• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3201-3206
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• 2016

Purpose: To evaluate the expression of p16 and Ki67 in cervical intraepithelial neoplasia (CIN) and cancer. Materials and Methods: We performed a immunohistochemical study of p16 and Ki67 in 243 cervical tissues - 53 non-dysplastic lesions, 106 CIN1, 61 CIN2/3 and 23 squamous cell carcinomas. The expression of p16 and Ki67 was interpreted independently by 2 researchers and the sensitivity and specificity to detect clinically significant lesions (${\geq}CIN2$) were determined. Results: The overall agreement results of positive or negative immunostaining of intra-inter observer variability were 0.659 for p16 and 0.808 for Ki67. p16 expression was demonstrated in 91.3% of invasive carcinomas, 78.7% of CIN2/3, 10.4% of CIN1 and 9.4% of non-dysplasic lesions. The corresponding Ki67 expression was: 100% of all invasive carcinomas, 75.4% of CIN2/3, 22.6% of CIN1, and 11.3% with non-dysplasia. The expression was significantly different between CIN2/3 vs CIN1 for both p16 and Ki67 (p-values <0.001 both), and cancer vs CIN2/3 for Ki67 (p-value 0.008). The differences were not significant between CIN1 vs non-dysplasia (p-values 1.000 for p16 and 0.130 of Ki67), and cancer vs CIN2/3 for p16 (p value 0.219). The sensitivity and specificity to detect > CIN2 were 84.5% and 90.5% by p16 and 82.1% and 88.6% by Ki67. Conclusions: The rates for 16 and Ki67 expression were directly associated with the severity of cervical lesions. Significant differences in these markers expression may be useful in cases with equivocal histologic features among cervical intraepithelial lesions, but not between CIN1 and non-dysplastic lesions. The two markers had high sensitivity and specificity in determining >CIN2.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2327-2331
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• 2015

Purpose: To determine the accuracy of visual inspection with acetic acid (VIA) in detecting high-grade cervical intraepithelial neoplasia (CIN) in pre- and post-menopausal women with atypical squamous cells of undetermined significance (ASC-US) and low grade squamous intraepithelial lesion (LSIL) Papanicolaou (Pap) smears. Materials and Methods: Two hundred women (150 pre-menopausal and 50 post-menopausal) with ASC-US and LSIL cytology who attended the colposcopy clinic, Thammasat University Hospital, between March 2013 and August 2014 were included. All women underwent VIA testing and colposcopy by gynecologic oncologists. Diagnostic values of VIA testing including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting high-grade CIN were determined using the histopathology obtained from colposcopic-directed biopsy as a gold standard. Results: VIA testing was positive in 54/150 (36%) pre-menopausal women and 5/50 (10%) post-menopausal women. Out of 54 pre-menopausal women with positive VIA testing, 15 (27.8%) had high-grade CIN and 39 (72.2%) had either CIN 1 or insignificant pathology. Ten (10.4%), 43 (44.8%) and 43 (44.8%) out of the remaining 96 pre-menopausal women with negative VIA testing had high-grade CIN, CIN 1 and insignificant pathology, respectively. Out of 5 post-menopausal women with positive VIA testing, there were 4 (80%) women with high-grade CIN, and 1 (20%) women with insignificant pathology. Out of 45 VIA-negative post-menopausal women, 42 (93.3%) women had CIN 1 and insignificant pathology, and 3 (6.7%) had high-grade CIN. Sensitivity, specificity, PPV and NPV of the VIA testing were 59.4%, 76.2%, 32.2% and 90.8%, respectively (60%, 68.8%, 27.8% and 89.6% in pre-menopausal women and 57.1%, 97.7%, 80% and 93.3% in post-menopausal women). Conclusions: VIA testing may be used as a screening tool for detecting high-grade CIN in women with minor cervical cytological abnormalities in a low-resource setting in order to lower the rate of colposcopy referral.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2067-2073
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• 2016

Purpose: The aim of the study was to identify risk and protective factors/markers for cervical cancer and cervical intraepithelial neoplasia 3 (CIN3) in Israeli Jewish women in order to settle the discrepancy of low incidence rate of cervical cancer and relatively high incidence rate of CIN3. Materials and Methods: We conducted two case control studies, which examined the association between potential risk and protective factors/markers for cervical cancer or CIN3 using self administered detailed questionnaires. Results: For studying cervical cancer, 40 cases and 40 matched controls were interviewed. In the univariable and multivariable analyses older age, depression or anxiety and ever smoking seemed to act as independent risk factors/markers, while older age at first intercourse was protective. For studying CIN3, 99 cases and 79 controls were interviewed. Multivariable analysis has demonstrated that being born in Israel, depression or anxiety and ever smoking were independent risk factors/markers for CIN3. Conclusions: The risk factors/markers studied, that were associated with cervical cancer or CIN3 among Jewish women in Israel, are similar to those reported in other parts of the world, and do not explain the observed discrepancy of high in-situ cervical cancer rates and low invasive cervical cancer incidence in Israel.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2411-2414
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• 2016

Purpose: To determine the incidence of high-grade cervical intraepithelial neoplasia (CIN2-3) among patients with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou (Pap) smears. Materials and Methods: One-hundred and eighty-seven patients with ASC-US Pap smears who underwent colposcopy with histological study were enrolled between September 2007 and August 2015. Patient factors (including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners) were obtained. Logistic regression analysis was used to evaluate clinical factors associated with CIN2-3. Results: CIN was diagnosed in 92 of 187 women (49.2%). Sixty-one of these (32.6%) had CIN1 and 31 (16.6%) had CIN2-3. There was no woman who had invasive cancer. There was no correlation of high-grade CIN with factors in this study including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners. Conclusions: Data from this study showed no invasive cervical cancer was found in patients with ASC-US. There was no patient factor associated with high grade intraepithelial neoplasia in patients with ASC-US Pap smears.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1643-1647
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• 2013

Background: To identify the risk factors and assess the role of survivin in predicting progessivity precancerous cervical lesions. Materials and Methods: This case-control study was conducted from October 2009 until May 2010. We obtained 74 samples, classified according to the degree of cervical intraepithelial neoplasia (CIN): 19 samples for CIN 1, 18 samples for CIN 2, 18 samples for CIN 3, and 19 samples as controls. Demographic profiles and risk factors assesment, histopathologic examination, HPV DNA tests, immunocytochemistry (ICC) and immunohistochemistry (IHC) staining for survivin expression were performed on all samples. Data was analyzed with bivariate and multivariate analysis. Results: Multivariate analysis revealed significant risk factors for developing precancerous cervical lesions are age <41 years, women with ${\geq}2$ sexual partners, course of education ${\geq}13$ years, use of oral contraceptives, positive high-risk HPV DNA, and high survivin expression by ICC or IHC staining. These factors were fit to a prediction model and we obtained a scoring system to predict the progressivity of CIN lesions. Conclusions: Determination of survivin expression by immunocytochemistry staining, along with other significant risk factors, can be used in a scoring system to predict the progressivity of CIN lesions. Application of this scoring system may be beneficial in determining the action of therapy towards the patient.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.305-308
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• 2012

Objective: To assess the health and economic burden of human papillomavirus (HPV)-related diseases (cervical cancer, cervical intraepithelial neoplasia (CIN) 1/2/3, and genital warts) in Singapore over a period of 25 years beginning in 2008. Methods: Incidence-based modeling was used to estimate the incidence cases and associated economic burden, with the assumption that age-stratified incidence rates will remain the same throughout the period of 25 years. The incidence rates in 2008 were projected based on data obtained from the National Cancer Registry for cervical cancer, and from a combination of published data and hospital registry review for CIN1/2/3 and genital warts. The population growth rate was factored into the projection of incidence cases over time. Direct cost data per cervical cancer and per CIN1/2/3 case were obtained from the financial database of large local hospitals while cost data for genital warts were obtained from the National Skin Center; these costs were multiplied by the number of incidence cases to produce an aggregate estimate of the economic burden over the 25-year period (in 2008 Singapore dollars) using a 3% discount rate. Results: The total number of incidence cases of HPV-disease over 25 years beginning in 2008 was estimated to be 60,183, including 8,078 for cervical cancer, 11,685 for CIN 2/3, 8,849 for CIN1, and 31,572 for genital warts. The estimated total direct cost was 83.2 million Singapore Dollars over 25 years: 57.6 million attributable to cervical cancer, 13.0 million to CIN2/3, 6.83 million to CIN1, and 5.70 million to genital warts. Conclusion: HPV-related diseases are expected to impose significant health and economic burden on the Singapore healthcare resources in the next 25 years.

• Journal of Yeungnam Medical Science
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• v.32 no.2
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• pp.90-97
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• 2015

Background: Contrast-induced nephropathy (CIN) can cause serious adverse effects. To reduce the occurrence of CIN related computed tomography (CT) in emergency patients, we assessed the respective roles of serum creatinine (SCr) alone and estimated glomerular filtration rate (eGFR) as an early predictor for CIN related CT. Methods: For patients with SCr <1.5 mg/dL who underwent CT in emergency department (ED) between September 2012 and October 2013, we assessed the prevalence of CIN and its adverse effects. The Modification of Diet in Renal Disease Study (MDRD) and Cockcroft-Gault (CG) formula was used for the calculation of eGFR. Practical calculation was performed by electronic medical record (EMR) system for MDRD and internet calculating service for CG. And we investigated the prevalence of CIN in eGFR $<60mL/min/1.73m^2$ before CT. Results: A total of 1,555 patients were enrolled. The prevalence of CIN after CT was 4.6% and it showed correlation with renal deterioration, increased in-hospital mortality, and prolonged hospitalization. Despite baseline SCr <1.5 mg/dL, among enrolled patients, 11.3% as MDRD equation and 29.5% as CG formula were $<60mL/min/1.73m^2$ and in this condition, the prevalence of CIN was significantly high (odds ratio was 2.87 [1.64-5.02] as MDRD equation and 2.03 [1.26-3.29] as CG formula). Conclusion: Just SCr <1.5mg/dL was not appropriate to recognize preexisting renal insufficiency, but eGFR using MDRD equation was useful in predicting the risk of CIN related CT in ED. Using EMR, calculation of eGFR can be easier and more convenient.

• Biomedical Science Letters
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• v.22 no.2
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• pp.37-45
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• 2016

High risk human papillomavirus (HR-HPV) is major risk factor for uterine cervical cancer. There are approximately 15 types of HR-HPV. Liquid based cytology samples (116 samples) with high grade cervical lesions belonging to cervical intraepithelial neoplasia (CIN) 2, CIN 3, carcinoma in situ (CIS) and squamous cell carcinoma (SCC) were used after histologic confirmation. HR-HPV genotype assay was conducted using DNA chips. The HR-HPV infection rate was 81.9% with SCC samples showing the highest HR-HPV infection rate of 31%. CIN 3, CIS and CIN 2 showed infection rates of 25%, 16.4% and 9.5%, respectively. According to age with HR HPV infection rate, the 30~39 years-old group showed the highest infection rate by 92.3%. According to distribution with HR HPV genotyping, HPV 16 showed the highest infection rate by 42.3% whereas HPV 33 and HPV 58 showed infection rates of 11.7% and 10.8%, respectively. HPV 18 which is the second most common infected HPV genotype in the world showed 3.6%. Of the three most common oncogenic HR-HPV genotypes in CIN 2, we detected HPV 16, 35, 58; CIN 3 was HPV 16, 33, 58; CIS was HPV 16, 58, 33 (35/52); and SCC was HPV 16, 33, and 18 (31/52/58). Among the HPV 18, CIN 2, CIN 3, CIS and SCC showed 0.9%, 0.9%, 0% and 1.8%, respectively. The most often used preventive vaccines for cervical cancers use HPV 16 and HPV 18 as targets. However, results derived from this study suggest that a preventive vaccine against HPV 16 and HPV 18 would not be optimal for populations in this study.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.7
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• pp.935-944
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• 2013

Essential oils have been shown to favorably effect in vitro ruminal fermentation, but there are few in vivo studies that have examined animal responses. The objective of this study was to evaluate the effects of thyme (THY) and cinnamon (CIN) essential oils on feed intake, growth performance, ruminal fermentation and blood metabolites in feedlot calves fed high-concentrate diets. Twelve growing Holstein calves ($213{\pm}17kg$ initial BW) were used in a completely randomized design and received their respective dietary treatments for 45 d. Treatments were: 1-control (no additive), 2-THY (5 g/d/calf) and 3-CIN (5 g/d/calf). Calves were fed ad libitum diets consisting of 15% forage and 85% concentrate, and adapted to the finishing diet by gradually increasing the concentrate ratio with feeding a series of transition diets 5 wk before the experiment started. Supplementation of THY or CIN did not affect DMI and ADG, and feed efficiency was similar between treatment groups. There were no effects of additives on ruminal pH and rumen concentrations of ammonia nitrogen and total VFA; whereas molar proportion of acetate and ratio of acetate to propionate decreased, and the molar proportion of propionate increased with THY and CIN supplementation. Rumen molar concentration of butyrate was significantly increased by adding CIN compared to control; but no change was observed with THY compared with control group. No effects of THY, or CIN were observed on valerate, isobutyrate or isovalerate proportions. Plasma concentrations of glucose, cholesterol, triglyceride, urea-N, ${\beta}$-hydroxybutyrate, alanine aminotransferase and aspartate aminotransferase were not changed by feeding THY or CIN. Results from this study suggest that supplementing a feedlot finishing diet with THY or CIN essential oil might be useful as ruminal fermentation modifiers in beef production systems, but has minor impacts on blood metabolites.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.4989-4992
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• 2013

Aim: To compare p16INK4a immunocytochemistry with the HPV polymerase chain reaction in predicting high grade cervical squamous intraepithelial lesions. Materials and Methods: This diagnostic case-control study was conducted from January 2010 until December 2010. We obtained 30 samples, classified according to the degree of cervical intraepithelial neoplasia (CIN): 11 samples for CIN 1, 9 samples for CIN 2, and 10 samples for CIN 3. HPV PCR, p16INK4a immunocytochemistry, and histopathological examination were performed on all samples. Statistical analysis was conducted using SPSS 20.0. Results: In predicting CIN 2-3, we found p16INK4a to have similar specificity and positive predictive value as HPV PCR (95%, 97.2% vs 96.7%), but better sensitivity (87.5% vs 72.5%) and negative predictive value (82.1% vs 67.6%). The most prevalent types of high-risk HPV in our study were HPV 33, 35, 58, 52, and 16. Conclusions: p16INK4a has better diagnostic values than HPV PCR and may be incorporated in the triage of ASCUS and LSIL to replace HPV PCR. Genotype distribution of HPV differs in each region, providing a challenge to develop HPV vaccines based on the epidemiology of HPV in that particular region.