scholarly journals Promoter Methylation of p16INK4A, hMLH1, and MGMT in Liquid-Based Cervical Cytology Samples Compared with Clinicopathological Findings and HPV Presence

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Aris Spathis ◽  
Evaggelia Aga ◽  
Maria Alepaki ◽  
Aikaterini Chranioti ◽  
Christos Meristoudis ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Promoter Methylation ◽  
Methylation Status ◽  
Cervical Carcinogenesis ◽  
Hpv Dna ◽  
Molecular Events ◽  
Dependent Inactivation ◽  
Clinicopathological Findings ◽  
Hpv Types ◽  
Cervical Cancer Development

Cervical cancer is a common cancer inflicting women worldwide. Even though, persistent infection with oncogenic Human Papillomavirus (HPV) types is considered the most important risk factor for cervical cancer development, less than 5% of women with HPV will eventually develop cervical cancer supporting that other molecular events, like methylation-dependent inactivation of tumor suppressor genes, may cocontribute in cervical carcinogenesis. We analyzed promoter methylation of three candidate genes (p16, MGMT, and hMLH1) in 403 liquid-based cytology samples. Methylation was commonly identified in both benign and pathologic samples and correlated with higher lesion grade determined by cytological, colposcopical, or histological findings, with HPV DNA and mRNA positivity of specific HPV types and p16INK4Aprotein expression. Overall accuracy of methylation is much lower than traditional diagnostic tests ranking it as an ancillary technique with more data needed to identify the exact value of methylation status in cervical carcinogenesis.

scholarly journals Human Papillomavirus and Cervical Cancer

2003 ◽  
Vol 16 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Eileen M. Burd
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Precancerous Lesions ◽  
Molecular Techniques ◽  
Hpv Dna ◽  
Molecular Events ◽  
Hpv Types ◽  
Cervical Cells ◽  
High Risk Hpv

SUMMARY Of the many types of human papillomavirus (HPV), more than 30 infect the genital tract. The association between certain oncogenic (high-risk) strains of HPV and cervical cancer is well established. Although HPV is essential to the transformation of cervical epithelial cells, it is not sufficient, and a variety of cofactors and molecular events influence whether cervical cancer will develop. Early detection and treatment of precancerous lesions can prevent progression to cervical cancer. Identification of precancerous lesions has been primarily by cytologic screening of cervical cells. Cellular abnormalities, however, may be missed or may not be sufficiently distinct, and a portion of patients with borderline or mildly dyskaryotic cytomorphology will have higher-grade disease identified by subsequent colposcopy and biopsy. Sensitive and specific molecular techniques that detect HPV DNA and distinguish high-risk HPV types from low-risk HPV types have been introduced as an adjunct to cytology. Earlier detection of high-risk HPV types may improve triage, treatment, and follow-up in infected patients. Currently, the clearest role for HPV DNA testing is to improve diagnostic accuracy and limit unnecessary colposcopy in patients with borderline or mildly abnormal cytologic test results.

scholarly journals The Value and Clinical Significance of ZNF582 gene Methylation in the Diagnosis of Cervical Cancer

2020 ◽  
Author(s):  
Chunhe Zhang ◽  
Shaowei Fu ◽  
Luyue Wang ◽  
Fang Wang ◽  
Dan Wu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Mrna Expression ◽  
Promoter Methylation ◽  
Zinc Finger Protein ◽  
Methylation Status ◽  
Cervical Lesions ◽  
Gene Methylation ◽  
Methylation Rate ◽  
Specificity And Sensitivity ◽  
Cancer Tissues

Abstract Background This study aimed to determine whether ZNF582 gene methylation and tissue protein expression can be used as a tool with high sensitivity and specificity for cervical cancer screening. We analyzed the correlation between promoter methylation of the zinc finger protein 582 (ZNF582) gene and cervical cancer and high risk HPV16/18 infection. Methods Tissue samples of normal cervical or chronic cervicitis (n=51), CIN (cervical intraepithelial neoplasia) (n=35), and cervical carcinoma (n=68) were tested for HPV16/18 infection by polymerase chain reaction (PCR). We also detected the methylation status of the ZNF582 gene promoter in the same tissues by methylation specific PCR (MSP), then analyzed the correlation between ZNF582 promoter methylation and HPV16/18 infection. Immunohistochemistry was used to analyze ZNF582 gene expression in 152 cervical tissues. We detected ZNF582 mRNA expression in cervical tissues (including cancer and non-cancer) by real-time fluorescence quantitative PCR (qRT-PCR).Results Among 93 high grade cervical lesions (CINII and above) and cervical cancer samples, 57 cases were positive for HPV16/18 infection and 36 cases were negative. ZNF582 gene methylation occurred in 9 out of 51 cases in normal cervical tissues (17.6%), 16 of 35 cases in CIN tissues (45.7%), and 50 of 68 cases in cervical cancer (73.5%). The differences in methylation rate of the three groups were statistically significant (P<0.05). The ZNF582 methylation rate in the positive HPV16/18 infection group was 73.7%, while the negative group was 63.9%. Compared with normal tissues, ZNF582 protein was highly expressed in cervical cancer tissues, but mRNA expression was low.Conclusion While ZNF582 protein is highly expressed in cervical cancer tissues, it was not sufficient for use as a standard for cervical cancer staging. On the other hand, ZNF582 promoter methylation had high specificity and sensitivity in detecting CINII and highly diseased cervical lesions and could be used as a diagnostic marker for cervical cancer of women.

scholarly journals Distribution and Prevalence of High-Risk Human Papillomavirus Genotypes in Cervical Specimens

2020 ◽  
Vol 25 (3) ◽  
pp. 325-331
Author(s):  
Erkan Özmen ◽  
Ülkü Altoparlak ◽  
Muhammet Hamidullah Uyanık ◽  
Abdulkadir Gülen
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Age Groups ◽  
Hpv Infection ◽  
High Rate ◽  
Genotype Distribution ◽  
Hpv Dna ◽  
Hpv Test ◽  
Significant Difference ◽  
Hpv Types

Introduction: Human papillomavirus (HPV) is frequently a sexually transmitted virus and can cause cervical cancer in women. Cervical cancer is the second most common type of cancer among the developing countries. In this study, cervical HPV DNA positivity and genotype distributions were investigated in female patients living in our region and the results were compared with different studies. Materials and Methods: Between 1 July, 2017 and 1 March, 2019, 433 cervical swabs were sent to Ataturk University, Medical Faculty Hospital, Medical Microbiology Laboratory due to suspicion of HPV. Swab samples were evaluated for HPV virus using molecular (Polymerase Chain Reaction-PCR) methods. For this purpose, Xpert HPV Test (Cepheid, Inc, Sunnyvale, CA) was used to identify HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 t in a single sample. Results: Mean age of the patients ranged from 20 to 69 years, with a mean of 39.8 years (± 10.0). Positivity was detected in 62 of the 433 patients. Mean age of the positive patients was 40.2 years (± 11.3). When the positive patients were examined in terms of HPV types, the presence of HPV 16 was observed with a rate of 25.6%, while the HPV 18/45 types were found to be 9.0% in total. When patients were evaluated according to age groups, HPV DNA positivity was highest in the 25-34 age group with 38.7%. In our statistical study, there was no significant difference in HPV DNA positivity rate between the ages of 35 and under 35 years. Conclusion: This study demonstrates the prevalence and viral genotype distribution of HPV infection in women in Erzurum region. HPV type 16 is seen with a high rate in our region.

Association between gene promoter methylation and cervical cancer development: global distribution and a meta-analysis

2021 ◽  
pp. cebp.0833.2020
Author(s):  
Aissam El Aliani ◽  
Hassan El Abid ◽  
Yassine El Mallali ◽  
Mohammed Attaleb ◽  
Moulay Mustapha Ennaji ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Promoter Methylation ◽  
Meta Analysis ◽  
Gene Promoter ◽  
Global Distribution ◽  
Cancer Development ◽  
Cervical Cancer Development

scholarly journals Identification of a novel circ_0018289/miR-183-5p/TMED5 regulatory network in cervical cancer development

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Heng Zou ◽  
Huijia Chen ◽  
Shuaibin Liu ◽  
Xiaoling Gan
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cell Apoptosis ◽  
Regulatory Network ◽  
Molecular Basis ◽  
Tube Formation ◽  
Cancer Development ◽  
Cervical Carcinogenesis ◽  
Cervical Cancer Development

Abstract Background Circular RNAs (circRNAs) are increasingly implicated in regulating human carcinogenesis. Previous work showed the oncogenic activity of circ_0018289 in cervical cancer. However, the molecular basis underlying the modulation of circ_0018289 in cervical carcinogenesis is still not fully understood. Methods The levels of circ_0018289, microRNA (miR)-183-5p, and transmembrane p24 trafficking protein 5 (TMED5) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Ribonuclease (RNase) R and subcellular localization assays were used to characterize circ_0018289. Cell proliferation was detected by the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (Edu) assays. Cell apoptosis and tube formation were assessed by flow cytometry and tube formation assays, respectively. A dual-luciferase reporter assay was performed to confirm the direct relationship between miR-183-5p and circ_0018289 or TMED5. The role of circ_0018289 in tumor growth was gauged by mouse xenograft experiments. Results Circ_0018289 was overexpressed in cervical cancer tissues and cells. Circ_0018289 silencing impeded cell proliferation, enhanced cell apoptosis, and suppressed angiogenesis in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0018289 targeted and regulated miR-183-5p by binding to miR-183-5p, and circ_0018289 regulated cervical cancer development and angiogenesis partially through miR-183-5p. Moreover, TMED5 was directly targeted and inhibited by miR-183-5p through the perfect complementary sites in TMED5 3′UTR, and TMED5 knockdown phenocopied miR-183-5p overexpression in suppressing cervical cancer development and angiogenesis. Furthermore, circ_0018289 induced TMED5 expression by competitively binding to shared miR-183-5p. Conclusion Our observations identified the circ_0018289/miR-183-5p/TMED5 regulatory network as a novel molecular basis underlying the modulation of cervical carcinogenesis.

Human papillomavirus (HPV) DNA and mRNA primary cervical cancer screening: Evaluation and triaging options for HPV-positive women

2019 ◽  
Vol 26 (4) ◽  
pp. 212-218
Author(s):  
Suleeporn Sangrajrang ◽  
Piyawat Laowahutanont ◽  
Metee Wongsena ◽  
Richard Muwonge ◽  
Weerawut Imsamran ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Dna Testing ◽  
Hpv Dna ◽  
Hpv Genotyping ◽  
Hpv Dna Testing ◽  
Hpv Types ◽  
Liquid Based Cytology ◽  
Hpv Mrna ◽  
Oncogenic Hpv

Objective Cervical cancer is the second most common cancer in Thai women; human papillomavirus (HPV) is the main cause. This study aimed to determine the clinical performance of HPV mRNA compared with HPV DNA testing. Methods Cervical specimens were collected from women aged 35 to 60 who attended the routine organized screening programme. We compared accuracy parameters of standalone HPV mRNA and HPV DNA tests, and those of triaging with liquid-based cytology or HPV genotyping and liquid-based cytology for those positive only for the less oncogenic HPV types. Test accuracy parameters were estimated using latent class analysis using Bayesian models. Results Of the 5046 women enrolled, 174 (3.4%) were HPV DNA positive and 141 (2.8%) HPV mRNA positive. Colposcopy compliance was 95.4% ( n = 166) among HPV DNA-positive women and 94.3% ( n = 133) among those HPV mRNA positive. The estimated sensitivity, specificity, and positive predictive value for detection of CIN2 or worse were 67.4%, 97.1%, 12.1% for HPV DNA testing, and 73.1%, 97.8%, 16.3% for HPV mRNA testing. These estimates for triaging of HPV DNA-positive women with liquid-based cytology were 64.4%, 98.8%, and 19.0%, respectively, and slightly better for liquid-based cytology triage of HPV mRNA-positive women, at 71.8%, 98.9%, and 22.1%. Conclusion A triaging strategy based on HPV genotyping and liquid-based cytology for those positive only for the less oncogenic HPV types had test characteristics comparable with that of liquid-based cytology triage. The HPV mRNA detection-based strategies had non-significant advantages over the HPV DNA detection-based strategies.

Promoter methylation of p16, DAPK, CDH1, and TIMP-3 genes in cervical cancer: correlation with clinicopathologic characteristics

2006 ◽  
Vol 16 (3) ◽  
pp. 1234-1240 ◽  
Author(s):  
D. H. Jeong ◽  
M. Y. Youm ◽  
Y. N. Kim ◽  
K. B. Lee ◽  
M. S. Sung ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Promoter Methylation ◽  
Methylation Status ◽  
Cancer Tissue ◽  
Clinicopathologic Characteristics ◽  
High Stage ◽  
Frequent Event ◽  
Clinicopathologic Parameters ◽  
Tissue Specimens ◽  
The Relationship

This study was conducted to investigate the promoter methylation status of the p16, DAPK, CDH1, and TIMP-3 genes in primary cervical cancer and its correlation with clinicopathologic characteristics. Promoter methylation was evaluated using a methylation-specific polymerase chain reaction in 78 cervical cancer tissue specimens and 24 control, normal cervical tissue specimens. Clinicopathologic parameters were obtained from medical records, and the relationship between the discrete variables and the methylation status was evaluated. The frequencies of promoter methylation of p16, DAPK, CDH1, and TIMP-3 in cervical cancer were 57%, 44.9%, 52.6%, and 9%, respectively. Primary cervical cancer had significantly higher methylation frequencies for the p16 and DAPK promoters than did the control, normal cervix (P < 0.0001). The promoter methylation of TIMP-3 was significantly higher in adenocarcinoma than in squamous cell carcinoma (41.7% vs 3%, respectively, P = 0.0175). High-stage cancers exhibited an increased promoter methylation frequency for p16 (P = 0.0061). The promoter methylation of the p16 gene is a frequent event in cervical carcinogenesis and may have potential clinical application as a marker for the progression and prognosis of cancer.

scholarly journals Gene Promoter Methylation Patterns throughout the Process of Cervical Carcinogenesis

2010 ◽  
Vol 32 (1-2) ◽  
pp. 131-143
Author(s):  
Nan Yang ◽  
Esther R. Nijhuis ◽  
Haukeline H. Volders ◽  
Jasper J. H. Eijsink ◽  
Ágnes Lendvai ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Methylation Status ◽  
Gene Promoter ◽  
Low Grade ◽  
Depth Of Invasion ◽  
Cervical Carcinogenesis ◽  
Normal Epithelium ◽  
Methylation Frequency ◽  
Cervical Cancers ◽  
Methylation Patterns

Objectives: To determine methylation status of nine genes, previously described to be frequently methylated in cervical cancer, in squamous intraepithelial lesions (SIL).Methods: QMSP was performed in normal cervix, low-grade (L)SIL, high-grade (H)SIL, adenocarcinomas and squamous cell cervical cancers, and in corresponding cervical scrapings.Results: Only CCNA1 was never methylated in normal cervices and rarely in LSILs. All other genes showed methylation in normal cervices, with CALCA, SPARC and RAR-β2 at high levels. Methylation frequency of 6 genes (DAPK, APC, TFPI2, SPARC, CCNA1 and CADM1) increased with severity of the underlying cervical lesion. DAPK showed the highest increase in methylation frequency between LSIL and HSIL (10% vs. 40%, p < 0.05), while CCNA1 and TFPI2 were most prominently methylated in cervical cancers compared to HSILs (25% vs. 52%, p < 0.05, 30% vs. 58%, p < 0.05). CADM1 methylation in cervical cancers was related to depth of invasion (p < 0.05) and lymph vascular space involvement (p < 0.01), suggesting a role in invasive potential of cervical cancers. Methylation ratios in scrapings reflected methylation status of the underlying lesions (p < 0.05).Conclusion: Methylation of previously reported cervical cancer specific genes frequently occurs in normal epithelium. However, frequency of methylation increases during cervical carcinogenesis, with CCNA1 and DAPK as the best markers to distinguish normal/LSIL from HSIL/cancer lesions.

scholarly journals Results of the first human papilloma virus center in Hungary (2007–2011)

2011 ◽  
Vol 152 (45) ◽  
pp. 1804-1807
Author(s):  
Ádám Galamb ◽  
Attila Pajor ◽  
Zoltán Langmár ◽  
Gábor Sobel
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Human Papilloma Virus ◽  
Hpv Testing ◽  
Papilloma Virus ◽  
Cytological Atypia ◽  
Hpv Dna ◽  
International Data ◽  
Hpv Types ◽  
High Risk Hpv

Human papilloma virus (HPV) is the most common sexually transmitted infection in the 21st century. It has been established that infections with specific HPV types are contributing factors to cervical cancer. Approximately 99.7% of cervical cancers are associated with high risk HPV types. HPV testing plays an important role in the prevention, by decreasing the prevalence and the mortality of cervical cancer. There are 16 HPV-centers operating in Hungary, in which patients undergo HPV screening, cervical exams, and treatment based on standardized guidelines. Patients and methods: The first HPV-center was founded in 2007 in Budapest, at the 2nd Department of Obstetrics and Gynecology, Semmelweis University. This study aimed to define the presence and prevalence of HPV-DNA in the cervical swab samples obtained from patients in our center. Authors conducted to assess the age-specific-prevalence, and HPV type distribution, the associated cervical abnormalities, comparing our results with international data. Results: Overall 1155 woman underwent HPV-testing and genotyping, using polymerase chain reaction. Overall, 55.5% of patients had positive test for HPV DNA types, in which 38.5% for high-risk HPV DNA. Overall prevalence was the highest among females aged 15 to 25years (62.9%). The most common HPV type found was the high risk type 16 (19.5% among the patients with positive HPV testing). Presence of high risk HPV with concurrent cervical cytological abnormality was in 32%. More than two-thirds of woman with cytological atypia (70.6%) were infected with two or more high risk HPV types. HPV 16 was detected in 32% of patients with cytological abnormalities. Conclusions: The results suggest that the prevalence of HPV in this study population exceeds the international data. The results attracts the attention the peak prevalence of the high risk types in the youngest age-group, and the higher risk of cervical abnormality in case of presence of two or more HPV types. The dominance of type 16 and 18 was predictable, but the strong attendance of type 51 and 31 among patients who had cytological atypia, was slightly surprising. Orv. Hetil., 2011, 152, 1804–1807.

scholarly journals Genotype-specific human papillomavirus detection in cervical smears.

2008 ◽  
Vol 55 (4) ◽  
pp. 687-692 ◽  
Author(s):  
Slawa Szostek ◽  
Malgorzata Klimek ◽  
Barbara Zawilinska ◽  
Magdalena Kosz-Vnenchak
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cervical Carcinoma ◽  
Control Group ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
Hpv Dna ◽  
Cervical Smears ◽  
Hpv Types ◽  
Intraepithelial Lesions

Human papillomavirus (HPV) is widely accepted as a causative agent of cervical cancer. The distribution and prevalence of HPV types depend on geographic region and demographic factors. The aim of this study was to investigate the relationship between the presence of various HPV types and the outcome of cytological examination. Cervical smears were obtained from 125 women from southern Poland: low grade squamous intraepithelial lesions (LSIL) - 44, high grade squamous intraepithelial lesions (HSIL) - 12, cervical carcinoma - 27 and 42 women without abnormality in cytology as a control group. DNA was extracted from the smears and broad-spectrum HPV DNA amplification and genotyping was performed with the SPF 10 primer set and reverse hybridisation line probe assay (INNO-LiPA HPV Genotyping, Innogenetics). HPV DNA was detected in approximately 72% cases, more frequently in women with squamous intraepithelial lesions and cervical carcinoma than in the control group (P < 0.0005). The most frequent type found was HPV 16 (37%), followed by HPV 51 (28%) and HPV 52 (17%). A single HPV type was detected in 51% positive cases, more frequently in cervical cancer specimens. Multiple HPV infection was dominant in women with LSIL and normal cytology. Prevalence of HPV 16 increased with the severity of cervical smear abnormality. For women HPV 16 positive, the relative risk (odds ratio) of the occurrence of HSIL and cervical cancer versus LSIL was 14.4 (95% CI, 3.0-69.2; P=0.001) and 49.4 (95% CI, 6.5-372.8; P < 0.001), respectively. Genotyping of HPV will allow better classification of women with cervical abnormalities into different risk groups and could be useful in therapy.

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