• BMB Reports
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• 제34권1호
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• pp.80-84
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• 2001

The human papillomavirus E7 protein can form a specific complex with a retinoblastoma tumor suppressor gene product (p105-Rb) that results in the release of the E2F transcription factor, which is critical for the growth-deregulation and transforming properties of the viral E7 oncoprotein. In an attempt to apply interaction between the E7 oncoprotein and a target cellular protein Rb for an in vitro screening system for drugs against human papillomavirus infection, we primarily investigated the E7Rb binding through a pull down assay and enzyme-linked immunosorbent assay. The pull down assay showed that both glutathione S-transferase-tagged E7 and His-tagged E7 immobilized on resins specifically produced complexes with bacterially expressed Rb in a dose-dependent manner, as determined by immunoblot analyses. This result coincided with that of an enzyme-linked immunosorbent assay, which is a useful system for the mass screening of potential drugs. Taken together, this screening system (based on the interaction between E7 and Rb) can be a promising system in the development of drugs against cervical cancers caused by human papillomavirus infection.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6697-6701
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• 2014

Background: In the etiology of cervical cancer not only HPV infection is important, but also other factors such as demographic influences andsexual and reproductive health attitudes, as well as others related to preventive measure usage (or non usage). The aim of this study was to examine factors associated with cervical dysplasia in asymptomatic women who were examined by routine cytology and cervical biopsy for early detection of cervical cancer. Materials and Methods: Socio-demographic and other characteristics were obtained from medical files of 85 examinees with pathologic cytologic findings (Pap test) and histopathologic (HP) findings after biopsy. Results: ccording to the Pap test result, a greater probability for development of cervical dysplasia was noted with examinees having a larger number of sexual partners (OR= 5.01, 95% CI 1.04-24.10), and those who are afraid of the Pap finding. Risk factors for development of cervical dysplasia according to the bioptic finding were early beginning with sexual activities, presence of any STD in personal medical history and fear of the Pap test finding. Conclusions: The only risk factor found to be important for both methods was fear of the Pap testing finding.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.4867-4871
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• 2012

Cervical cancer is a leading cause of morbidity and mortality in women worldwide. Although the human papillomavirus (HPV) is considered the major causative agent of cervical cancer, yet the viral infection alone is not sufficient for cancer progression. The etiopathogenesis of cervical cancer is indeed complex; a precise understanding of the complex cellular/molecular mechanisms underlying the initiation, progression and/or prevention of the uterine cervix is therefore essential. Autophagy is emerging as an important biological mechanism in targeting human cancers, including cervical cancer. Furthermore, autophagy, a process of cytoplasm and cellular organelle degradation in lysosomes, has been implicated in homeostasis. Autophagic flux may vary depending on the cell/tissue type, thereby altering cell fate under stress conditions leading to cell survival and/or cell death. Autophagy may in turn govern tumor metastasis and subsequent carcinogenesis. Inflammation is a known hallmark of cancer. Vascular insufficiency in tumors, including cervical tissue, leads to depletion of glucose and/or oxygen perturbing the osmotic mileu causing extracellular acidosis in the tumor microenvironment that may eventually result in autophagy. Thus, targeted manipulation of complex autophagic signaling may prove to be an innovative strategy in identification of clinically relevant biomarkers in cervical cancer in the near future.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1177-1180
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• 2014

Background: Anogenital warts (AGWs) are common results of sexually transmitted infection (STI). Human papillomavirus (HPV) types 6 and 11, which are non-oncogenic types, account for 90% of the clinical manifestations. Although the quadrivalent HPV vaccine has been launched, AGW remains prevalent in some countries and shows association with abnormal cervical cytology. Objectives: To study the prevalence of abnormal cervical cytology (low grade squamous intraepithelial lesions or worse; LSIL+) in immunocompetent Thai women newly presenting with external AGWs. Materials and Methods: Medical charts of all women attending Siriraj STI clinic during 2007-2011 were reviewed. Only women presenting with external AGWs who were not immunocompromised (pregnant, human immunodeficiency virus positive or being on immunosuppressant drugs) and had not been diagnosed with cervical cancer were included into the study. Multivariate analysis was used to determine the association between the characteristics of the patients and those of AGWs and LSIL+. Results: A total of 191 women were eligible, with a mean age of $27.0{\pm}8.9$ years; and a mean body mass index of $20.6{\pm}8.9kg/m^2$. Half of them finished university. The most common type of AGWs was exophytic (80.1%). The posterior fourchette appeared to be the most common affected site of the warts (31.9%), followed by labia minora (26.6%) and mons pubis (19.9%). The median number of lesions was 3 (range 1-20). Around 40% of them had recurrent warts within 6 months after completing the treatment. The prevalence of LSIL+ at the first visit was 16.3% (LSIL 12.6%, ASC-H 1.1%, HSIL 2.6%). After adjusting for age, parity and miscarriage, number of warts ${\geq}5$ was the only factor associated with LSIL+(aOR 2.65, 95%CI 1.11-6.29, p 0.027). Conclusions: LSIL+ is prevalent among immunocompetent Thai women presenting with external AGWs, especially those with multiple lesions.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2317-2322
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• 2015

Background: Despite the increasing number of screening examinations performed for cervical cancer utilizing the Papanicolaou smear test (Pap test), few studies have examined whether this strategy is cost-effective in Korea. Objective: This study was conducted to evaluate the cost-effectiveness of cervical cancer screening strategies incorporating the Pap test based on age at the start and end of screening as well as screening interval. Materials and Methods: We designed four alternative screening strategies based on patient age when screening was started (20 or 30 years) and discontinued (lifetime, 79 years). Each strategy was assessed at screening intervals of 1, 2, 3, or 5 years. A Markov model was developed to determine the cost-effectiveness of the 16 possible cervical cancer screening strategies, and this was evaluated from a societal perspective. The main outcome measures were average lifetime cost, incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Results: Compared with various strategies comprising younger starting age, discontinuation age, and longer screening intervals, strategies employing annual screening for cervical cancer starting at a target age of 30 years and above were the most cost-effective, with an ICER of 21,012.98 dollars per QALY gained (with a Korean threshold of 30,000,000 KRW or US$27,272). Conclusions: We found that annual screening for cervical cancer beginning at a target age of 30 years and above is most cost-effective screening strategy. Considering the potential economic advantages, more intense screening policies for cervical cancer might be favorable among countries with high rates of cervical cancer and relatively low screening costs.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4149-4154
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• 2016

Background: Cervical carcinoma is one of the main causes of mortality in women worldwide as well as in India. It occurs as a result of various molecular events that develop from the combined influences of an individual's genetic predisposition and external agents such as smoking and menstrual hygiene, for example. However, infection with human papillomavirus (HPV) is the established major risk factor. The aim of the current study was to investigate p16 CpG island methylation and establish any correlation with mRNA expression in north Indian population. Materials and Methods: We analyzed 196 woman volunteer out of which 98 were cases and 98 healthy controls. For the analysis of methylation pattern, DNA extracted from blood samples was modified with a bisulfate kit and used as template for methylation specific PCR (MSP). Quantitative real-time PCR (QRT-PCR) was performed to check mRNA expression. Results: Correlation between methylation status of p16 gene and poor menstrual hygiene was significant (p=0.006), high parity cases showed methylation of p16 gene (p=0.031) with increased risk up to 1.86 times for cervical cancer and smoking was a strong risk factor associated with cervical cancer. We analyzed methylation pattern and found 60.3% methylation in cases with low mRNA expression level (0.014) as compare to controls (1.24). It was also observed that promoter methylation of p16 gene was significantly greater in FIGO stage III. Conclusions: We conclude that p16 methylation plays an important role in cervical cancer in the north Indian population and its methylation decreases mRNA expression. It can be used as an important and consistent blood biomarker in cervical cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6557-6559
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• 2015

Background: Cervical human papillomavirus (HPV) infection among young women (20-25 years of age) is common and normally transient. There are growing concerns that referral to a colposcopy clinic may lead to unnecessary treatment with an increased risk of obstetric complications. Therefore, the purpose of this study was to determine the level of intervention for cervical abnormalities in this age group of the Northern Ireland population. Materials and Methods: A review of all serial new patients under 25 years of age, who were referred to colposcopy clinics in Northern Ireland between January 1, 2009 to June 30, 2009 formed the basis of this study. Results: During the study period, a total of 4,767 women under 25 years of age were screened. Two-hundred-and-thirty-four (4.9%) cases were referred to the colposcopy clinics. The cervical cytology results were: high-grade abnormality in 35%, and low-grade abnormality in 31% of these cases. One-hundred-and-seventy-eight (76%) of the referred women received at least one treatment. One-hundred-and-twenty-one of 234 (51.5%) women underwent an excisional treatment with histology showing the presence of high-grade abnormalities (CIN2-3) in 52%, CIN1 in 28%, and Koilocytosis or normal tissue in 20% of this sub-group of cases. Conclusions: Screening women under the age of 25 years cause unnecessary referral for colposcopy. This may also result in considerable anxiety and psychosexual morbidity. It leads to an over-treatment with a potential of negative impact on the future pregnancy outcomes (including pre-term delivery, low birth weight, and pre-term premature rupture of membranes).

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6375-6379
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• 2015

Background: Cervical cancer is the second most common cancer in women worldwide, with about 500,000 new cases and 270,000 deaths each year. Globally, it is estimated that over one million women currently have cervical cancer, most of whom have not been diagnosed, or have no access to treatment that could cure them or prolong their lives. In the United Arab Emirates (UAE) cervical cancer is the third most common cancer in women. Materials and Methods: A population-based cross-sectional retrospective survey of cervical smear abnormalities was conducted in the Emirate of Abu Dhabi, UAE, from January 2013 to December 2013 by collecting consecutive liquid-based cytology samples from the Department of Pathology at the SKMC Hospital in Abu Dhabi city. Results: The total number of women screened for cervical cancer for the year 2013 at SKMC was 4,593, with 225 (4.89%) abnormal smears. The majority of the abnormal smear results were atypical squamous cells of undetermined significance (ASCUS) 114 (2.48%). This study showed 60% increase in the rate of abnormal cervical smears in the UAE over the last 10 years. In this study the highest incidence of high grade abnormalities were seen in women above the age of 61years (1.73%), this might be due to the fact that this group of women missed the chance of screening of cervical cancer earlier in their lives or could be explained by the well-known second peak of HPV infection seen in many prevalence studies. Conclusions: We conclude that the rate of abnormal cervical smear in the screened Abu Dhabi women is not different from the rate in developed countries. A notable increase in both low and high grade abnormalities has occurred within the last decade.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7357-7362
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• 2014

Interleukin-6 (IL-6), a central proinflammatory cytokine, maintains immune homeostasis and also plays important roles in cervical cancer. Therefore, we aimed to evaluate any associations of IL-6 gene polymorphisms at positions -174 and -572 with predisposition to cervical cancer in a Chinese population. The present hospital-based case-control study comprised 518 patients with cervical cancer and 518 healthy controls. Polymorphisms of the IL-6 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients with cervical cancer had a significantly higher frequency of the IL-6 -174 CC genotype [odds ratio (OR) =1.52, 95% confidence interval (CI) = 1.06-2.19; p=0.02], IL-6 -572 CC genotype (OR =1.91, 95% CI = 1.16-3.13; p=0.01) and IL-6 -174 C allele (OR =1.21, 95% CI = 1.02-1.44; p=0.03) compared to healthy controls. When stratifying by the FIGO stage, patients with III-IV cervical cancer had a significantly higher frequency of IL-6 -174 CC genotype (OR =1.64, 95% CI =1.04-2.61; p=0.04). The CC genotypes of the IL-6 gene polymorphisms at positions -174 and -572 may confer a high risk of cervical cancer. Additional studies with detailed human papillomavirus (HPV) infection data are warranted to validate our findings.

• 한국치위생학회지
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• 제15권3호
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• pp.523-529
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• 2015

Objectives: Oropharynx tumors(oral cancer), are caused by tobacco, alcohol consumption, and high-risk human papillomavirus(HPV) infection. Oral squamous cell carcinoma(OSCC) is the most common type of oral cancer and frequently arises from the mucosa of the oropharynx and oral cavity. Despite advances in the diagnosis and treatment(chemotherapy, radiotherapy, and surgery) of oral cancer, over the past two decades, the overall survival rates remains at about 60%. Methods: We pretreated HSC-2 cells with various doses of exposed the cells to eugenol and then we measured cell viability by MTT assay. Results: Cell proliferation was markedly inhibited after eugenol treatment compared to the control. The majority of HSC-2 cells in the control groups showed normal morphology with round regular nuclei. In contrast, apoptotic bodies were seen in the 0.5 mM, 1 mM, 2 mM group. However, the pretreatment with eugenol increased HSC-2 cells apoptosis according to dose-dependency. PI staining quantitatively confirmed the anti-apoptotic effects of propofol. The expression levels of cleaved caspase 3, and Bak significantly increased in HSC-2 cells. Conclusions: These findings indicate that eugenol could be a potential anti-cancer agent for human OSCC and provide valuable data for the development of a novel anticancer strategy.