• The Korean Journal of Cytopathology
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• v.13 no.1
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• pp.14-20
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• 2002

Cytologic and histopathologic features and human papillomavirus (HPV) DNA detection associated with 101 cervicovaginal smears which are ciassified as 'atypical squamous cells of undetermined significance, rule out high grade squamous intraepithelial lesion(ASCUS, R/O HSIL)' were reviewed and compared to 89 smears of 'ASCUS, not otherwise specified(NOS)'. Cytologic fieatures of ASCUS, R/O HSIL included atypical single small cells(36.6%), hyperchromatic tissue flagments(35.6%), atypical metaplastic cells(18.8%), endometrial cell-like clusters(5.9%), and atypical parakeratotic cells(3.0%). A final diagnosis of HSIL on biopsy was assigned to 47(54.0%) of 87 women with ASCUS, R/O HSIL and to 13(14.6%) of 89 women with ASCUS, NOS (p=0.000). There was no difference in HPV DNA detection late between ASCUS, R/O HSIL and ASCUS, NOS smears. These data suggest that subclassification of ASCUS is helpful to manage patients because ASCUS, R/O HSIL is more often associated with an underlying HSIL on biopsy. Therefore, women with ASCUS, rule out HSIL should be actively managed with colposcopic examination.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.469-472
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• 2012

The present study was conducted to assess utility of $p16^{INK4a}$ immunopositivity as a surrogate marker for genomic integration of high-risk human papillomavirus infection (hrHPV). A total of 29 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSILs), 27 high-grade squamous intraepithelial lesions (HSILs) and 53 invasive squamous cell carcinomas (SCCs), histologically-diagnosed between 1st January 2006 to 31st December 2008 at the University of Malaya Medical Centre were stained for $p^{16INK4a}$ (CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany). Immunopositvity was defined as diffuse staining of the squamous cell cytoplasm and or nucleus (involving > 75% of the intraepithelial lesions or SCCs). Staining of basal and parabasal layers of intraepithelial lesions was pre-requisite. One (3.4%) LSIL, 24 (88.9%) HSIL and 46 (86.8%) SCC were $p^{16INK4a}$ immunopositive. All normal squamous epithelium did not express $p16^{INK4a}$. $p16^{INK4a}$ expression was significantly lower (p<0.05) in LSIL compared with HSIL and SCC with no difference in expression between HSIL and SCC. The increased $p16^{INK4a}$ immunopositivity in HSIL and SCC appears in line with the integrated existence of the hrHPV and may provide more insightful information on risk of malignant transformation of cervical squamous intraepithelial lesions than mere hrHPV detection.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7971-7975
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• 2014

Background: From our previous study, we established that cyclin A1 (CCNA1) promoter methylation is strongly correlated with multistep progression of HPV-associated cervical cancer, suggesting potential use as a diagnostic maker of disease. Objectives: The purpose of the present study was to assess the prevalence of CCNA1 promoter methylation in residual cervical cells isolated from liquid-based cytology that underwent hrHPV DNA screening for cervical cancer, and then to evaluate this marker for diagnostic accuracy using parameters like sensitivity, specificity, predictive values and likelihood ratio. Methods: In this retrospective study, histopathology was used as the gold standard method with specimens separated into the following groups: negative (n=31), low-grade squamous intraepithelial lesions (LSIL, n=34) and high-grade squamous intraepithelial lesions or worse (HSIL+, n=32). The hrHPV was detected by Hybrid Capture 2 (HC2) and CCNA1 promoter methylation was examined by CCNA1 duplex methylation specific PCR. Results: The results showed the frequencies of CCNA1 promoter methylation were 0%, 5.88% and 83.33%, while the percentages of hrHPV were 66.67%, 82.35% and 100% in the negative, LSIL and HSIL+ groups, respectively. Although hrHPV infection showed high frequency in all three groups, it could not differentiate between the different groups and grades of precancerous lesions. In contrast, CCNA1 promoter methylation clearly distinguished between negative/LSIL and HSIL+, with high levels of all statistic parameters. Conclusion: CCNA1 promoter methylation is a potential marker for distinguishing between histologic negative/LSIL and HSIL+using cervical cytology samples.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3167-3172
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• 2015

Background: Understanding the history of human papilloma virus (HPV) infection is important for interpretation of a positive HPV DNA screening test, future work-up and treatment. We investigated the transition of HPV DNA test results in Korean women, and analyzed the association of cytology result with transition type. Materials and Methods: We retrospectively reviewed annual HPV DNA test results for 5,274 subjects between January 2005 and December 2012. Each subject had a minimum of five annual tests over the eight-year period. Based on the pattern of results, the transition type for each subject was assigned to one of the following: negative, persistent, latent, transient, and unclassifiable. Associations of cytology results with the HPV DNA transition types, number of positive results, and the durations of positive results were also analyzed. Results: The proportion of abnormal cytology findings decreased in the following order of transition patterns: persistent, latent, transient, and negative. Among transient patterns, a duration of three years or more significantly correlated with cytology results of non-high grade squamous intraepithelial lesion (HSIL; p<0.001). In the persistent group, duration of five years or more correlated with both non-HSIL and HSIL (p<0.001). Latent group showed no correlation with duration. Irrespective of patterns, having five or more positive results was significantly associated with HSIL (p<0.001). Conclusions: Our findings may contribute to better understanding of HPV infection, interpretation of HPV DNA screening results, and prediction of prognosis according to transition type.

• The Korean Journal of Cytopathology
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• v.13 no.1
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• pp.21-27
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• 2002

Papillary immature metaplasia (PIM) of the uterine cervix (Immature condyloma) is a subset of low grade squamous intraepithelial lesion (LSIL) which is frequently associated with human papilloma virus (HPV) types 6 and 11. The histologic features of PIM include filiform papillae lined by evenly spaced immature metaplastic-type cells with frequent nucleoli, mild anisokaryosis, and a low mitotic index. To characterize the cytologic changes associated with PIM, we analyzed 14 cases of PIM from our file. We reviewed biopsy slides and the cervicovaginal smears taken proximate to the time of blopsy. Histologically, nine cases had either flat condyloma (7 cases) or high grade squamous intraepithelial lesion (HSIL) (2 cases). Cytologic changes included cells in various stages of maturation with karyomegaly (14 cases), cells with irregularities in the nuclear membrane (13 cases), intermediate cells with karyomegaly(13 cases), cells with binucleatlon (13 cases), and aborted koliocytes (11 cases) Cervicovaginal smears from all cases were interpreted as atypical squamous cells of undetermined significance (ASCUS), NOS or ASCUS, rule out squamous intraepithelial lesion (SIL) or LSIL in two cases with flat condyloma or HSIL in a case with severe dysplasia. PIM is a distinct histologic entity that can present with a spectrum of cytologic findings, but cytologic findings may resemble variable reactive conditions and immature HSIL. Therefore, it is difficult to diagnose PIM by cytology alone. However, the meticulous efforts for making the cytologic diagnoses which can Induce active management of patients are recommended because PIM is a variant of LSIL and frequently has a flat condyloma or HSIL.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3483-3486
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• 2014

Background: To evaluate the overtreatment rate with the see and treat approach in the management of women with abnormal cervical cytology. Materials and Methods: A retrospective review of patients with abnormal cervical cytology who underwent S&T at MSMC between January 2008 and December 2012 was conducted. Loop electrosurgical excision procedure (LEEP), histological results, cytology and colposcopic impression were analyzed to evaluate overtreatment rate, cyto-histologic correlation and related factors. Results: Average age of S&T cases was 42 years. Ninety seven percents were referred from affiliated health care providers. The study revealed 83.2% patients had HSIL or higher from cervical cytology. Correlation between HSIL and final histology was relatively low at 75% compared to other studies. Overtreatment rate was 28%. Conclusions: S&T was done in 197 patients in a tertiary care health facility with patient satisfaction. Overtreatment occurred, but the rate can be reduced with appropriate recommendations. HSIL Pap smears should be reexamined before S&T while low grade and lesser colposcopic impression groups should obtain conventional colposcopic approach for patient future reproductive benefit.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6093-6097
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• 2015

Background: HPV DNA testing has been recently introduced as an adjunct test to cytology in the follow-up of patients after treatment for cervical lesions using the loop electrosurgical excision procedure (LEEP). The aim of this study was to evaluate the role of HPV testing in the detection of persistent or recurrent disease after LEEP in patients with cervical epithelial lesions in northern Thailand. Materials and Methods: Patients who underwent LEEP as a treatment for histological low-grade (LSIL) or high-grade squamous intraepithelial lesion (HSIL) or worse at Chiang Mai University Hospital between June 2010 and May 2012 were included. Follow-ups were scheduled at 6-month intervals and continued for 2 years using co-testing (liquid-based cytology and Hybrid Capture 2 [HC2]) at 6 months and 24 months and liquid-based cytology alone at 12 and 18 months. Results: Of 98 patients included, the histological diagnoses for LEEP included LSIL in 16 patients, and HSIL or worse in 82 patients. The LEEP margin status was negative in 84 patients (85.7%). At follow-up, 10 patients (10.2%) had persistent/recurrent lesions; 4 among LSIL patients (25.0%) and 6 in the group with HSIL or worse (7.3%). Only 2 of 82 patients (2.4%) with HSIL or worse diagnoses had histological HSIL in the persistent/recurrent lesions. Using histologically confirmed LSIL as the threshold for the detection of persistent/recurrent disease, cytology had a higher sensitivity than HC2 (90.0% versus 70.0%). At the 6-month follow-up appointment, combined cytology and HC2 (co-testing) had a higher sensitivity in predicting persistent/recurrent disease (80.0%) compared with that of cytology alone (70.0%) and HC2 (50.0%). Conclusions: After LEEP with a negative surgical margin, the rate of persistent/recurrent lesions is low. The addition of HPV testing at the 6-month visit to the usual cytology schedule may be an effective approach in the follow-up after LEEP.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4945-4950
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• 2014

Infection with human papillomavirus (HPV) could affect genesis of both cervical and esophageal cancers. The type-specific distribution of HPV in cervical cytology abnormalities of women has remained unclear in Shantou, an esophageal cancer high-incidence area of China. Data from 22,617 women who were subjected to cervical HPV DNA testing with simultaneous cervical cytological examination during 2009-2013 were therefore here retrospectively evaluated in a hospital-based study. Overall, 16.2% (3,584/22,114)of women with normal cytology were HR-HPV positive, with HPV-52 (4.07%) as the most common type followed by -16 (3.63%), and -58 (2.46%). Prevalence of HR-HPV was 50.3% (253/503) in women with cervical cytological abnormalities, of which in ASC-H 71.4%, ASC-US 39.1%, HSIL 80.3% and LSIL 73.7%. HPV-58 (14.12%) was the most common type for all cervical cytological abnormalities, followed by HPV-16 (13.72%), and -52 (12.72%), while the more common HPV-16 type in ASC-H (42.9%) and HSIL (36.1%), HPV-52 and -58 were the most common types for ASC-US (10.3%) and LSIL (25%), respectively. Multiple HPV co-infections were identified in 33.2% (84/253) cytology abnormalities with positive HR-HPV, and the highest prevalence of HPV-58/16 combination in HSIL (28.6%, 6/21) was observed. Our data indicated a relative high prevalence of HPV-58 and -52 in women with cervical cytological abnormalities, which should be considered in the development of next-generation vaccines for Shantou.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6203-6206
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• 2012

The aim of this study was to evaluate the outcomes of women with high-grade squamous intraepithelial lesion (HSIL) smears who had undergone the "see and treat" approach compared to those who underwent a conventional approach. The records of women with HSIL smears undergoing colposcopy at Srinagarind Hospital were reviewed. In those undergoing the conventional approach, the final histological diagnosis was made on the most severe histological results obtained after initial colposcopy. In the "see and treat" group, the final histological diagnosis was made on the examination of LEEP specimens obtained after initial colposcopy. Overtreatment in the see and treat group was defined as the LEEP specimens containing cervical intraepithelial neoplasia (CIN) 1 or less. During the study period, 302 women with HSIL underwent colposcopy. Twenty (6.6%) were nulliparous. One hundred and ninety-four (64.2%) underwent conventional management while the remaining 108 (35.8%) received the see and treat management. The prevalence of underlying high-grade lesions in women undergoing the conventional approach was significantly higher than that observed among women undergoing the see and treat approach (89.2% and 47.2%, respectively, P<0.001). The overtreatment rate in the see and treat group was 52.8%. Multivariate analysis revealed that only parity status was a statistically significant factor for predicting the overtreatment after undergoing the see and treat approach. In conclusion, the overtreatment rate among women undergoing see and treat in this study is notably high and therefore this approach should not be routinely practiced.