Viral and Cellular Biomarkers in the Diagnosis of Cervical Intraepithelial Neoplasia and Cancer

Tornesello, Maria Lina; Buonaguro, Luigi; Rossi, Paolo Giorgi; Buonaguro, Franco M.

doi:10.1155/2013/519619

Cited by 108 publications

(99 citation statements)

References 72 publications

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“…That marker might be used to reduce the number of women referred to a more careful monitoring and follow-up regime, raising the specificity of assessment in women with atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesions (LSILs) (Varnai et al, 2008;Keegan et al, 2009;Brown and Trimble, 2012;Tornesello et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Expression of human papillomavirus E6 and E7 oncoprotein mRNA in women with low-grade squamous intraepithelial lesions or less

et al. 2016

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ABSTRACT. We verified the prevalence of human papillomavirus (HPV) E6/E7 protein mRNA expression in patients with low-grade squamous intraepithelial lesions (LSILs) and negative cervicovaginal cytology. To investigate the relationship between mRNA expression and viral infection type, we assessed genotyping in single infections. Samples from 825 women were submitted to the E6/E7 survey. We noticed a larger percentage of E6/E7 mRNA expression in the atypical squamous cells of undetermined significance (ASC-US) and LSIL cytologies. Negative results of mRNA expression were in accordance with negative cytologies. In positive cases, the infection by a single HPV type was most common, with type 16 being most prevalent. The expression of mRNA was most prevalent in ASC-US and LSIL cytologies, compared with the negative cytology. The infection by a HPV type was more frequent in cases of positive expression, with HPV

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Section: Introductionmentioning

confidence: 99%

Expression of human papillomavirus E6 and E7 oncoprotein mRNA in women with low-grade squamous intraepithelial lesions or less

et al. 2016

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“…Increased expression of TOP2A was identified in cervical cancer using different high-throughput expression profiling technologies (22). The TOP2A and MCM2 genes have been identified as molecular markers for the diagnosis of cervical cancer (23,24). Similar studies have also demonstrated that TOP2A was upregulated in cervical cells and tissues with elevated expression of the HPV E6/E7 proteins (25,26).…”

Section: Discussionmentioning

confidence: 99%

Investigation of differentially-expressed microRNAs and genes in cervical cancer using an integrated bioinformatics analysis

Zhou

Shi

et al. 2017

Oncology Letters

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Abstract. Cervical cancer is one of the most common types of cancer among women worldwide. In order to identify the microRNAs (miRNAs/miRs) and mRNAs associated with the carcinogenesis of cervical cancer, and to investigate the molecular mechanisms of cervical cancer, an miRNA microarray, GSE30656, and 3 mRNA microarrays, GSE63514, GSE39001 and GSE9750, for cervical cancer were retrieved from Gene Expression Omnibus. These datasets were analyzed in order to obtain differentially-expressed genes (DEGs) and miRNAs using the GEO2R tool. Gene Ontology (GO) and pathway enrichment analysis for DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction (PPI) analysis for DEGs was conducted using The Search Tool for the Retrieval of Interacting Genes software and visualized using Cytoscape, followed by hub gene identification, and biological process and pathway enrichment analysis of the module selected from the PPI network using the Molecular Complex Detection plugin. In addition, miRecords was applied to predict the targets of differentially-expressed miRNAs. A total of 44 DEGs and 15 differentially-expressed miRNAs were identified. These DEGs were mainly enriched in GO terms associated with the cell cycle. In the PPI network, cyclin-dependent kinase 1, topoisomerase DNA IIα, aurora kinase A (AURKA) and minichromosome maintenance complex component 2 (MCM2) had higher degrees of connectivity. A significant module was detected from the PPI network. AURKA, MCM2 and kinesin family member 20A exhibited higher degrees in this module, while the genes in the module were mainly involved in the cell cycle and the DNA replication pathway. In addition, estrogen receptor 1 was predicted as the potential target of 13 miRNAs. A total of 10 DEGs were identified as potential targets of miR-203. In conclusion, the results indicated that microarray dataset analysis may provide a useful method for the identification of key genes and patterns to successfully identify determinants of the carcinogenesis of cervical cancer. The functional studies of candidate genes and miRNAs from these databases may lead to an increased understanding of the development of cervical cancer.

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“…Overexpression of p16 and Ki-67 have proven to be useful indicators of clinically significant infections and lesion severity in numerous studies (11,18,19); several properties of p16 and Ki-67 enable them to be promising biomarkers for HPV-associated cancer, since they are associated with histological grade and infection for HR-HPV (17). In addition, p16 immunostaining appears to be a useful adjunctive test in the examination of colposcopically-directed cervical biopsies and in the diagnostic cascade of women investigated for abnormal Papanicolaou smears, due to its capacity to reveal the integration of high-risk HPV DNA into the host cell genome (20).…”

Section: Discussionmentioning

confidence: 99%

“…Ki-67 is a non-histone protein that exists as two isoforms encoded by cDNA sequences of 11.5 and 12.5 kb organized over 15 exons and localized on chromosome 10 (9). Its expression is applied to assess the growth fraction of a cell population (10 (11,12). Based on the aforementioned data, the present study evaluated Ki-67 and p16 immunostaining in CIN lesions diagnosed in pregnancy compared with those diagnosed in non-pregnant women.…”

Section: Introductionmentioning

confidence: 99%

Cervical intraepithelial neoplasia in pregnancy: Interference of pregnancy status with p16 and Ki-67 protein expression

et al. 2016

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Abstract. To date, there are evidence-based guidelines available for cervical dysplasia diagnosed in pregnancy. Certain functional biomarkers have proven useful in the prediction of regressing and non-regressing cervical intraepithelial neoplasia (CIN) lesions in non-pregnant women. In the present study, Ki-67 and p16 immunostaining were evaluated in different grades of CIN lesions diagnosed in pregnant or non-pregnant women with the aim to identify any differences in order to better understand the behavior of CIN in pregnancy. The current retrospective case-control study included 17 pregnant patients that conceived naturally with first-time onset of CIN occurring at no later than 16 gestational weeks. The control group included 17 non-pregnant patients matched for age, parity and number of previous sexual partners. Exclusion criteria included previous cervical treatment, immunocompromised status, chronic hepatitis B and/or C and cigarette smoking. p16 and Ki-67 protein expression were respectively detected using the CINtec Histology kit and monoclonal antibodies against Ki-67. p16 and Ki-67 staining were analyzed using a classification system based on the distribution of positivity on a semi-quantitative three point-scale. p16 and Ki-67 immune reactivity correlated positively with the grade of epithelial dysplasia in the total cohort of pregnant and non-pregnant patients; expression increased linearly from CIN1 to CIN3. Furthermore, the association between p16 immunostaining and CIN grade was significant in non-pregnant patients but not in pregnant patients. In pregnant patients, positivity for Ki-67 was less intense than in non-pregnant patients. These results appear to suggest that pregnancy status interferes with the expression of cellular proteins involved in cell-cycle regulation and the carcinogenic process induced by high-risk human papilloma virus, exhibiting increased variability in their staining. IntroductionThe results of Pap tests performed during routine screenings at the beginning of prenatal care are abnormal in 8-12% of cases (1). Overall, the prevalence of abnormal cervical cytology in pregnancy is similar to that of age-matched, non-pregnant women (2). The incidence of cervical intraepithelial neoplasia (CIN) in pregnancy varies among different patient populations, as it does in non-pregnant women, but when age-matched, the risk of CIN is not higher than that among women who are not pregnant, ranging between 3.4 and 10.0% (3). The management of pregnant women with abnormal cytology depends on the degree of cytological abnormality, the outcome of colposcopy, and, when necessary, directed biopsy. Since, the only diagnosis that may alter management in pregnancy is invasive cancer, the management of pregnant women with abnormal cervical cytology or biopsy-proven CIN is generally more conservative compared with management of similar cytology and histology in non-pregnant women. However, management guidelines for cervical dysplasia are not well defined and are based on data collected from non-pregn...

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Viral and Cellular Biomarkers in the Diagnosis of Cervical Intraepithelial Neoplasia and Cancer

Cited by 108 publications

References 72 publications

Expression of human papillomavirus E6 and E7 oncoprotein mRNA in women with low-grade squamous intraepithelial lesions or less

Expression of human papillomavirus E6 and E7 oncoprotein mRNA in women with low-grade squamous intraepithelial lesions or less

Investigation of differentially-expressed microRNAs and genes in cervical cancer using an integrated bioinformatics analysis

Cervical intraepithelial neoplasia in pregnancy: Interference of pregnancy status with p16 and Ki-67 protein expression

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