• 대한세포병리학회지
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• 제19권2호
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• pp.107-110
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• 2008

We evaluated the usefulness of cervicovaginal cytology as a primary screening test by analyzing the cytologic and histological diagnoses of 2,254 women. Cervicovaginal cytology had 93.0% sensitivity, 86.1% specificity, 88.2% positive predictive value, and 91.7% of negative predictive value. Cervicovaginal cytology as a primary screening test showed much higher specificity but slightly lower sensitivity than HPV DNA testing. However, the sensitivity of cervicovaginal cytology will be improved continuously due to the development of liquid-based cytology. We regard cervicovaginal cytology as a good primary screening test for cervical intraepithelial neoplasia or carcinoma.

• 대한세포병리학회지
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• 제19권2호
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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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• 제15권21호
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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.

• Journal of Microbiology and Biotechnology
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• 제18권4호
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• pp.788-794
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• 2008

The aim of the present study is to estimate the overall prevalence and type distribution of human papillomavirus (HPV) in Korean women, through literature review and meta-analysis. We searched published data for the period between 1995 and 2007 using the following inclusion criteria; (1) studies using type-specific HPV tests, (2) data from Korean female, (3) with cytologic or pathologic results, (4) having more than 20 cases for each subgroup classified by cytologic results, and (5) HPV detection including types 16, 18, and at least one other type. In total, 18 studies (13,842 cases) published up to April 2007 were identified and selected. Adjusted overall HPV prevalence was 23.9% (95% CI: 23.8-24.1%) in women with normal cytology and 95.8% (95% CI: 95.4-96.2%) in women with cervical cancer. Type 16 was predominant regardless of cervical disease status, and type 58 occupied a significantly larger proportion in high-grade cervical intraepitheliallesions and cervical cancer in Korean women. HPV types 58, 33, and 52 together accounted for about 20% of infections in cervical cancer and high-grade intraepitheliallesions. After introduction of HPV prophylactic vaccines, extended protection, especially against types 58, 33, and 52, will be an important issue for cervical cancer prevention in Korea. The future dominant genotypes will require follow-up epidemiological studies with a large-scale, multicentered, and prospective design.

• Asian Pacific Journal of Cancer Prevention
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• 제17권9호
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• pp.4409-4413
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• 2016

Background: Cervical cancer is the second most common of malignancy found in Thai women. Human papillomavirus (HPV) infection is a major cause. The objective of the present study was to evaluate the prevalence of HPV infection and association with abnormal cervical cytology in Thai women. Materials and Methods: This study was conducted at the Gynecologic Clinic, Thammasat University, Pathum Thani, Thailand. A total of 2,144 cases who underwent annual cervical cancer screening by co-testing (liquid based cytology and HPV testing, DNA versus mRNA) during the priod from July 2013 to June 2016 were recruited in this study. Results: Prevalence of positive high risk (HR) HPV DNA and mRNA test were 19.7 and 8.4%, respectively with a statistically significant difference. Majority of cases of abnormal cytology in this study were atypical squamous cells of undetermined significance (ASC-US). In patients with ASC-US, positive HR HPV DNA was greater than in the mRNA group (10.1 and 4.5%, p<0.001). Nonetheless, there was no significant difference in participants with cervical intraepithelial neoplasia (CIN). HPV mRNA test had slightly lower sensitivity but higher negative predictive value (NPV) than the DNA test to detect abnormal cytology during cervical cancer screening (p<0.001). Both HPV test (DNA and mRNA) had equally efficacy to detect high grade precancerous lesion or higher (CIN 2+). Conclusions: Prevalence of HR HPV DNA and mRNA were 19.7 and 8.4 percent, respectively. NPV of HPV mRNA was higher than DNA test. Both tests had equal efficacy to detect CIN 2+ with sensitivity and specificity of 63% vs 55.7% and 83% vs 92%, respectively.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5889-5897
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• 2015

Background: The performance of combined testing visual inspection with acetic acid (VIA) and cervical cytology tests might differ from one setting to another. The average estimate of the testing accuracy across studies is informative, but no meta-analysis has been carried out to assess this combined method. Objective: The objective of this study was to estimate the average sensitivity and specificity of the combined VIA and cervical cytology tests for the detection of cervical precancerous lesions. Materials and Methods: We conducted a systematic review and a meta-analysis, according to the Cochrane Handbook for Systematic Review of Diagnostic Test Accuracy. We considered two cases. In the either-positive result case, a positive result implies positivity in at least one of the tests. A negative result implies negativity in both tests. In the both-positive case, a positive result implies having both tests positive. Eligible studies were identified using Pubmed, Embase, Website of Science, CINHAL and COCRANE databases. True positive, false positive, false negative and true negative values were extracted. Estimates of sensitivity and specificity, positive and negative likelihood (LR) and diagnostic odds ratios (DOR) were pooled using a hierarchical random effect model. Hierarchical summary receiver operating characteristics (HSROC) were generated and heterogeneity was verified through covariates potentially influencing the diagnostic odds ratio. Findings: Nine studies fulfilled inclusion criteria and were included in the analysis. Pooled estimates of the sensitivities of the combined tests in either-positive and both-positive cases were 0.87 (95% CI: 0.83-0.90) and 0.38 (95% CI: 0.29-0.48), respectively. Corresponding specificities were 0.79 (95% CI: 0.63-0.89) and 0.98 (95% CI: 0.96-0.99) respectively. The DORs of the combined tests in either-positive or both-positive result cases were 27.7 (95% CI: 12.5-61.5) and 52 (95% CI: 22.1-122.2), respectively. When including only articles without partial verification bias and also a high-grade cervical intraepithelial neoplasia as a threshold of the disease, DOR of combined test in both-positive result cases remained the highest. However, DORs decreased to 12.1 (95% CI: 6.05-24.1) and 13.8 (95% CI: 7.92-23.9) in studies without partial verification bias for the combined tests in the either-positive and both-positive result cases, respectively. The screener, the place of study and the size of the population significantly influenced the DOR of combined tests in the both-positive result case in restriction analyses that considered only articles with CIN2+ as disease threshold. Conclusions: The combined test in the either-positive result case has a high sensitivity, but a low specificity. These results suggest that the combined test should be considered in developing countries as a primary screening test if facilities exist to confirm, through colposcopy and biopsy, a positive result.

• 대한세포병리학회지
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• 제16권1호
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• pp.18-24
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• 2005

The objective of this study was to ascertain whether or not the high-risk human papillomavirus (HPV) test, when coupled with Papanicolaou (Pap) smears, would prove useful in the screening and management of patients in whom abnormal Pap smear results had been obtained. Concomitant high-risk HPV detection using the hybrid capture II test and colposcopy with a Pap smear were performed with 176 patients, all of whom had been screened for both cervical carcinoma and precancerous lesions. We concomitantly performed colposcopies on these patients. Upon the follow-ups, the histologic diagnoses of these patients were confirmed via either biopsy or hysterectomy. The rate of high-risk HPV detection was correlated with cytologic diagnoses and colposcopic findings. The group composed of the high-risk HPV-positive ASCUS patients exhibited a 55.7% rate of cervical intraepithelial neoplasia (CIN), a significantly higher rate than the 7.5% result obtained in the high-risk HPV-negative ASCUS group. HPV test showed high sensitivity (87%) and low specificity (62.6%) in detection of CIN and colposcopy also showed high sensitivity (88%) and low specificity (22%). Any combination of these tests improve sensitivity, but not specificity. High-risk HPV tests, when coupled with Pap smears, constituted a useful triage approach with regard to colposcopy-directed biopsies in patients in whom a cytologic diagnosis of ASCUS had been rendered.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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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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• 제15권17호
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• pp.7085-7090
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• 2014

Objective: To make the clinical evaluation of a solid-state human papillomavirus (HPV) sampling medium in combination with an economical HPV testing method ($careHPV^{TM}$) for cervical cancer screening. Methods: 396 women aged 25-65 years were enrolled for cervical cancer screening, and four samples were collected. Two samples were collected by woman themselves, among which one was stored in DCM preservative solution (called "liquid sample") and the other was applied on the Whatman Indicating FTA $Elute^{(R)}$ card (FTA card). Another two samples were collected by physician and stored in DCM preservative solution and FTA card, respectively. All the samples were detected by $careHPV^{TM}$ test. All the women were administered a colposcopy examination, and biopsies were taken for pathological confirmation if necessary. Results: FTA card demonstrated a comparable sensitivity of detecting high grade Cervical Intraepithelial Neoplasia (CIN) with the liquid sample carrier for self and physician-sampling, but showed a higher specificity than that of liquid sample carrier for self-sampling (FTA vs Liquid: 79.0% vs 71.6%, p=0.02). Generally, the FTA card had a comparable accuracy with that of Liquid-based medium by different sampling operators, with an area under the curve of 0.807 for physician &FTA, 0.781 for physician &Liquid, 0.728 for self & FTA, and 0.733 for self &Liquid (p>0.05). Conclusions: FTA card is a promising sample carrier for cervical cancer screening. With appropriate education programmes and further optimization of the experimental workflow, FTA card based self-collection in combination with centralized $careHPV^{TM}$ testing can help expand the coverage of cervical cancer screening in low-resource areas.