• 대한의생명과학회지
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• 제11권1호
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• pp.51-56
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• 2005

The detection of high-risk human papilloma virus (HPV) allows us to predict the presence and future development of cervical intraepitheliallesion. In this study, we compared Hybrid Capture II and DNA chip methods for detection of HPV in cervical swab samples. And we evaluated the clinical efficacy and diagnostic performance of HPV DNA chip and Hybrid Capture II for detecting HPV in cervical neoplastic lesions. Seventy four patients were classified into three groups according to their histologic diagnosis: Group I (nonspecific chronic cervicitis), Group II (low-grade squamous intraepithelial lesion (SIL); koilocytosis, and mild dysplasia), and Group III (high-grade SIL;, moderate, severe dysplasia and in situ carcinoma). Cytologic diagnosis were based on the Bethesda System. Hybrid Capture II and DNA chip methods were performed to detect HPV. In 41 of the 74 cervical samples $(55.4\%)$, HPV DNAs were detected by Hybrid Capture II. In Group III, HPV-positive cases were detected in 15 $(20.3\%)$ of 74 patients by Hybrid Capture II. 25 patients with ASCUS cytology were histopathologically examined: 9 cases $(36\%)$ were Group II. In 18 patients with low-grade SIL cytology, 13 cases $(72.2\%)$ were Group II and 3 cases $(16.7\%)$ were Group III. 12 cases $(92.3\%)$ were Group ill of 13 patients with high-grade SIL cytology. The sensitivity of each test was $82\%$ in Hybrid Capture II and $53.9\%$ in DNA chip test. And the specificity was $74.3\%,\;85.7\%$ in Hybrid Capture II and DNA chip. In conclusion, Hybrid Capture II test is more sensitive than DNA chip in detecting women with cervical neoplastic lesions. Especially, in diagnosing of ASCUS, Hybrid Capture II test is more sensitive. Therefore, Hybrid Capture II test for cancer-associated HPV DNA is a viable option in the management of women with ASCUS.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3663-3673
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• 2016

Cervical cancer (CaCx) is the second most fatal cancer contributing to 14% of cancers in Indian females, which account for 25.4% and 26.5% of the global burden of CaCx prevalence and mortality, respectively. Persistent infection with high-risk human papilloma virus (HPV- strains 16 and 18) is the most important risk factor for precursors of invasive CaCx. Comprehensive prevention strategies for CaCx should include screening and HPV vaccination. Three screening modalities for CaCx are cytology, visual inspection with acetic acid, and HPV testing. There is no Indian national policy on CaCx prevention, and screening of asymptomatic females against CaCx is practically non-existent. HPV vaccines can make a major breakthrough in the control of CaCx in India which has high disease load and no organized screening program. Despite the Indian Government's effort to introduce HPV vaccination in the National Immunization Program and bring down vaccine cost, challenges to implementing vaccination in India are strong such as: inadequate epidemiological evidence for disease prioritization, duration of vaccine use, parental attitudes, and vaccine acceptance. This paper reviews the current epidemiology of CaCx and HPV in India, and the current status of HPV vaccination in the country. This article stresses the need for more research in the Indian context, to evaluate interventions for CaCx and assess their applicability, success, scalability and sustainability within the constraints of the Indian health care system.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.3997-4003
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• 2014

Background: Infection with certain human papillomavirus (HPV) genotypes is the most important risk factor related with cervical cancer. The objective of the present study was to investigate the prevalence of HPV infection, the distribution of HPV genotypes and HPV E6/E7 oncogene mRNA expression in Turkish women with different cervical cytological findings in Mersin province, Southern Turkey. Materials and Methods: A total of 476 cytological samples belonging to women with normal and abnormal cervical Pap smears were enrolled in the study. For the detection and genotyping assay, a PCR/direct cycle sequencing approach was used. E6/E7 mRNA expression of HPV-16, 18, 31, 33, and 45 was determined by type-specific real-time NASBA assay (NucliSENS EasyQ$^{(R)}$HPV v1.1). Results: Of the 476 samples, 106 (22.3%) were found to be positive for HPV DNA by PCR. The presence of HPV was significantly more common (p<0.001) in HSIL (6/8, 75%) when compared with LSIL (6/14, 42.9%), ASC-US (22/74, 29.7%) and normal cytology (72/380, 18.9%). The most prevalent genotypes were, in descending order of frequency, HPV genotype 66 (22.6%), 16 (20.8%), 6 (14.2%), 31 (11.3%), 53 (5.7%), and 83 (4.7%). HPV E6/E7 oncogene mRNA positivity (12/476, 2.5%) was lower than DNA positivity (38/476, 7.9%). Conclusions: Our data present a wide distribution of HPV genotypes in the analyzed population. HPV genotypes 66, 16, 6, 31, 53 and 83 were the predominant types and most of them were potential carcinogenic types. Because of the differences between HPV E6/E7 mRNA and DNA positivity, further studies are required to test the role of mRNA testing in the triage of women with abnormal cervical cytology or follow up of HPV DNA positive and cytology negative. These epidemiological data will be important to determine the future impact of vaccination on HPV infected women in our region.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3637-3641
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• 2016

To determine the prevalence of human papillomavirus (HPV) among women with atypical squamous cells of undetermined significance (ASC-US) referred to colposcopy and the implications for clinical management in low- and middle-income countries (LMIC), the present study was conducted. We included 200 women living in $Maring{\acute{a}}$/Brazil referred to colposcopy service between August 2012 and March 2013 due to an abnormal cytology from ASC-US until high-grade intraepithelial lesion (HSIL). HPV was detected and genotyped by polymerase chain reaction (PCR). The mean age was $36.8{\pm}10.5$ years, and women with and without ASC-US had similar mean ages ($37.4{\pm}11.5$ and $36.4{\pm}9.96$ years, respectively). The highest prevalence of ASC-US occurred at 20-24 years (40%). HPV-DNA was positive in 164 (82.0%) women.Of the 57 women with ASC-US, 30 (52.6%) were HPV-DNA-positive and 21 (70%) were high-risk HPV-positive (HR-HPV); the latter was similar to women without ASC-US (76.9%) but with other abnormal cytological findings present. Our data demonstrated that performing tests for HR-HPV can be used for management of women with ASC-US to support the decision of which women should be referred for an immediate or later colposcopy. The same conclusions can be applied to other LMICs for which HPV testing for primary screening has not been adopted.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8209-8213
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• 2014

Background: Cervical cancer is a common, preventable and manageable disease in women worldwide. Objectives: This study was conducted to determine the cost of follow-up for suspicious precancerous cervical lesions within a screening program using Pap smear or HPV DNA test through the decision tree. Materials and Methods: Patient follow-up processes were determined using standard guidelines and consultation with specialists to design a decision tree model. Costs of treatment in both public and private sectors were identified according to the national tariffs in 2010 and determined based on decision tree and provided services (visits to specialists, colposcopy, and conization) with two modalities: Pap smear and HPV DNA test. The number of patients and the mean cost of treatment in each sector were calculated. The prevalence of lesions and HPV were obtained from literature to estimate the cost of treatment for each woman in the population. Results: Follow-up costs were determined using seven processes for Pap smear and 11 processes for HPV DNA test. The total cost of using Pap smear and HPV DNA process for each woman in the population was 36.1$ and 174$ respectively. Conclusions: The follow-up process for patients with suspicious cervical lesions needs to be included in the existing screening program. HPV DNA test is currently more expensive than Pap smear, it is suggested that we manage precancerous cervical lesions with this latter test.

• 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.

• Obstetrics & gynecology science
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• 제61권6호
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• pp.662-668
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• 2018

Objective This study was to identify the risk factors for cytological progression in women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). Methods We analyzed data from women infected with the human papillomavirus (HPV) who participated in the Korean HPV cohort study. The cohort recruited women aged 20-60 years with abnormal cervical cytology (ASC-US or LSIL) from April 2010. All women were followed-up at every 6-month intervals with cervical cytology and HPV DNA testing. Results Of the 1,158 women included, 654 (56.5%) and 504 (43.5%) women showed ASC-US and LSIL, respectively. At the time of enrollment, 143 women tested positive for HPV 16 (85 single and 58 multiple infections). Cervical cytology performed in the HPV 16-positive women showed progression in 27%, no change in 23%, and regression in 50% of the women at the six-month follow-up. The progression rate associated with HPV 16 infection was higher than that with infection caused by other HPV types (relative risk [RR], 1.75; 95% confidence interval [CI], 1.08-2.84; P=0.028). The cytological progression rate in women with persistent HPV 16 infection was higher than that in women with incidental or cleared infections (P<0.001). Logistic regression analysis showed a significant relationship between cigarette smoking and cytological progression (RR, 4.15; 95% CI, 1.01-17.00). Conclusion The cytological progression rate in HPV 16-positive women with ASC-US or LSIL is higher than that in women infected with other HPV types. Additionally, cigarette smoking may play a role in cytological progression.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3455-3460
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• 2012

Objectives: To report the prevalence of atypical squamous cells of undetermined significance and atypical squamous cells-cannot exclude high squamous intraepithelial lesions and to determine the possible association of Pap test results with high-risk human papillomavirus and high squamous intraepithelial lesions in women from Duhok, Iraq. Design: A prospective, observational study was conducted between January 2005 and December 2011. Overall, 596 women with a cervicovaginal Pap test showing atypical squamous cells of undetermined significance and 93 atypical squamous cells-cannot exclude high squamous intraepithelial lesion for whom pathologic follow-up was available were studied. Follow-up consisted of repeat cytology, colposcopy and histology. High risk human papillomavirus DNA testing was performed on exfoliated cervical cells from 106 women, using conventional PCR after at least 36 months from the initial Pap smear. Results: Significantly high proportions of both atypical squamous cells of undetermined significance (87.9%) and atypical squamous cells-cannot exclude high squamous intraepithelial lesion (62.4%) demonstrated no significant lesion on subsequent follow up. Low squamous intraepithelial lesions were observed in 1.7% of cases of atypical squamous cells of undetermined significance and in 5.4% of atypical squamous cells-cannot exclude high squamous intraepithelial lesion. High squamous intraepithelial lesion was demonstrated in 0.8% and 16.1% respectively. In the latter there was also one case of invasive carcinoma. High-risk HPV DNA was demonstrated in 40% of atypical squamous cells of undetermined significance and 57.1% of atypical squamous cells-cannot exclude high squamous intraepithelial lesions. Conclusions: Since both atypical squamous cells of undetermined significance and atypical squamous cells-cannot exclude high squamous intraepithelial lesion identify patients who are at an increased risk for the development of high squamous intraepithelial lesions and a considerable percentage harbor high risk-HPV, both should be retained as diagnostic categories and patients warrant a diligent follow up and testing for high risk-HPV DNA. Colposcopic evaluation and biopsy, when indicated, are a must.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6857-6862
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• 2015

Background: To identify the optimal cost effective strategy for the management of women having ASC-US who attended at King Chulalongkorn Memorial Hospital (KMCH). Design: An Economical Analysis based on a retrospective study. Subject: The women who were referred to the gynecological department due to screening result of ASC-US at King Chulalongkorn Memorial Hospital, a general and tertiary referral center in Bangkok Thailand, from Jan 2008 - Dec 2012. Materials and Methods: A decision tree-based was constructed to evaluate the cost effectiveness of three follow up strategies in the management of ASC-US results: repeat cytology, triage with HPV testing and immediate colposcopy. Each ASC-US woman made the decision of each strategy after receiving all details about this algorithm, advantages and disadvantages of each strategy from a doctor. The model compared the incremental costs per case of high-grade cervical intraepithelial neoplasia (CIN2+) detected as measured by incremental cost-effectiveness ratio (ICER). Results: From the provider's perspective, immediate colposcopy is the least costly strategy and also the most effective option among the three follow up strategies. Compared with HPV triage, repeat cytology triage is less costly than HPV triage, whereas the latter provides a more effective option at an incremental cost-effectiveness ratio (ICER) of 56,048 Baht per additional case of CIN 2+ detected. From the patient's perspective, the least costly and least effective is repeat cytology triage. Repeat colposcopy has an incremental cost-effectiveness (ICER) of 2,500 Baht per additional case of CIN2+ detected when compared to colposcopy. From the sensitivity analysis, immediate colposcopy triage is no longer cost effective when the cost exceeds 2,250 Baht or the cost of cytology is less than 50 Baht (1USD = 31.58 THB). Conclusions: In women with ASC-US cytology, colposcopy is more cost-effective than repeat cytology or triage with HPV testing for both provider and patient perspectives.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10961-10966
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• 2015

Background: Minor cervical cytologic abnormalities include atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Approximately 10-20% of women with minor cytologic abnormalities have histologic high-grade squamous intraepithelial or worse lesions (HSIL+). In Thailand, women with minor cytologic abnormalities have a relatively high risk of cervical cancer, and referral for colposcopy has been suggested. A triage test is useful in the selection of women at risk for histologic HSIL+ to reduce the colposcopy burden. The aim of this study was to assess the performance of high-risk HPV DNA test in triage of women with minor cytologic abnormalities in northern Thailand. Materials and Methods: All women with ASC-US/LSIL cytology who were referred to our colposcopy clinic from October 2010 to February 2014 were included. HPV DNA testing was performed using Hybrid Capture 2 (HC2). All patients received colposcopic examination. Accuracy values of HC2 in predicting the presence of histologic HSIL+ were calculated. Results: There were 238 women in this study (121 ASC-US and 117 LSIL). The HC2 positivity rate was significantly higher in the LSIL group than in ASC-US group (74.8% versus 41.0%, p<0.001). Histologic HSIL+ was detected in 9 women (7.4%) in the ASC-US group and 16 women (13.7%) in the LSIL group (p=0.141). There was no histologic HSIL+ detected among HC2-negative cases (sensitivity and negative predictive value of 100%). The performance of HC2 triage was highest among women aged >50 years with ASC-US cytology. An increase in the cut-off threshold for positive HC2 resulted in a substantial decrease of sensitivity and negative predictive value. Conclusions: HPV DNA testing with HC2 shows very high sensitivity and negative predictive value in triage of women with minor cervical cytologic abnormalities in northern Thailand. An increase of the cut-off threshold for HC2 triage is not recommended in this region.