using population-based data., Study Design: A review of cases with cervical cancer diagnosed between 1968 and 1992 from Singapore Cancer Registry was conducted. Information on vital status at December 31, 1997, was available for 3531 cases. Cumulative observed and relative survival rates were computed by using Hakulinen's method., Results: Survival in cervical cancer in Singapore has improved over the 25-year period. The overall 5-year age-standardized relative survival (ASRS) for all patients increased from 45% in 1968-1972 to 65% in 1988-92. Poorer survival rates were observed in elderly patients and Malays., Conclusion: The improvement in survival of cervical cancer is likely to be attributed to the rapid national development of Singapore, resulting in the improvements in health services infrastructure and accessibility, as well as to the impact of widely available cytology-based screening resulting in early detection.

The aim of this study was to estimate whether the Ile184Arg polymorphism of the Interferon, alpha 17 (IFNA17) gene might be correlated with the risk and prognosis of cervical squamous cell carcinoma (SCCA). Genomic DNA from 173 patients with invasive cervical SCCA and from 198 non-cancer controls (NCC) was examined for the Ile184Arg polymorphism with a polymerase chain reaction-restriction fragment length polymorphism-based assay. All P values are from two-sided tests. The distribution of IFNA17 Ile184Arg genotype among SCCA cases (Ile/Ile, 21%; Arg/Ile, 57%; and Arg/Arg, 22%) was different significantly from that among NCC (Ile/Ile, 32%; Arg/Ile, 56%; and Arg/Arg, 12%) (P=0.0345). A significant increase in 184Ile homozygote frequency was found in the SCCA patients compared with the NCC group (odds ratio 2.96; 95% confidence interval 1.53-5.73; P=0.001). However, differences in clinicopathologic prognostic factors and in the 5 year survival rate were not significant among the subjects of each genotype group (P>0.05). The results of this study suggest that the 184Ile homozygote of the IFNA17 gene may represent an important susceptibility biomarker for cervical cancer risk.

Although cytologic screening has considerably reduced the incidence of cervical cancer, there are some problems which remain to be solved, such as the low sensitivity of this procedure. HPV testing is fundamentally different from conventional cytologic testing, because it evaluates the HPV infection itself, the most important causative factor for cervical cancer. In this study, the roles and clinical applications of HPV testing in cervical cancer screening are examined from 3 standpoints: in primary screening, in the management of women with low-grade cytologic abnormalities, and in the follow-up after treatment of pre-invasive or early invasive lesions.

The aims of this study were to determine whether polymorphisms of the interleukin (IL)-10 promoter might be associated with an increased risk of cervical cancer, and further whether systemic IL-10 concentration might be influenced by the genotypes in Korean women. Peripheral blood samples from patients with invasive cervical cancer (ICC, n=144) and non-cancer controls (NCC, n=179) were used to detect three biallelic IL-10 promoter polymorphisms at -1082, -819, and -592 sites by polymerase chain reaction-restriction fragment length polymorphism assay using MnlI, MaeIII and RsaI, respectively. The IL-10 serum concentration was measured with enzyme-linked immunosorbent assay. We compared the distribution of genotypes in both groups, evaluated the serum IL-10 level according to the genotypes, and analyzed the association of these polymorphisms with the risk of cervical cancer. The genotype at the -1082 site exhibited only the *A homozygote, and only two haplotypes were found in Korean women, one being -1082*A/-819*T/-592*A (ATA) and the other -1082*A/-819*C/-592*C (ACC). No association was found for IL-10 promoter polymorphisms among the ICC patients in comparison with the NCC subjects. The risk of cervical cancer was not increased in either genotype and the IL-10 serum concentration was not influenced by the genotypes in either group. Polymorphisms of the IL-10 promoter do not appear to be associated with cervical cancer risk or systemic IL-10 production in Korean women.

The technique of large loop excision of the transformation zone (LLETZ) came into vogue in the 1990s, and has been widely used in place of cold knife conization for diagnosis and treatment. Although its therapeutic efficacy for cervical intraepithelial neoplasia (CIN) has been confirmed and accepted in many countries, no direct comparison is available of the efficacies of LLETZ and hysterectomy for the treatment of CIN III, and unfortunately, hysterectomy is still widely used in many other countries. The aim of this analysis was to confirm the efficacy of LLETZ for the treatment of CIN III and to compare its results with those of hysterectomy. Between Jan. 1993 and Dec. 1997, 380 patients with CIN III were treated in the Seoul National University Hospital. We defined group I (n = 101) as those patients who underwent therapeutic LLETZ and follow-up only and group II (n = 279) as those patients who underwent hysterectomy following LLETZ. Three patients in groups I (3.0%) and II (1.1%) developed persistent/recurrent CIN or vaginal intraepithelial neoplasia (VAIN). This result was not statistically significant. Group II contained more patients with positive resection margins and glandular extensions than group I (P < 0.05), and these factors might have been confounding variables. However, when parameters influencing the rate of treatment failure were compared, no significant differences were found by logistic regression analysis (P > 0.05). The results obtained show that the LLETZ is almost identical in terms of its therapeutic efficacy to hysterectomy and that it should be accepted as a standard treatment for CIN III.

Objective: To confirm that the ThinPrep Pap test (TP) is as effective as or more effective than the conventional Papanicolaou smear (CS) in detecting epithelial cell abnormalities in a population with cervical abnormalities., Study Design: In a blinded, split-sample, matched-pair study, a CS was prepared using a cytobrush, and then TP slides were prepared from the remainder of the sample. All slides were evaluated as defined and classified by the Bethesda System. The results of the two cytologic tests were compared in 483 women relative to the histologic diagnoses of subsequent colposcopically directed cervical biopsies in 158 cases., Results: The cytologic diagnoses from the two methods agreed exactly in 91.4% of cases. The comparison between the two cytologic diagnoses with reference to the histologic diagnosis of subsequent colposcopically directed cervical biopsies showed that TP was significantly more specific for diagnosing lesions than was CS. The sensitivity of the two methods was equivalent., Conclusion: In a population with cervical abnormalities, TP is more specific than and as effective as CS in detecting cervical epithelial cell abnormalities. TP improved the specificity of disease detection by reducing the atypical squamous cells of undetermined significance category and/or false positive cases.

Objective: It has recently been suggested that white women who are homozygous for the allele of the gene for wild-type p53 protein (TP53) that encodes arginine at position 72 are more susceptible to human papillomavirus-associated cervical carcinoma than are women who are heterozygous for this polymorphism and women who are homozygous for the allele that encodes proline at that position. This study was undertaken to analyze whether the TP53 codon 72 single-nucleotide polymorphism might be correlated with the risk of cervical cancer among Korean women., Study Design: Peripheral blood samples from patients with invasive cervical carcinoma yielding a positive result for human papillomavirus 16 (n = 100), patients with cervical intraepithelial neoplasia grade III (n = 134), and healthy control subjects (n = 100) were examined. The presence and genotype of human papillomavirus in cancerous cervical tissues were determined by E6, E7-based nested polymerase chain reaction. Germline genomic deoxyribonucleic acid was extracted from peripheral blood leukocytes and examined by polymerase chain reaction amplification of the specific allele assay as described by Storey et al. Deoxyribonucleic acid samples from patients whose TP53 sequences had been determined by direct sequencing were used as positive control preparations., Results: The respective proportions of individuals who are homozygous for the arginine allele, homozygous for the proline allele, and heterozygous for the 2 alleles were 40%, 12%, and 48% among women with invasive cervical carcinoma, 52%, 9%, and 39% among women with cervical intraepithelial neoplasia grade III, and 52%, 11%, and 37% among the control group. No significant differences in the frequency of codon 72 alleles were found among the 3 groups (chi(2) = 4.414; P =.353; degrees of freedom = 4)., Conclusion: This finding suggests that the risk of cervical cancer may not be increased for Korean women with the allele of TP53 encoding arginine at codon 72.

Objective: A hospital-based case-control study was conducted to identify characteristics of women at high risk of developing cervical cancer with special reference to sexual behavior in Korea., Methods: Histologically confirmed cases of invasive cervical cancer were selected from the Department of Gynecology, Seoul National University Hospital between September 1992 to May 1995 (n = 203). Women with normal pap smear tests and women free of past history of any malignancies were regarded as controls (n = 827). Information on risk factors were collected by both a self-administered questionnaire and a direct interview., Results: Uterine cervical cancer risk was higher in women with a less educated spouse (Ptrend = 0.0003), women with a family history of cervical cancer (adjusted odds ratio [OR] = 2.20., 95% confidence interval [CI] 1.21-4.01), women of shorter height (Ptrend = 0.02), women with early age at first full term pregnancy (Ptrend = 0.0005), and women who have had multiple full term pregnancies (Ptrend = 0.006) by the multiple linear logistic analysis. Particularly noteworthy was a significant decreasing trend in the adjusted OR with the age at first sexual intercourse increasing (Ptrend = 0.002) after adjusting the number of sexual partners. The husband's indecent sexual history showed a borderline significance (Ptrend = 0.07)., Conclusions: This study confirmed that the risk factors of cervical cancer in Korea are similar with those found in other countries.

Geographic specificity of nucleotide sequence variations in the coding and noncoding regions of HPV 16 genome has been reported. Little has been known, however, regarding whether these naturally occurring sequence variations of HPV 16 may result in marked differences in biological properties, such as oncogenic potential. This study was performed to identify sequence variants in the HPV 16 E7 gene derived from Korean women with cervical cancerous and noncancerous lesions, and to assess the association between the sequence variant and the cervical cancer. We examined E7 variants of HPV 16 in a total of 157 patients with no cervical disease (NCD, n = 87) or cervical neoplasia (cervical intraepithelial neoplasia 3, n = 21; cervical carcinoma, n = 49), using the nested polymerase chain reaction (PCR) and the PCR-directed sequencing methods with outer consensus and inner type-specific primers. Forty-two (NCD, n = 9; CIN 3, n = 6; cervical carcinoma, n = 27) of 157 cervical samples contained HPV 16 E7 DNA, but only 8 had prototype sequences. Four variants of the HPV 16 E7 gene were identified. The variant with a single nucleotide change at position 647 (A --> G, Asn --> Ser) was found in about 60% of DNA samples with HPV 16. The second most common variant, found in 16.7% of cases, had three silent mutations at positions 732 (T --> C), 789 (T --> C), and 795 (T --> G). Two other variants were detected, one in a patient with cervical cancer and the other in a patient with no cervical disease. One had a single nucleotide change at position 666 (G --> A) and the other had one silent mutation at position 796 (T --> C). The most common variant in Korea has a change of nucleotide affecting the predicted amino acid related with high antigenicity and binding to retinoblastoma protein. There was a statistically significant trend for this variant to be more frequently detected in cancerous lesions of the uterine cervix than in noncancerous lesions. These data suggest that naturally occurring sequence variants of HPV 16 E7 gene may have different oncogenic properties.

Background: The investigation of cervical cancer screening acceptance in relation to health beliefs and attitudes presents a challenge in a multiethnic population such as Singapore's, where the uptake is currently suboptimal in high-risk groups. This study attempts to identify cognitive barriers to screening activity in order to suggest possible directions for cervical cancer prevention efforts., Methods: A cross-sectional survey consisting of a household interview of 640 randomly selected women ages 21-65 years was performed. The screening history and future intention to have a Pap smear were elicited, and attitudes toward cancer and the Pap smear as expressed in 14 statements were measured on a five-point scale., Results: Of the respondents, 73.1% were aware of the Pap smear, and about half (49.7%) had obtained the information from a doctor or nurse. Overall, the belief in personal susceptibility to cancer was low (58.9%) and a substantial proportion (48.7%) of women were of the attitude that cancer could not be prevented. The effect on a future intention to have a smear varied between women who had had and women who had not had a smear. Among the former, perceived barriers such as discomfort and embarrassment had a significant influence, while a belief in personal susceptibility was an important determinant for the latter group., Conclusions: The means of increasing the acceptance of the Pap smear, both for the first time and subsequently, are culture-specific and must address the appropriate health beliefs and attitudes. In Singapore, such efforts should include not only influencing awareness and perceptions through public education but also reducing barriers by creating an appropriate environment for the delivery of this important health service.

Purpose: Pelvic radiation is standard treatment for women with stage IIb to IVa cervical cancer, but treatment results are disappointing, particularly for women with bulky tumors. We investigated the role of primary chemotherapy followed by pelvic radiotherapy in a randomized trial., Patients and Methods: Two hundred sixty patients with stage IIb and IVa cervical cancer received either standard pelvic radiotherapy or primary chemotherapy with cisplatin 60 mg/m2 and epirubicin 110 mg/m2 administered at 3-week intervals for three cycles, followed by pelvic radiotherapy., Results: Ninety-nine patients have relapsed with a median follow-up duration of 1.3 years; in 62 patients, the first site of progressive disease was the pelvis. Patients who received primary chemotherapy had a significantly higher pelvic failure rate than those who received radiotherapy alone (P < .003). Seventy-six patients have died, and those who received primary chemotherapy had significantly inferior survival compared with those who received radiotherapy alone (P = .02). Tumor response following chemotherapy was observed in 63%. After radiotherapy, tumor response occurred in 72% of those who received combined modality treatment, compared with 92% of those who received radiotherapy alone., Conclusion: Primary chemotherapy with epirubicin and cisplatin, although resulting in tumor response in a significant proportion of patients, is accompanied by an inferior local control rate and survival compared with standard pelvic radiotherapy alone.

A cross-sectional survey of 568 married women aged 21-65 years in the Pasir Panjang Constituency was conducted to determine the prevalence of cervical cancer screening in the community and the factors affecting acceptance of this screening test. Results show that 309 (54.4%) of the respondents had ever had a Pap smear. The women who reported having had a smear were more likely to be below 45 years of age (prevalence ratio 1.47, 95% confidence interval 1.15 to 1.88), Chinese and of a higher socioeconomic status (1.68, 1.33 to 2.12). They were also more likely to have married at a later age (1.68, 1.21 to 2.31) than women who had not had a smear. Age and socioeconomic status remained independent predictors on multivariate analysis. The findings suggest that an important task of public health practitioners is to increase the uptake of screening among older and socially disadvantaged women who are known to be at the highest risk of cervical cancer. In addition, strategies to encourage younger women to continue regular attendance at screening clinics beyond their childbearing years will be important for the future.

Objective: The aim of this study was to compare CT and MRI at 0.5 T in the preoperative staging of uterine cervical cancer in a large series of patients., Materials and Methods: Ninety-nine patients with uterine cervical carcinoma underwent CT, MRI, and surgical exploration., Results: Both CT and MR findings were compared using surgical-pathologic findings as gold standards. Magnetic resonance imaging was superior to CT in tumor detection (sensitivity 75 vs. 51%, p < 0.005), in parametrial evaluation (accuracy 87 vs. 80%, p < 0.005), in overall tumor staging (accuracy 77 vs. 69%, p < 0.025), and in pelvic lymph node evaluation (accuracy 88 vs. 83%, p < 0.01). Magnetic resonance imaging had an accuracy of 76% in assessment of the thickness of cervical stromal invasion., Conclusion: Magnetic resonance imaging was superior to CT in preoperative staging of uterine cervical carcinoma and MRI should be used instead of CT for preoperative staging of this disease.

Analysis of data collected by the population-based Singapore Cancer Registry reveals that the age-standardised incidence of cervical cancer has decreased from 18.2 per 100,000 females in 1968-72 to 16.2 per 100,000 in 1983-87, and its ranking among the most common female cancers has fallen from second to fourth place behind cancers of the breast, colon/rectum and lung. Mortality from the disease has also shown a corresponding fall from 7.3 per 100,000 to 5.5 per 100,000 women over the same period. Cervical cancer incidence rates are in general highest among Indian women, intermediate in Chinese and lowest in Malays. Age-specific incidence curves over time show a marked fall in rates in women over 50 years of age, whereas younger women (35-44 years old) show a small increase. A similar increase in rates has been observed in various other countries. Internationally, Singapore's incidence rate falls between the highs of South America and parts of Asia, and the lower rates of North America and Europe. The decrease in rates is comparable with the overall global trend, but falls short of that achieved by countries with systematic cytological screening programmes.

Thirty patients with uterine cervical carcinoma underwent computed tomography (CT), magnetic resonance (MR) imaging, and surgical exploration. MR imaging was superior to CT in visualization of the tumor. MR imaging had an accuracy of 77% in the assessment of thickness of cervical stromal invasion. The accuracy rates of these modalities for parametrial evaluation were 78% for clinical evaluation, 70% for CT, and 92% for MR imaging. The overall accuracy rates for tumor staging were 70% for clinical evaluation, 63% for CT, and 83% for MR imaging. MR imaging is superior to clinical evaluation and CT in parametrial evaluation and the staging of uterine cervical carcinoma.

Cervical cancer, despite its declining incidence in the developed countries, is still an important cancer in the less-developed world. The mortality and incidence trends for some of the countries in the Pacific Basin are presented. Among the high-risk communities and populations are Colombia (Cali), New Zealand (Maoris), El Paso, Texas (Latin Americans), California (blacks), Hawaii (Hawaiians), Singapore (Chinese and Indians), Hong Kong, Philippines (Manila), New Caledonia (Melanesians), Alaska (American Indians), Fiji. The major risk factors are summarized, with age at first coitus as the key factor; some doubts are expressed about the validity of multiple sexual partners and circumcision of male partners as risk factors. The likely role of herpesvirus is still being studied, and the possible increase in incidence of cervical cancer among younger women could be attributed to greater sexual promiscuity in that group. Some suggestions for future research are made.