• YAKHAK HOEJI
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• v.46 no.6
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• pp.426-432
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• 2002

Cervical cancer is one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papilloma viruses (HPV type 16 and 18) and cervical cancer has been well known. An extract of Saururus chinensis, named as PE-46, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. PE-46 inhibited the proliferation of human cervical cancer cell lines in a dose response manner. PE-46 also inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, PE-46 inhibited the in vitro binding of E7 and Rb which is essential tumor suppressor for the control of cell cycle. The levels of mRNA for E6 and E7 were also decreased by PE-46. SiHa cells treated with PE-46 induced G0/G1 arrest, resulting in inhibition of growth. Our study showed that the PE-46 can inhibit the cervical carcinomas via both inhibition of bindings between oncogenes and tumor suppressors, and inhibition of G1longrightarrowS transition. PE-46 inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus could be used as a putative modulating agent for the treatment of cervical carcinomas caused by HPV.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4477-4487
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• 2015

In this review we summarize the results of studies employing high-throughput methods of profiling of HPV-associated cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancers at key intracellular regulatory levels to demonstrate the unique identity of the landscape of molecular changes underlying this oncopathology, and to show how these changes are related to the 'natural history' of cervical cancer progression and the formation of clinically significant properties of tumors. A step-wise character of cervical cancer progression is a morphologically well-described fact and, as evidenced by genome-wide screenings, it is indeed the consistent change of the molecular profiles of HPV-infected epithelial cells through which they progressively acquire the phenotypic hallmarks of cancerous cells. In this sense, CIN/cervical cancer is a unique model for studying the driving forces and mechanisms of carcinogenesis. Recent research has allowed definition of the whole-genome spectrum of both random and regular molecular alterations, as well as changes either common to processes of carcinogenesis or specific for cervical cancer. Despite the existence of questions that are still to be investigated, these findings are of great value for the future development of approaches for the diagnostics and treatment of cervical neoplasms.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4167-4175
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• 2013

A najor current challenge and constraint in cervical cancer research is the development of vaccines against human papilloma virus (HPV) epitopes. Although many studies are done on epitope identification on HPVs, no computational work has been carried out for high risk forms which are considered to cause cervical cancer. Of all the high risk HPVs, HPV 16, HPV 18 and HPV 45 are responsible for 94% of cervical cancers in women worldwide. In this work, we computationally predicted the promiscuous epitopes among the E6 proteins of high risk HPVs. We identified the conserved residues, HLA class I, HLA class II and B-cell epitopes along with their corresponding secondary structure conformations. We used extremely precise bioinformatics tools like ClustalW2, MAPPP, NetMHC, Epi,Jen, EpiTop 1.0, ABCpred, BCpred and PSIPred for achieving this task. Our study identified specific regions 'FAFR(K)DL' followed by 'KLPD(Q)LCTEL' fragments which proved to be promiscuous epitopes present in both human leukocyte antigen (HLA) class I, class II molecules and B cells as well. These fragments also follow every suitable character to be considered as promiscuous epitopes with supporting evidences of previously reported experimental results. Thus, we conclude that these regions should be considered as the important for design of specific therapeutic vaccines for cervical cancer.

• Korean Journal of Microbiology
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• v.42 no.3
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• pp.177-184
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• 2006

This study was performed to evaluate the prevalence of high risk Human papilloma virus (HPV), Herpes simplex virus type 1, 2 (HSV-1,2), Hepatitis B virus (HBV) and Human Immuno deficiency virus (HIV) infection with sexual transmitted viral diseases in Busan during 2004 to 2005. six hundred seventy four samples of cervical swabs were tested for sexually transmitted viral diseases. Among the isolated viruses, 23 (3.4%) samples were HPV and 3 (0.4%) and 9 (1.3%) samples were HSV 1 and 2, respectively. Among the 586 serum samples tested for viruses, HSV IgM 121 (3.6%), HSV-1 IgG 487 (83.1%), HSV-2 IgG 135 (23.0%), HBsAg 26 (4.4%), HBeAg 7 (1.2%), and HIV (0%) types were found. HPV genotypes were detected in 16 patients, of which 13 cases were high risk type HPV, 3 cases were low risk type HPV, and multi infection were detected in 7 cases. In the age distribution of the patients, 7.2% of infection tested from cervical swabs occurred in under the age of 20, while 100% of infection was found to occur in those who were 40 years old or older in the serum samples. The outbreak pattern in their occupations was found to be the highest at the health organization (amusement quarter) for the cervical swabs, and at infirmary (commercial sex worker) for the serum samples, respectively.

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

• KSBB Journal
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• v.16 no.6
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• pp.579-591
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• 2001

The cell growth inhibitor effect of cervical cancer cells was investigated by liposome mediated transfection (pRcCMVp53/lipofectin) and by transfection using adenovirus (AdCMVp57). The papilloma virus cancer cell lines we used in this study were HPV16 positive, having inhibiter gene, wild p53 gene, CaSki, SiHa, HPV18 positive HeLa, HeLaS3 and HPV negative C33A, HT3. LacZ gene of E.coli was used as the marker gene for the transfection efficiency. The effect on the inhibition of tumor cell growth was measured by cell count and cell viability though ELISA analysis and MTT assay. The inhibition of tumor cell growth was confirmed by measuring each assay for six days, comparing with the normal control cell growth. The cell growth of cervical cancer calls by transfection was significantly reduced and showed tittle differences among the cell lines. To eliminate the potential problem of Ad(adenovirus) contamination during rAAV production, rAAV can be produced by a triple transfection of vector plasmic, packaging plasmid, and adenovirus helper plasmid. To examine the helper functions of Ad plasmids on the production of rAAV vector, we carried out cotransfection of three plasmids, AAV vector, packaging construct, and Ad helper plasmids. The optimized transfection condition for calcium phosphate method is 25ug of total DNA per 10-cm-diameter plate of 293 cell. We found that rAAV yields peaked at 48hr after Ad infection. The titer of rAAV was measured by the dot blot analysis to measure the number of particles/ml based on the quantification of viral DNA. Recent1y, Kombucha(fungi) was identified as a very potent antileukefic agent. In the present study, effect of natural toxin(plankton) and Kombucha is PSP(GTXI-3, neoSTX), on various MTT assay cervical cancer cell line. Toxin(GTX 1-3, neoSTX) also inhibited the proliferation in primary cervical cancer calls in a dose-dependent toxin concentration. These results showed that toxin was very potent in inhibiting the proliferation of cervical cancer calls in vitro. Toxins and Kombuoha exhibited a dose dependent inhibition of cellular proliferation in cancer cell line.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6429-6438
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• 2015

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles. The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned to evaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. The study was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minor gynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attending the cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) using L1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures. Differences in proportions were tested using Pearson's Chi-square test with Odds ratio (OR) and 95% confidence interval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype (OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes was observed in women with normal, precancerous and cervical cancerous lesions among ${\leq}35$ or >35 years of age groups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers (OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervical cancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) and GSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive non smokers. The results demonstrate that the GST null genotypes were alone not associated with the development of cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.

• 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.13 no.4
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• pp.1151-1158
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• 2012

High-risk human papillomavirus (HPV) genotypes are the major cause of cervical cancer. Hence, HPV genotype detection is a helpful preventive measure to combat cervical cancer. Recently, several HPV detection methods have been developed, each with different sensitivities and specificities. The objective of this study was to compare HPV high risk genotype detection by an electrochemical DNA chip system, a line probe assay (INNO-LiPA) and sequencing of the L1, E1 regions. A total of 361 cervical smears with different cytological findings were subjected to polymerase chain reaction-sequencing and electrochemical DNA chip assessment. Multiple infections were found in 21.9% (79/361) of the specimens, most prevalently in 20-29-year olds while the highest prevalence of HPV infection was found in the 30-39-year age group. The most prevalent genotype was HPV 16 at 28.2% (138/489) followed by HPV 52 at 9.6% (47/489), with the other types occurring at less than 9.0%. The electrochemical DNA chip results were compared with INNO-LiPA and sequencing (E1 and L1 regions) based on random selection of 273 specimens. The results obtained by the three methods were in agreement except for three cases. Direct sequencing detected only one predominant genotype including low risk HPV genotypes. INNO-LiPA identified multiple infections with various specific genotypes including some unclassified-risk genotypes. The electrochemical DNA chip was highly accurate, suitable for detection of single and multiple infections, allowed rapid detection, was less time-consuming and was easier to perform when compared with the other methods. It is concluded that for clinical and epidemiological studies, all genotyping methods are perfectly suitable and provide comparable results.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.107-110
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• 2014

Background: Increasing uptake of human papillomavirus (HPV) vaccine should be a priority in developing countries since they suffer 88% of the world's cervical cancer burden. In many countries studies show that age at vaccination is an important determinate of parental acceptability. This study explores parental preferences on age-to-vaccinate for adolescent school-going girls. Materials and Methods: The sample was selected using a two-stage probability proportional to size cluster sampling methodology. Questionnaires were sent home with a random sample of 800 adolescent girls attending 12 schools in Mysore to be completed by parents. Descriptive statistics including frequencies, percentages and proportions were generated for independent variables and bivariate analyses (Chi square test) were used to assess the relationship between independent and appropriate age-to-vaccinate. Results: HPV vaccination acceptability was high at 71%. While 5.3% of parents felt girls should be vaccinated by 10 years or younger; 38.3% said 11-15 years; 14.8% said 16-18 years; 5.8% suggested over 19 years; and 33% didn't know. Only 2.8% of parents would not vaccinate their daughters. Conclusions: Delaying HPV vaccination until later ages may signifivantly increase uptake of the HPV vaccine in India.