• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.305-308
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• 2014

Background: To investigate the indications of loop electrosurgical excision procedure (LEEP) and its overtreatment rates for the see and treat and three step strategies in cases of atypical squamous cells of undetermined cytology (ASC-US) and low grade intraepithelial neoplasia (LGSIL) cytology. Materials and Methods: We retrospectively analyzed colposcopy directed biopsy (CDB) and LEEP results of 176 paients with ASC-US or LGSIL cytologies who underwent colposcopic examination. Results: Initial cytologies were ASCUS in 120 women and LGSIL in 56. According to the see and treat approach immediate LEEP was performed for38 women. Among the remaining 138 women, LEEP was performed for 32 whose CDB results revealed CIN2/3 lesions. In the see and treat group the recognition of CIN2/3 was found to be 39.4%. The overtreatment rate was 60% as compared to 25% in the three step group. In CDB group detection of CIN 2 or greater lesions increased with 3 or more biopsies. Conclusions: In patients with ASC-US/LGSIL cytologies CDB should be performed before LEEP to prevent overtreatment, with attention to all suspected areas and more than 2 biopsies taken.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6005-6008
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• 2014

Aim: To compare recurrence rates of large loop excision of the transformation zone (LLETZ) with those of contour-loop excision of the transformation zone (C-LETZ) in the management of cervical intraepithelial neoplasia (CIN). Materials and Methods: The medical records of 177 patients treated consecutively by LLETZ and C-LETZ for CIN at Rajavithi Hospital between 2006 and 2009 were retrospectively reviewed. Results: Of the 87 women in the C-LETZ group, 2 cases (2.30%) had recurrence compared with 13 cases (14.4%) of the 90 women in the LLETZ group, the higher recurrence rate in the latter being statistically significant (p<0.05). Median times of follow up in the C-LETZ and LLETZ groups were 12 months and 14 months respectively (p>0.05). The C-LETZ group showed less intraoperative bleeding compared to the LLETZ group, but the rate of achievement of single specimens and positive margins were similar in the two groups. Conclusions: The present study demonstrated the superiority of C-LETZ over LLETZ in terms of efficacy; C-LLETZ is associated with a lower recurrence rate and also carries a smaller risk of intraoperative bleeding than LLETZ. The rotating technique still has a potential role in treating precancerous lesions of the cervix.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9679-9685
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• 2014

Background: When evaluating health-economics for cervical cancer prevention policies in Japan, it is important to use Japanese value settings. This study aimed to obtain preference-based measures (preference measures) for hypothesized health states among healthy Japanese women, and to examine differences between the EuroQol-5D (EQ-5D) and standard gamble (SG) instruments. Materials and Methods: The investigation was performed among female students at a nursing university. We used written hypothetical scenarios describing three grades of cervical intraepithelial neoplasia (CIN) and eight stages of cervical cancer, both at diagnosis and after medical intervention. Preference measures were evaluated using both EQ-5D and SG. Results: We received responses from 136 women. The mean number of respondents per stage was 24.6 (SD: 2.7). At diagnosis, average EQ-5D scores for CIN1, CIN2, CIN3, IA1, IA2, IB1, IB2, IIA, IIB, III, and IV stages were 0.84 (0.14), 0.78 (0.12), 0.73 (0.10), 0.78 (0.12), 0.72 (0.12), 0.63 (0.13), 0.64 (0.12), 0.68 (0.08), 0.62 (0.13), 0.55 (0.21), and 0.18 (0.24), respectively. Using one-way analysis of variance with the Tukey-Kramer method for multiple comparisons (each stage vs. CIN1), we found significant differences for IB1 and more advanced stages (p<0.05). After medical intervention, corresponding EQ-5D scores were 0.84 (0.12), 0.81 (0.12), 0.84 (0.12), 0.80 (0.15), 0.78 (0.11), 0.64 (0.15), 0.63 (0.15), 0.71 (0.15), 0.50 (0.17), 0.52 (0.17), 0.21 (0.28). The multiple comparisons identified significant differences for IB1 and more advanced stages, excepting IIA (p<0.05). SG evaluations were more variable and relatively higher than EQ-5D evaluations. Conclusions: We obtained preference measures for three grades of CIN1-3 and eight stages of cervical cancer. In combination with appropriate sensitivity analyses, these preference measures will provide a basis for an economic evaluation of cervical cancer prevention in Japan. We suggest that EQ-5D is appropriate for cost-utility analysis of this topic.

• The Korean Journal of Cytopathology
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• v.19 no.2
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• pp.111-118
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• 2008

Background : Cervicovaginal cytology is a screening test of uterine cervical cancer. The sensitivity of cervicovaginal cytology is less than 50%, but studies of cytologic/histologic correlation are limited. We analyzed the diagnostic accuracy of cervicovaginal cytology in the detection of the squamous epithelial lesions of the uterine cervix and investigate the cause of diagnostic discordance. Materials and Methods : We collected a total of 481 sets of cervicovaginal cytology and biopsies over 5 years. The cytologic diagnoses were categorized based on The Bethesda System and the histologic diagnoses were classified as negative, flat condyloma, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, or squamous cell carcinoma. Cytohistologic discrepancies were reviewed. Results: The concordance rate between the cytological and the histological diagnosis was 79.0%. The sensitivity and specificity of cervicovaginal cytology were 80.6% and 92.6%, respectively. Its positive predictive value and negative predictive value were 93.7% and 77.7%, respectively. The false negative rate was 19.4%. Among 54 false negative cytology cases, they were confirmed by histology as 50 flat condylomas, 2 CIN I, 1 CIN III, and 1 squamous cell carcinoma. The causes of false negative cytology were sampling errors in 75.6% and interpretation errors in 24.4%. The false positive rate was 7.4%. Among 15 false positive cytology cases, they were confirmed by histology as 12 atypical squamous cells of undetermined significance (ASCUS) and 3 low grade squamous intraepithelial lesions (LSIL). The cause of error was interpretation error in all cases. The overall diagnostic accuracy of cervicovaginal cytology was 85.7%. Conclusions : Cervicovaginal cytology shows high overall diagnostic accuracy and is a useful primary screen of uterine cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9313-9317
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• 2014

Fragile histidine triad (FHIT) is a suppressor gene related to cervical cancer through CpG island hypermethylation. Folate is a water-soluble B-vitamin and an important cofactor in one-carbon metabolism. It may play an essential role in cervical lesions through effects on DNA methylation. The purpose of this study was to observe effects of folate and FHIT methylation and HPV 16 on cervical cancer progression. In this study, DNA methylation of FHIT, serum folate level and HPV16 status were measured using methylation-specific polymerase chain reaction (MSP), radioimmunoassay (RIA) and polymerase chain reaction (PCR), respectively, in 310 women with a diagnosis of normal cervix (NC, n=109), cervical intraepithelial neoplasia (CIN, n=101) and squamous cell carcinoma of the cervix (SCC, n=101). There were significant differences in HPV16 status (${\chi}^2=36.64$, P<0.001), CpG island methylation of FHIT (${\chi}^2=71.31$, P<0.001) and serum folate level (F=4.57, P=0.011) across the cervical histologic groups. Interaction analysis showed that the ORs only with FHIT methylation (OR=11.47) or only with HPV 16 positive (OR=4.63) or with serum folate level lower than 3.19ng/ml (OR=1.68) in SCC group were all higher than the control status of HPV 16 negative and FHIT unmethylation and serum folate level more than 3.19ng/ml (OR=1). The ORs only with HPV 16 positive (OR=2.58) or with serum folate level lower than 3.19ng/ml (OR=1.28) in CIN group were all higher than the control status, but the OR only with FHIT methylation (OR=0.53) in CIN group was lower than the control status. HPV 16 positivity was associated with a 7.60-fold increased risk of SCC with folate deficiency and with a 1.84-fold increased risk of CIN. The patients with FHIT methylation and folate deficiency or with FHIT methylation and HPV 16 positive were SCC or CIN, and the patients with HPV 16 positive and FHIT methylation and folate deficiency were all SCC. In conclusion, HPV 16 infection, FHIT methylation and folate deficiency might promote cervical cancer progression. This suggests that FHIT may be an effective target for prevention and treatment of cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4297-4302
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• 2015

Background: To evaluate HPV testing by Hybrid Capture II (HCII) in conjunction with cytology in detecting the residual/recurrence disease after treatment of high-grade cervical intraepithelial neoplasia (CIN II-III) with loop electrosurgical excision procedure (LEEP). Materials and Methods: A retrospective review of 158 patients with histologically confirmed CIN II-III who underwent LEEP between January 2011 and October 2012 was conducted. Post-treatment control was scheduled at the 3rd, 6th, 12th and 18th month. All patients were followed up by Pap smear and HR-HPV genotype and viral load testing. Results: Pre-treatment, HR-HPV DNA, was detected in all specimens of the patients. At follow-up, 25 patients were diagnosed as the residual/recurrent disease during the FU visit, among whom, 16 patients with positive margin: 13 patients (52%) with HR-HPV DNA+/cytology+, 2 patients (8%) with HR-HPV DNA+/cytology-, 1 patient (4%) with cytology+/HR-HPV DNA-; 9 patients with clean margin - 5 patients (55.6%) with HR-HPV DNA+/cytology+; 2 patients (22.2%) with HRHPV DNA+/cytology-, 2 patients (22.2%) with cytology+/HR-HPV DNA-. None of them persisting HR-HPV DNA-/cytology-with positive or negative margin was identified as the residual/recurrent disease. The majority of residual/recurrent disease was detected at the 12th and 18th month FU, and there was almost no difference in the sensitivity and negative predictive value (NPV) between at the 3rd month and the 6th month FU visits. 14 residual/recurrence disease (14/46:30.4%) had pre-treatment high viral load (>5 000 RUL/PC) and 11 (11/112, 9.8%) with pre-treatment low viral load, P<0.05. Conclusions: (1) The persistence HR-HPV DNA is the root cause of the residual/recurrent disease for the women treated for high-grade CIN; the pre-treatment viral load and margin can be seen as the predictor. (2) The FU visit beginning at the 6th month post-treatment and lasting at least 24 months with the combination of cytology and HPV testing. (3) Patients with high pre-treatment HPV load, which is considered as one risk of developing the residual/recurrent disease, should be paid more attention (especially above 500RUL/PC) to by clinicians.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3911-3914
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• 2014

Background: To determine the potential clinical utility of tumor markers CEA, TPA, and SCC-Ag for early detection of cervical precancerous lesions. Materials and Methods: A case-control study was carried out on 120 women (46 patients with histologically confirmed cervical precancerous lesions and 74 healthy controls). The significance of serum selected tumor markers in early detection of cervical intraepithelial neoplasia (CIN) were assessed. Results: Of the case group, the rates of CIN I, II, III, was 69.6%, 23.9%, and 6.5%, respectively. According to the manufacturer's cut-off values of 2ng/ml, 5ng/ml, and 70 U/ml for SCC-Ag, CEA and TPA tests, in that order, SCC-Ag test had a sensitivity of 13%, but CEA and TPA tests could not distinguish between case and control groups. The diagnostic sensitivities were highest at cut-off values of 0.55 ng/ml for SCC-Ag, 2.6ng/ml for CEA, and 25.5 U/ml for TPA which were 93%, 61%, and 50%, respectively. However, the area under the receiver operating characteristic curve was the largest for SCC-Ag (0.95 vs. 0.61 and 0.60 for CEA and TPA, respectively). Moreover, there was a highly significant direct correlation between SCC-Ag concentration and the degree of cervical precancerous lesions (r=0.847, p<0.001). Conclusions: The new cutoff of 0.5 for SCC-Ag test might be useful as a tumor marker in Iranian patients with CIN and it needs to be more evaluated by studies with larger populationa.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4977-4980
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• 2015

Background: ASC-US cases are managed according to the current American Society for Colposcopy and Cervical Pathology (ASCCP) guideline in which a human papillomavirus (HPV) test and repeat Pap smear are performed in the next 1 year. Colposcopy in cases of positive high risk HPV and persistent ASC-US or more in subsequent Pap smear is recommended. The HPV test is more expensive and still not currently a routine practice in Thailand. Objective: To identify the risk factors of persisted abnormal Pap smear and the colposcopic requirement rate in women with ASC-US. Materials and Methods: During 2008-2013, this study was conducted in Prapokklao Hospital, Chanthaburi, Thailand. Participants were women who attended gynaecology clinic for cervical cancer screening. Women who had cytological reports with ASC-US were recruited. During the study period, 503 cases were enrolled. Colposcopic requirement was defined as those who were detected with an ASC-US or more in subsequent Pap smears up to 1 year follow-up. Results: The colposcopic referral rate was 23.2 (85/365) percent at 12 months. Prevalence of cervical intraepithelial neoplasia (CIN) 2/3 was 3.3 (12/365) percent. Loss follow-up rate of subsequent Pap smear and colposcopic appointment were 27.4 (138/503) and 48.2 (41/85) percent, respectively. There was no invasive cancer. High risk factors for persisted abnormal Pap smears in subsequent test were premenopausal status, HIV infected patients and non-oral contraceptive pills (COC) users. Conclusions: Referral rate for colposcopy in women with ASC-US reports was rather high. Loss to follow-up rate was the major limitation. Immediate colposcopy should be offered for women who had high risk for silent CIN.

• Journal of the Korea Convergence Society
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• v.13 no.1
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• pp.119-129
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• 2022

Cervical cytology has been widely used as a screening tool for cervical cancer. However, Human papillomavirus (HPV) detection and subtype testing are suggested to overcome the high false-negative rate associated with cytology. We aimed to investigate the clinical usefulness and infection rate in the HPV polymerase chain reaction (PCR) test performed in hospitals. HPV PCR data from 217 patients were analyzed. Analysis of variance revealed a significant difference in the infection rate among different age groups (P=0.015). The biopsy results showed that epithelial cell abnormalities and high HPV-positivity rate was observed in 1 (100%) subject aged <29 years, in 4 out of 5 (80%) patients in their 30s, and in 3 out of 4 (75%) patients aged ≥70 years. The prevalence of HPV infection was very high (46.1%). The highest prevalence (87.5%) was observed among patients in their <29, followed by those in their 30s (67.7%) and those in their 40s (31.9%).A high rate of epithelial cell abnormalities (≥ cervical intraepithelial neoplasia type 1, mild dysplasia) was observed in HPV-infected women aged<30 years. Therefore, extensive research and prevention activities are needed in this age group. HPV PCR testing is recommended to complement cervical cytology

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.511-514
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• 2013

Background: A small but significant proportion of cases with atypical squamous cells of undetermined significance (ASCUS) may harbour CIN 2-3, or even invasive carcinoma. Although immediate colposcopy, HPV-DNA testing or expectant management are three recommended options in ASCUS triage, a consensus does not currently exist on which one of these approaches is the most efficient. In this study, we aimed to compare the performance and cost of immediate colposcopy and colposcopy based on the human papillomavirus (HPV) testing for detecting histologically confirmed high-grade cervical intraepithelial neoplasia (CIN) in women with ASCUS. Materials and Methods: Records of 594 women with an index Papanicolaou smear showing ASCUS were retrospectively analyzed. Women in the immediate colposcopy arm were referred directly to colposcopy (immediate colposcopy group, n=255) and those in the HPV triage arm were proceeded to colposcopy if the high-risk HPV (hrHPV) test was positive (HPV triage group, n=339). High grade CIN (CIN2+) detection rate and treatment costs were compared between the groups. Results: The detected rate of CIN2+ was higher in the HPV triage group compared to immediate colposcopy group (8% vs. 1.6%, p=0.011). In the HPV triage group, the total cost, cost per patient, and the cost for detecting one case of high grade CIN were higher than the immediate colposcopy group (p<0.001). Conclusions: In women with ASCUS cytology, HPV DNA testing followed by colposcopy is more costly than immediate colposcopy, but this approach is associated with a higher rate of CIN2+ detection. This findings suggest that HPV DNA testing combined with cervical cytology could reduce the referral rate to colposcopy.