• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.14
• /
• pp.5749-5754
• /
• 2015

Cervical carcinoma is the main cause of cancer-related mortality in women and is correlated with more than 15 risk cofactors, including infection of cervical cells with high-risk types of HPV (hrHPV). Indeed, both aberrant methylation of the RASSF1A promoter and hrHPV infection are often observed in cervical carcinomas. The purpose of our meta-analysis was to evaluate the role of RASSF1A promoter methylation and hrHPV infection in cervical cancer. Our meta-analysis involved 895 cervical cancer patients and 454 control patients from 15 studies. Our results suggested that RASSF1A promoter hypermethylation increased the risk of cervical cancer (OR=9.77, 95%CI=[3.06, 31.26], P=0.0001, $I^2=78%$). By grouping cases according to cancer subtypes, we found that HPV infection was higher in cervical squamous cell carcinomas (SCCs) than in cervical adenocarcinomas/adenosquamous cancers (ACs/ASCs) (OR=4.00, 95%CI=[1.41, 11.30], P=0.009, $I^2=55%$). Interestingly, HPV infection tended to occur in cervical cancers with relatively low levels of RASSF1A promoter methylation (OR=0.59, 95%CI=[0.36, 0.99], P=0.05, I2=0%). Our study provides evidence of a possible interaction between HPV infection and RASSF1A promoter methylation in the development of cervical cancers.

• The Korean Journal of Cytopathology
• /
• v.15 no.1
• /
• pp.17-27
• /
• 2004

To investigate a population-based survey of the prevalence of human papillomavirus (HPV) infection in South Korea, we performed Papanicolaou smears and tests for HPV DNA and anti-HPV antibody detection in 909 sexually active general women (age range; 20-74 years, median 44 years) who were randomly selected residents from S district of Busan City. The presence of DNA of 36 different HPV types was detected by means of a GP 5+/6+ primer-mediated PCR enzyme immunoassay in cervical exfoliated cells, and IgG antibodies against L1 virus-like particles (anti-VLPs) of 5 HPV types 16, 18, 31, 33, and 58 were tested by means of enzyme linked immunoassay. The incidence of cytologic abnormality was 5.2% in Pap smear. The positive rate of HPV DNA was 10.4%, high in young women younger than 35 years old and proportionally increased according to the cytologic grades. The most often found HPV type was HPV 70, followed by HPV 16 and 33, and high-risk HPV types were more frequent in women younger than 35 years old. The most common HPV type in abnormal cytologic smears was HPV 16, followed by HPV 58 and 66. Anti-VLPs was positive in 19.7% and the frequent anti-VLPs type was against HPV 18, followed by HPV 31 and 16. The concordance between the markers for each specific HPV type was noted in 10 women and HPV 16 was the most frequent one. The incidence of multiple HPV infection was 18.9% and that of multiple anti-VLPs antibodies was 31%. Among 103 self-reported virgins, 4.9% had anti-VLP antibodies.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.14
• /
• pp.5843-5846
• /
• 2015

Background: Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. Materials and Methods: A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chisquare test was used to test the differences of PAX1 methylation or HPV infection between groups. Results: The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. Conclusions: The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.18
• /
• pp.7951-7954
• /
• 2014

Background: To evaluate the cervical pathology of cytology-negative/high-risk human papillomavirus (HR-HPV) positive-women. Materials and Methods: This study recruited 4,583 women aged 30-70 years who had undergone cervical screening by liquid-based cytology and HR-HPV test (14 HR-HPV types) at Lampang Cancer Hospital during October 2012 to July 2013. Colposcopy was carried out in all women. Results: One hundred and ninety-two (4.19%) women were found to be cytology-negative/HR-HPV-positive. However, 23 cases were excluded because of incomplete information, leaving 169 women for further analyses. Of these 169, 45 (26.6%) were infected with HPV 16/18 and 49 (29.0%) with multiple genotypes of HR-HPV. Nineteen of 169 (11.24%) women were found to have CIN 2-3. No women in the present study had AIS or invasive cervical lesions. Prevalence of CIN 2-3 among women infected with HPV 16/18 was 15.6% which was higher than the 9.68% in those with non-HPV 16/18 oncogenic types. Conclusions: Overall, 11% of cytology-negative/HR-HPV-positive women had significant cervical lesions. Risk of harboring such lesions was substantially increased among those who were HPV 16/18 positive.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.3
• /
• pp.1643-1647
• /
• 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
• /
• v.15 no.2
• /
• pp.651-656
• /
• 2014

Background: Cervical cancer is the third commonest type of cancer among women in Malaysia. Our aim was to determine the distribution of human papilloma virus (HPV) genotypes in cervical cancer in our multi-ethnic population. Materials and Methods: This was a multicentre study with a total of 280 cases of cervical cancer from 4 referral centres in Malaysia, studied using real-time polymerase chain reaction (qPCR) detection of 12 high risk-HPV genotypes. Results: Overall HPV was detected in 92.5% of cases, in 95.9% of squamous cell carcinomas and 84.3%of adenocarcinomas. The five most prevalent high-risk HPV genotypes were HPV 16 (68.2%), 18 (40%), 58 (10.7%), 33 (10.4%) and 52 (10.4%). Multiple HPV infections were more prevalent (55.7%) than single HPV infections (36.8%). The percentage of HPV positive cases in Chinese, Malays and Indians were 95.5%, 91.9% and 80.0%, respectively. HPV 16 and 18 genotypes were the commonest in all ethnic groups. We found that the percentage of HPV 16 infection was significantly higher in Chinese (75.9%) compared to Malays (63.7%) and Indians (52.0%) (p<0.05), while HPV 18 was significantly higher in Malays (52.6%) compared to Chinese (25.0%) and Indians (28%) (p<0.05). Meanwhile, HPV 33 (17.9%) and 52 (15.2%) were also more commonly detected in the Chinese (p<0.05). Conclusions: This study showed that the distribution of HPV genotype in Malaysia is similar to other Asian countries. Importantly, we found that different ethnic groups in Malaysia have different HPV genotype infection rates, which is a point to consider during the implementation of HPV vaccination.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8145-8147
• /
• 2016

Background: Atypical squamous cells of undetermined significance (ASCUS) feature a wide variety of cervical cells, including benign and malignant examples. The management of ASCUS is complicated. Guidelines for office gynecology in Japan recommend performing a high-risk human papillomavirus (HPV) test as a rule. The guidelines also recommend repeat cervical cytology after 6 and 12 months, or immediate colposcopy. The purpose of this study was to determine the clinical significance of ASCUS. Materials and Methods: Between January 2012 and December 2014, a total of 162 patients underwent cervical conization for cervical intraepithelial neoplasia grade 3 (CIN3), carcinoma in situ, squamous cell carcinoma, microinvasive squamous cell carcinoma, and adenocarcinoma in situ at our hospital. The results of cervical cytology prior to conization, the pathology after conization, and high-risk HPV testing were obtained from clinical records and analyzed retrospectively. Results: Based on cervical cytology, 31 (19.1%) of 162 patients were primarily diagnosed with ASCUS. Among these, 25 (80.6%) were positive for high-risk HPV, and the test results of the remaining 6 patients (19.4%) were uncertain. In the final pathological diagnosis after conization, 27 (87.1%) and 4 patients (12.9%) were diagnosed with CIN3 and carcinoma in situ, respectively. Conclusions: Although ASCUS is known as a low-risk abnormal cervical cytology, approximately 20% of patients who underwent cervical conization had ASCUS. The relationship between the cervical cytology of ASCUS and the final pathological results for CIN3 or invasive carcinoma should be investigated statistically. In cases of ASCUS, we recommend HPV tests or colposcopic examination rather than cytological follow-up, because of the risk of missing CIN3 or more advanced disease.

• Journal of Life Science
• /
• v.19 no.6
• /
• pp.765-769
• /
• 2009

Recent studies have reported that the distribution of HPV-16 sequence variation differs geographically, and more specifically that HPV-16 E6/E7 intratypic variants might carry a high risk for development of ICC (invasive cervical cancer) and CIN (cervical intraepithelial neoplasia) in a given population. To investigate the genetic diversities of HPV-16 E6/E7 oncogene by region, we collected nineteen HPV-16 isolates from sexually high-risk women in Busan, and analyzed the HPV-16 E6/E7 coding regions (nt 34 to 880) with HPV-16 E6/E7 specific PCR amplification. At the nucleotide levet eleven variants of the E6 genes and nine variants of the E7 genes were identified as follows: E6 T178G (n=l1), E6 T178A (n=l), E6 T350G (n=3), E6 A442C (n=2), E6 AI04T, E6 All1G, E6 C116T, E6 G145T, E6 T183G, E6 C335T, E6 G522C and E7 A647G (n=12), E7 A645C, E7 A777C, E7 G663A, E7 T732C, E7 T760C, E7 A775T, E7 T789C and E7 T795G, respectively. At the amino acid levet the isolated HPV-16 E6 and E7 genes showed eleven E6 variants: E6 D25E (n=12), E6 L83V (n=4), E6 E113D (n=2), E6 MIL, E6 Q3R, E6 P5S, E6 Q14H, E6 D25N, E6 127R, E6 H78Y, E6 C140S and three E7 variants: N29S (n=12), L28F, T72S. HPV16 E6 L83V, the dominant variant in the Caucasian population, showed relatively low frequencies in our study population. We elucidated that the dominant HPV-16 E6/E7 variants were HPV-16 E6 D25E (63.2%) and HPV-16 E7 N29S (63.2%), which were phylogenetically included in Asian lineage. Further study is needed to evaluate the risk of cervical cancer related HPV-16 E6/E7 intratypic variants in the Korean population.

• Journal of Microbiology and Biotechnology
• /
• v.25 no.7
• /
• pp.1163-1169
• /
• 2015

Poly-gamma-glutamic acid (γ-PGA) is a natural polymer that is synthesized by Bacillus species and has been reported to have antitumor activity. The aim of this study was to investigate the effect of γ-PGA on the treatment of vaginal intraepithelial neoplasia (VAIN). A retrospective observational study on γ-PGA therapy for biopsy-proven VAIN was conducted. The efficacy was assessed by evaluating the results of Pap cytology and the viral load of high-risk HPV at three time points: at enrollment, and at the first and second post-treatment visits. Of 17 patients treated with γ-PGA, only 12 patients who had a high-risk HPV infection were included in the analysis. Histology was VAIN1 in seven patients, VAIN2 in two patients, and VAIN3 in three patients. γ-PGA was administered for newly diagnosed VAIN in five (41.7%) patients and persistent VAIN in seven (58.3%) patients for the mean time of 4.5 months. At the first and second post-treatment visits, cytological regression was observed in five (41.7%) and six (50%) patients, respectively. Regarding the HPV load, the overall response rate was 66.7%, and the mean level was 670.6 ± 292.5 RLU at the first follow-up, which was lower than the initial viral load of 1,494.8 ± 434.5 RLU (p = 0.084). At the second follow-up, the overall response rate was 58.3%, and the mean viral load level was 924.2 ± 493.7 RLU. γ-PGA may be helpful for the cytological regression and reduction of viral load in patients with high-risk HPV-positive VAIN, suggesting that γ-PGA is a promising treatment option for primary or persistent VAIN.

• Women's Health Nursing
• /
• v.23 no.2
• /
• pp.126-134
• /
• 2017

Purpose: The purpose of this study was to identify impacts of HPV-related knowledge, attitude to HPV vaccination, and health beliefs on infection preventive behavioral intention targeting female university students. Methods: With correlational survey design, subjects of this study were 120 female students at universities located in B metropolitan city and G city. A total sample agreed to participate in the study. Data were analyzed using descriptive statistics, t-test, ANOVA, correlation, and stepwise multiple regression. Results: Attitude to HPV vaccination, experience of smoking, and HPV-related health beliefs were significant factors influencing the HPV-related infection preventive behavioral intention. These factors accounted for 19.0% of the HPV-related infection preventive behavioral intention. Conclusion: The most significant factor for HPV infection prevention was the attitude to HPV vaccination. These findings may be useful to develop strategies to improve the HPV infection preventive behavioral intention of the female university students who have a high risk of the HPV infection.