• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5153-5158
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• 2015

Infection with high-risk human papillomavirus (HR-HPV) is an essential cause of cervical cancer. Because of substantial geographical variation in the HPV genotype distribution, data regarding HPV type-specific prevalence for a particular country are mandatory for providing baseline information to estimate effectiveness of currently implemented HPV-based cervical cancer prevention. Accordingly, this review was conducted to evaluate the HR-HPV genotype distribution among Thai women with precancerous cervical lesions i.e. cervical intraepithelial neoplasia grade 2-3 (CIN 2-3), adenocarcinoma in situ (AIS), and invasive cervical cancer by reviewing the available literature. The prevalence of HR-HPV infection among Thai women with CIN 2-3 ranged from 64.8% to 90.1% and the three most common genotypes were HPV 16 (38.5%), HPV 58 (20.0%), and HPV 18 (5.5%). There were high squamous cell carcinoma/CIN 2-3 prevalence ratios in women with CIN 2-3 infected with HPV 33 and HPV 58 (1.40 and 1.38, respectively), emphasizing the importance of these subtypes in the risk of progression to invasive cancer among Thai women. Data regarding the prevalence and genotype distribution of HR-HPV in Thai women with AIS remain unavailable. Interesting findings about the distribution of HPV genotype in cervical cancer among Thai women include: (1) a relatively high prevalence of HPV 52 and HPV 58 in invasive squamous cell carcinoma; (2) the prevalence of HPV 18-related adenocarcinoma is almost double thepreviously reported prevalence, and (3) 75% of neuroendocrine carcinomas are HPV18-positive when taking into account both single and multiple infections.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3461-3464
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• 2014

Background: To determine the frequency of dysplastic lesions in the endocervical curettage (ECC) specimens of women with ASC-US and LSIL Pap and to evaluate the possible factors associated with high grade dysplasia in those ECC specimens. Materials and Methods: Two hundred and sixty patients with ASC-US and LSIL cytologic smears who underwent an ECC at the time of colposcopic examination during January 2010 and December 2012 were reviewed. Demographic and clinicopathologic data were collected. Multivariate analysis using binary logistic regression was used to identify factors that might be associated with high grade endocervical dysplasia. Results: The frequency of endocervical dysplasia was 7.7% (20 out of 260 patients). Cervical intraepithelial neoplasia (CIN) 1 and CIN 2-3 lesions in the endocervical canal were observed in 12 and 8 patients, respectively. No microinvasive or invasive cervical cancers were identified. There was no difference in the frequency of high grade endocervical dysplasia between the patients with satisfactory and unsatisfactory colposcopic examinations (1.4% vs 5.1%, respectively, p=0.087). A multivariate logistic regression analysis demonstrated a significant association between high grade CIN on ectocervical biopsy as well as LSIL cytologic smears and high grade dysplasia in endocervical canal (OR=0.046, 95%CI=0.007-0.288; p=0.001 and OR=0.154, 95%CI=0.025-0.942; p=0.043, respectively). Conclusions: The frequency of high grade endocervical dysplasia in women with ASC-US and LSIL cytologic smears was low. Therefore, routine performance of ECC in those women is debatable. High grade ectocervical dysplasia and LSIL cytologic smears may be used as predictors for high grade dysplasia in endocervical canal and ECC in these patients is reasonable.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1023-1026
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• 2013

Cervical cancer is the most important female gynecological cancer, the second leading cause of cancer mortality in women worldwide and the second most common cancer in Thai women. The major cause of cervical cancer is persistent infection of human papillomavirus (HPV), leading to abnormal epithelial lesions, with progression to precancerous and invasive cancer. This study was conducted to investigate the frequency and type distribution of HPV in Thai women who had abnormal cytology. HPV detection from FFPE confirmed abnormal of high grade cervical intraepithelial lesions were for SPF-10-Innogenic Line Probe Assay. HPV-positivity was detected in 320/355 cases (90.14%) and HPV-negativity in 35/355 (9.86%). HPV-positive was found 147/320 cases (41.4%) of single infection, whereas 173/320 cases (48.7%) showed the multiple HPV infection. The most common seven types were HPV-16, -52, -18, -11, -51, -31 and -33, in that order. HPV 16 and 18, the important oncogenic HPV type, were observed in 64.8% of HSIL cases. Interestingly, a high proportion of multiple infections was found in this study and more than ten types could be detected in one case. Therefore, HPV infection screening program in women is essential, particularly in Thailand. Effective primary and secondary prevention campaigns that reinforce HPV screening for HPV detection and typing may be decrease the incidence and mortality of cervical cancer in the future and may lead to significantly improve the quality of life in Thai women.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.91-96
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• 2012

Objectives: To determine the prevalence of HPV and cervical neoplasia among HIV-infected women in southwestern China. Methods: Cervical cytology, HPV detection by Hybrid Capture-$2^{TM}$ assay, and diagnostic colposcopy were followed by cervical biopsy if indicated. Logistic regression analysis was used to analyze associations between HPV co-infection and cervical intraepithelial neoplasia (CIN), and HIV-related clinical and laboratory parameters. Results: Colposcopic-histopathologically proven CIN2+ lesions were present in 7/83 (8.4%) HIV-infected women. Nearly half (41/83, 43%) were co-infected with carcinogenic HPV genotypes. HPV co-infection was higher in women with colposcopic-histopathologically proven CIN2+ lesions than women with $cells/{\mu}L$ had higher CIN2+ prevalence after adjusting for current ART status and age (adjusted OR: 6.3, 95% CI: 1.1, 36.5). Conclusions: HIV/AIDS care and treatment programs should integrate effective cervical cancer prevention services to mitigate the risk of invasive cervical cancer among HIV-infected women in China.

• The Journal of Korean Obstetrics and Gynecology
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• v.33 no.2
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• pp.44-62
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• 2020

Objectives: The purpose of this study is to evaluate the effectiveness of herbal medicine for recovery and treatment of cervical intraepithelial neoplasia (CIN) after loop electrosurgical excision procedure (LEEP). Methods: We searched two english, one chinese and four korean database up to November 4, 2019. Randomised controlled trials (RCTs) were eligible. Primary outcome included Human papilloma virus (HPV) clearance rate and the effective ratio of treatment. And vaginal bleeding time and volume, improvement of symptoms, and recovery of wound were regarded as secondary outcomes. The risk of bias was assessed by two independent authors using the Cochrane risk of bias tool. Results: Of 47 screened, 10 RCTs were included. Number of participants per study ranged from 58 to 360. The studies which used HPV clearance rate as primary outcome were considered as low risk of bias. Most of the studies had considerable heterogeneity in terms of type of intervention, comparison and time-points for outcome measurement. Compared to LEEP alone, herbal vaginal suppository combined group showed favorable results for HPV clearance in patients (5 studies, n=627, 95% CI 1.26 to 1.55, I²=75%). And compared to LEEP alone, herbal external application also showed favorable results for HPV clearance in patients (2 studies, n=252, 95% CI 1.19 to 1.61, I²=86%). Three studies reported mild and temporary adverse events, and no serious adverse events were reported. Conclusions: The studies showed that herbal medicine can significantly effective on recovery of CIN after LEEP. However, included studies suffered from incomplete reporting, high or unclear risk of bias and substantial heterogeneity between studies. In the Future, further high-quality RCTs are needed to prove effectiveness of herbal medicine for CIN after LEEP and reduce the risk of bias.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2051-2055
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• 2014

Background: To evaluate the performance of Siriraj liquid-based cytology (LBC) for cervical neoplasia screening after increasing use of this technology. Materials and Methods: Cytological reports of 103,057 Siriraj-LBC specimens obtained in 2007-2009 were compared with those of 23,676 specimens obtained in 2006. Results: Comparing with the year 2006, the 2007-2009 patients were slightly older ($43.4{\pm}12.yr$ vs $42.7{\pm}12.2yr$, p <0.001), and their specimens had much lower proportion of unsatisfactory slides (OR=0.06, 95%CI 0.04-0.09) with comparable detection rates (3.96% vs 3.70%, p=0.052) but different proportions of various cytological abnormalities (p<0.001). The 2007-2009 Siriraj-LBC had a negative predictive value (NPV) for cervical intraepithelial neoplasia 2+ (CIN2+) of 97.6% and an overall positive predictive value (PPV) of 43.9%. The PPV for CIN2+ varied with types of abnormal cytology, from 13.7% to 93.8% in atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells cannot exclude HSIL (ASC-H), high-grade squamous intraepithelial lesion (HSIL), atypical glandular cells (AGC), to squamous cell carcinoma (SCC), respectively. The PPVs for CIN2+ in ASCUS and LSIL were comparable, but the PPV for CIN1 was higher for LSIL than for ASCUS (41.63% vs 16.32%). Conclusions: Siriraj-LBC has demonstrated a stable detection rate and NPV for CIN2+ of >95% since the first year of use. The comparable PPVs for CIN2+ of ASCUS and LSIL suggests that these two conditions may undergo similar management; other cytological abnormalities need immediate evaluation.

• 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.15 no.15
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• pp.6145-6150
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• 2014

Toll-like receptors (TLRs) are expressed in immune and tumor cells and recognize pathogen-associated molecular patterns. Cervical cancer (CC) is directly linked to a persistent infection with high risk human papillomaviruses (HR-HPVs) and could be associated with alteration of TLRs expression. TLR9 plays a key role in the recognition of DNA viruses and better understanding of this signaling pathway in CC could lead to the development of novel immunotherapeutic approaches. The present study was undertaken to determine the level of TLR9 expression in cervical neoplasias from Tunisian women with 53 formalin-fixed and paraffin-embedded specimens, including 22 samples of invasive cervical carcinoma (ICC), 18 of cervical intraepithelial neoplasia (CIN), 7 of condyloma and 6 normal cervical tissues as control cases. Quantification of TLR9 expression was based on scoring four degrees of extent and intensity of immunostaining in squamous epithelial cells. TLR9 expression gradually increased from CIN1 (80% weak intensity) to CIN2 (83.3% moderate), CIN3 (57.1% strong) and ICC (100% very strong). It was absent in normal cervical tissue and weak in 71.4% of condyloma. The mean scores of TLR9 expression were compared using the Kruskall-Wallis test and there was a statistical significance between normal tissue and condyloma as well as between condyloma, CINs and ICC. These results suggest that TLR9 may play a role in progression of cervical neoplasia in Tunisian patients and could represent a useful biomarker for malignant transformation of cervical squamous cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7231-7235
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• 2015

This study was conducted to determine whether advancing age is an independent predictor of increased risk of high-grade pathologies among women referred for colposcopy after abnormal cervical cytology. Medical records were reviewed for women with abnormal cervical cytology who underwent colposcopy at Khon Kaen University Hospital. Logistic regression was used to determine the independent impact of age on the risk of high-grade pathologies. Mean age of the women was 42.8 years. Of 482 women, 97 (20.1%) were postmenopausal, and 92 (19.1%) were nulliparous. The rate of high-grade pathologies included cervical intraepithelial neoplasia 2-3, 99 (20.5%), adenocarcinoma in situ, 4 (0.8%), cervical cancer, 30 (6.2%), and endometrial cancer, 1 (0.2%). The prevalence of significant lesions was 26.9% (95% CI, 23.1%-31.2%). In total, 31 women had cancers (6.4%; 95% CI, 4.4%-9.0%). When controlling for smear types and parity, age was noted to be a significant independent predictor of high-grade histopathology. Women older than 35-40 years were approximately 2 times as likely to have severe histopathology as the younger women. This study illustrates the substantial risk of underlying significant lesions especially invasive cancer in Thai women with abnormal cervical cytology. Age was a significant independent factor predicting the risk of high-grade pathologies.