• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3645-3651
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• 2012

Conventional pap smear (CPS) examination has been the mainstay for early detection of cervical cancer. However, its widespread use has not been possible due to the inherent limitations, like presence of obscuring blood and inflammation, reducing its sensitivity considerably. Automated methods in use in developed countries may not be affordable in the developing countries due to paucity of resources. On the other hand, manual liquid based cytology (MLBC) is a technique that is cost effective and improves detection of precursor lesions and specimen adequacy. Therefore the aim of the study was to compare the utility of MLBC with that of CPS in cervical cancer screening. A prospective study of 100 cases through MLBC and CPS was conducted from October 2009 to July 2010, in a Medical College in India, by two independent pathologists and correlated with histopathology (22 cases). Morphological features as seen through MLBC and CPS were compared. Subsequently, all the cases were grouped based on cytological diagnosis according to two methods into 10 groups and a subjective comparison was made. In order to compare the validity of MLBC with CPS in case of major diagnoses, sensitivity and specificity of the two methods were estimated considering histological examination as the gold standard. Increased detection rate with MLBC was 150%. The concordance rate by LBC/histopathology v/s CPS/histopathology was also improved (86% vs 77%) The percentage agreement by the two methods was 68%. MLBC was more sensitive in diagnosis of LSIL and more specific in the diagnosis of inflammation. Thus, MLBC was found to be better than CPS in diagnosis of precursor lesions. It provided better morphology with increased detection of abnormalities and preservation of specimen for cell block and ancillary studies like immunocytochemistry and HPV detection. Therefore, it can be used as alternative strategy for cervical cancer prevention in limited resource settings.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5993-5999
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• 2015

Background: Molecular testing for human papillomavirus (HPV) is the most objective and reproducible of all cervical cancer screening tests and also less demanding in terms of training and quality assurance. However, there is an impending need for cost effective molecular HPV testing methods with sampling ease, easy storage measures and minimum turn around times suitable for a low resource setting. Objective : Our aim was to evaluate the feasibility of using a fast transfer analysis (FTA) mini elute cartridge for cervical sampling to identify high risk HPV by real time PCR and to compare molecular HPV testing and Pap cytology testing to predict histologically confirmed cervical precancer (CIN 2+ lesions) in a cervical cancer prevention program. Materials and Methods: This was conducted as a pilot study (n=200) on women sampled using FTA mini elute cartridges, genotyped by two different real time PCR assays, detecting 13 high risk HPV (HR HPV) species, including HPV16 along with its physical DNA status. Results obtained from each of the tests were compared and analysed using suitable statistical tests. Results: With FTA mini elute cartridge samples HR HPV positivity was seen in 48/200 (24%). Of these, presence of HPV 16 DNA was observed in 28/48 (58.3%) women. High risk HPV was positive in 20% (37/185) of women with benign cytology and 73.3% (11/15) of women with abnormal cytology findings. A very significant correlation (${\chi}^2=22.090$ ; p=0.000) was observed between cytology and HR HPV findings showing an increasing trend of HR HPV prevalence in 50% (1/2) of LSIL, 75% (3/4) of HSIL and 100% (3/3) of SCC. Of the CIN 2+ lesions identified by histopathology, 88.9% (8/9) had HR HPV. A significant association (${\chi}^2=11.223$ ; p=0.001) of HR HPV and histopathologically confirmed CIN 2+ lesions was found. Sensitivity of the two tests were comparable but specificity of Pap testing was better (90.7% vs 70.4%) to predict histopathologically diagnosed cervical precancers. Conclusions: The current study explored the feasibility of using a FTA mini elute cartridge for cervical sampling for the first time in India as a part of a community based cervical cancer prevention program. We suggest that FTA based sampling is suitable and feasible for real time based HPV testing. Molecular HR HPV testing can be more sensitive and useful to identify high risk women requiring Pap testing which is more specific to detect histologically confirmed cervical precancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4223-4228
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• 2015

Objective: To investigate the diagnostic value of the R-way colposcopic evaluation system (R-way system) in cervical cancer screening. Materials and Methods: Between August 2013 and August 2014, a total of 1,059 cases referred to colposcopy in Peking University First Hospital were studied using both the R-way system and conventional colposcopy. Our study evaluated and compared the diagnostic ability of the two methods in detecting high-grade lesions and cervical cancer (hereinafter called CIN2+). Evaluation indicators including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Youden index and the area under the curve (AUC) of the receiver operating characteristic (ROC) were calculated. Results: The R-way system had a slightly lower specificity (94.5%) than conventional colposcopy (96.0%) for CIN2+ detection (P=0.181). However, the sensitivity (77.8%) was significantly higher than with the conventional colposcopic method (46.6%) (${\chi}^2=64.351$, P<0.001). In addition, the AUC of the ROC for CIN2+ detection using the R-way system (0.839) was larger than that with conventional colposcopy (0.731) (Z=4.348, P<0.001). If preliminary result had been drawn from cervical exfoliated cytology before colposcopy referral, combination of the R-way system with cytology could increase the sensitivity to 93.9% for CIN2+ detection (excluding ASCUS\LSIL), confirmed by multipoint biopsy or ECC. Conclusions: The diagnostic value of the R-way evaluation system is higher than that of conventional colposcopic evaluation in cervical cancer screening. Moreover, taking the ease of use and standardized quality control management into account, the R-way system is highly preferable.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3147-3153
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• 2016

Background: Many strategies are required for cervical cancer reduction e.g. provision of education cautious sexual behavior, HPV vaccination, and early detection of pre-invasive cervical lesions and invasive cancer. Basic health data for cervical cytology/ HPV DNA and associated factors are important to make an appropriate policy to fight against cervical cancer. Aims: To assess the prevalence of abnormal cervical cytology and/or HPV DNA and associated factors, including sexual behavior, among Bangkok Metropolitan women. Materials and Methods: Thai women, aged 25-to-65 years old, had lived in Bangkok for ${\geq}5$ years were invited into the study. Liquid-based cervical cytology and HPV DNA tests were performed. Personal data were collected. Main Outcomes Measures: Rates of abnormal cytology and/ or high-risk HPV (HR-HPV) and factors associated with abnormal test (s) were studied. Results: Abnormal cytology and positive HR-HPV were found in 6.3% (279/4442 women) and 6.7% (295/4428), respectively. The most common abnormal cytology was ASC-US (3.5%) while the most common HR-HPV genotype was HPV 16 (1.4%) followed by HPV 52 (1.0%), HPV 58 (0.9%), and HPV 18 and HPV 51 at equal frequency (0.7%). Both tests were abnormal in 1.6% (71/4428 women). Rates of HR-HPV detection were directly associated with severity of abnormal cytology: 5.4% among normal cytology and 13.0%, 30.8%, 40.0%, 39.5%, 56.3% and 100.0% among ASC-US, ASC-H, AGC-NOS, LSIL, HSIL, and SCC, respectively. Some 5% of women who had no HR-HPV had abnormal cytology, in which 0.3% had ${\geq}$ HSIL. Factors associated with abnormal cytology or HR-HPV were: age ${\leq}40$ years, education lower than (for cytology) or higher than bachelor for HR-HPV), history of sexual intercourse, and sexual partners ${\geq}2$. Conclusions: Rates for abnormal cytology and HR-HPV detection were 6.3% and 6.7% HR-HPV detection was directly associated with severity of abnormal cytology. Significant associated factors were age ${\leq}40$ years, lower education, history of sexual intercourse, and sexual partners ${\geq}2$.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5519-5525
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• 2013

Background: Cervical cancer is the second most common cancer in Thai women after breast cancer. Currently, the Papanicolaou (Pap) smear is the recommended procedure for cervical cancer screening in Thailand, but only a relatively small percentage of women follow this screening program. An alternative method to detect HPV genotypes associated with cervical cancer is self-sampling of urine, which is a more widely accepted method. Our study aimed to evaluate the prevalence of HPV in Thai women using urine and cervical swabs and prevalence of HPV in Thai men using urine samples. Materials and Methods: Tumorigenic HPV detection was accomplished by electrochemical DNA chip and PCR/direct sequencing. In addition to HPV prevalence, we report the concordance between different methods and sample types. One-hundred and sixteen women and 100 men were recruited. Histological examination revealed normal cytology in 52 women, atypical squamous cells of undetermined significance (ASCUS) in 9, low-grade squamous intraepithelial lesions (LSIL) in 24, and high-grade squamous intraepithelial lesions (HSIL) in 31. One-hundred men were classified as heterosexuals (n=45) and homosexuals (n=55). Results: The most prevalent HPV genotype in our study was HPV16. The HPV detection rate was generally lower in urine samples compared with cervical samples. Overall, there was good agreement for the detection of carcinogenic HPV from female cervical samples between the DNA chip and PCR/sequencing, with 88.8% total agreement and a kappa value of 0.76. In male urine samples, the level of agreement was higher in heterosexuals compared with homosexuals. Conclusions: Further improvement is required to increase an overall yield of HPV DNA detection in urine samples before clinical application of a urine-based HPV screening program. The electrochemical DNA chip test is a promising technique for carcinogenic HPV detection.

• The Korean Journal of Cytopathology
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• v.19 no.2
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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.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.259-266
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• 2015

Cervical cancer is the third most common cancer among women worldwide. Cervical cancer is significantly associated with human papillomavirus (HPV) infection. The prevalence of HPV infection is influenced by geography, immune status, sexual history and genetic factors. For example, geographically, HPV prevalence varies from 1.5% to 39%. However, little is known about the relationship between HPV prevalence and age. An analysis of HPV prevalence by age will help determine when high-risk groups are exposed to HPV. Such an analysis could also demonstrate a correlation between specific HPV genotypes and age. In addition, the analysis might clarify the optimum age for using vaccines. In this study, HPV prevalence and genotype distribution among Korean and Chinese women are analyzed by age. The REBA HPV-ID$^{(R)}$ assay (YD diagnostics, Yong-in, Republic of Korea) was used for detecting HPV genotypes in uterine cervical liquid-based cytology samples from 533 women from Korea and 324 from East China (Western Shandong province. Women with severe dysplasia such as SCC (Squamous cell carcinoma) and HSIL (High-grade squamous intraepithelial lesion) groups were primarily in their 40s and 50s, whereas women with mild and moderate dysplasia (ASCUS and LSIL groups) were primarily in their 30s and 40s. Women with HPV genotype 16 and 18 infections were primarily in their 40s. The results suggest that HPV infection is associated with certain age groups in the Korean population.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.169-180
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• 1999

Background: Uterine cervical cancer is the most common malignant tumor of the women in Korea. This study was undertaken to evaluate the usefulness of the cervicography as a screening test of cervical cancer. Materials and Methods: Cervicography was taken from 482 women at department of obstetrics and gynecology, at Yeungnam University Hospital from March 1, 1998 to October 31, 1999. Of the 482 women, 172 women were exc1uded from the study for various reasons, and 310 women completed the study. Three-hundred and ten women had cervical cytology (Papanicolaou smear), cervicography and colposcopy, and punch biopsy was undertaken if any of the test result was abnormal. Results: The most common age group was 35-39, and 40-44, 45-49 in order and most common reason for having a screening test was regular check for cervical cancer. The mean duration from the last Pap smear was 17.1 months, and 64 women(20.4%) never had any prior screening tests. Of the 310 women, 254 women were categorized as normal or having benign disease such as cervicitis, erosion or metaplasia. Biopsy was taken from 56 patients and the results were 26 chronic cervicitis, 4 mild dysplasia, 6 moderate dysplasia, 2 severe dysplasia, 14 carcinoma in situ and 4 invasive carcinoma. The results of cytology and cervicography were well correlated(p<0.05). The sensitivity and specificity of cytology were 86.7% and 76.9%, respectively and the sensitivity and specificity of cervicography were 56.7% and 96.2%, respectively. False negative rate of cervicography(43.3%) was much higher than those of cytology(13. 3%) (p<0.05), but false positive rate of cervicography(3.8%) was much lower than that of cytology(23.1%) (p<0.05). Conclusion: It seems inappropriate to use cervicography as a single screening test for cervival cancer, but it may be an effective complementary test for cytology to lower the false negative rate of cytology.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.3
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• pp.132-139
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• 2015

Recently, $p16^{INK4a}$/Ki-67 dual immunostaining has been introduced as a new biomarker protocol for early detection of uterine cervical dysplasia and cancer in liquid-based cytology (LBC). We performed the $p16^{INK4a}$/Ki-67 dual immunostaining using a CINtec$^{(R)}$ PLUS kit in a total of 109 LBC cases of cervicovaginal smear and compared its results with those from LBC, HPV hybrid capture II (HC II) test and histological diagnosis. Expression of $p16^{INK4a}$ and Ki-67 was significantly associated with cases of LSIL or higher in cytological diagnosis and cases of cervical intraepithelial neoplasia (CIN) 1 or higher in histological diagnosis (p<0.001 and p<0.001, respectively). Among forty-six cases of atypical squamous cells of undetermined significance (ASCUS) in LBC, $p16^{INK4a}$ and Ki-67 was expressed in 31 (67.4%), which were positively associated with cases of CIN I lesion or higher in histology. The sensitivity of $p16^{INK4a}$/Ki-67 dual immunostaining for finding lesions of CIN 1 or higher was 89.0%, which was higher than LBC. The specificity was 73.5%, which was higher than that of the HC II test. Based on these results, the $p16^{INK4a}$/Ki-67 dual immunostaining method can be a useful diagnostic marker for improving the sensitivity of LBC and the specificity of HC II test.