PAX1 methylation as an auxiliary biomarker for cervical cancer screening: A meta-analysis

Nikolaidis, Christos; Nena, Evangelia; Παναγοπούλου, Μαρία; Balgkouranidou, Ioanna; Karaglani, Makrina; Chatzaki, Εkaterini; Αγοραστός, Θεόδωρος; Constantinidis, Theodoros C.

doi:10.1016/j.canep.2015.07.008

Cited by 25 publications

(19 citation statements)

References 38 publications

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“…The second tested biomarker, PAX1 m , has also been reported as a useful biomarker for cervical cancer in the screening and triage of cytology and for the detection cervical adenocarcinoma. The results of this meta-analysis support the utility of PAX1 m as an auxiliary biomarker in cervical cancer screening [ 33 ], as algorithm 1 demonstrated 89.87 % sensitivity and 75.95 % specificity for PAX1 m in combination with HPV16/18 and cytology testing, which is higher than the values obtained by testing any of these factors alone.…”

Section: Case Presentationsupporting

confidence: 60%

Combined clinical and genetic testing algorithm for cervical cancer diagnosis

et al. 2016

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BackgroundOpportunistic screening in hospitals is widely used to effectively reduce the incidence rate of cervical cancer in China and other developing countries. This study aimed to identify clinical risk factor algorithms that combine gynecologic examination and molecular testing (paired box gene 1 (PAX1) or zinc finger protein 582 (ZNF582) methylation or HPV16/18) results to improve diagnostic accuracy.MethodsThe delta Cp of methylated PAX1 and ZNF582 was obtained via quantitative methylation-specific PCR in a training set (57 CIN2− and 43 cervical intraepithelial neoplasia ≥grade 3 (CIN3+) women), and the individual and combination gene sensitivities and specificities were determined. The detection accuracy of three algorithms combining gynecologic findings and genetic test results was then compared in a randomized case-control study comprising 449 women referred for colposcopic examination by gynecologists in the outpatient department of Xiangya Hospital between November 2011 and March 2013.ResultsSignificant association was observed between CIN3+ and methylated PAX1 or ZNF582 in combination with HPV16/18 (OR:15.52, 95 % CI:7.73–31.18). The sensitivities and specificities of methylated PAX1 or ZNF582 combined with HPV16/18 for CIN3+ women were 89.2 and 76.0 %, or 85.4 and 80.1 %, respectively. Of the three algorithms applied to cohort data and validated in the study, two indicated 100 % sensitivity in detecting cervical cancer and a low rate of referrals for colposcopy.ConclusionsThese algorithms might contribute to precise and objective cervical cancer diagnostics in the outpatient departments of hospitals in countries with high mortality and low screening rates or areas with uneven resource distribution.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0232-3) contains supplementary material, which is available to authorized users.

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Section: Case Presentationsupporting

confidence: 60%

Combined clinical and genetic testing algorithm for cervical cancer diagnosis

et al. 2016

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“…Mersakova et al (2018) and Rong et al (2019) have recently shown that CADM1 is a potential biomarker for cervical cancer. There was a significant difference in the promoter Kan et al, 2014;Lai et al, 2014;Kong et al, 2015;Nikolaidis et al, 2015;Xu et al, 2015Xu et al, , 2018Chen et al, 2016;Liou et al, 2016;Huang et al, 2017;Fang et al, Lee et al, 2006;Yeon et al, 2018 methylation of plasma CADM1 and its D-dimer between healthy individuals and those with cervical cancer. Combining these factors to predict metastasis revealed high specificity (90.5%) and sensitivity (80.4%) (Rong et al, 2019).…”

Section: Dna Methylation In the Early Diagnosis Of Cervical Cancermentioning

confidence: 97%

“…A meta-analysis comprising Asian individuals revealed that the sensitivity and specificity of PAX1 methylation is 73 and 87%, respectively in HSIL/CIN3 + /cervical cancer patients (Chen et al, 2016). Another meta-analysis used 1,385 individuals with different stages of CIN to show that the sensitivity and specificity of PAX1 methylation in CIN3 + samples are 77% and 92%, respectively (Nikolaidis et al, 2015). In summary, different geographical locations and various methods (especially using combinations) affect the sensitivity and specificity of detecting PAX1 methylation.…”

Section: Diagnostic Dna Methylation Biomarkers For Hpv-positive and Nmentioning

confidence: 99%

DNA Methylation and Hydroxymethylation in Cervical Cancer: Diagnosis, Prognosis and Treatment

Zhu

Tian

et al. 2020

Front. Genet.

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Recent discoveries have led to the development of novel ideas and techniques that have helped elucidate the correlation between epigenetics and tumor biology. Nowadays, the field of tumor genetics has evolved to include a new type of regulation by epigenetics. An increasing number of studies have demonstrated the importance of DNA methylation and hydroxymethylation in specific genes in the progression of cervical cancer. Determining the methylation and hydroxymethylation profiles of these genes will help in the early prevention and diagnosis, monitoring recurrence, prognosis, and treatment of patients with cervical cancer. In this review, we focus on the significance of aberrant DNA methylation and hydroxymethylation in cervical cancer and the use of these epigenetic signatures in clinical settings.

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“…In addition, combining analysis of host gene methylation with hrHPV DNA testing appears to be a new strategy in cervical cancer screening. Better specificity for host gene methylation status could improve the accuracy of detection of advanced cervical abnormalities in HPV-positive women [14]. ZNF582 and a methylation panel tested in parallel with testing for hrHPV DNA has a greater accuracy for detection of CIN2 and more severe lesions than gene methylation alone [1516].…”

Section: Introductionmentioning

confidence: 99%

Genotype-specific methylation of HPV in cervical intraepithelial neoplasia

Hsu

Huang

et al. 2017

J Gynecol Oncol

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ObjectiveHypermethylation of human papillomavirus (HPV) and host genes has been reported in cervical cancer. However, the degree of methylation of different HPV types relative to the severity of the cervical lesions remains controversial. Studies of the degree of methylation associated with the host gene and the HPV genome to the severity of cervical lesions are rare. We examined the association of methylation status between host genes and late gene 1 (L1) regions of HPV16, 18, 52, and 58 in cervical brushings.MethodsCervical brushings from 147 HPV-infected patients were obtained. The samples comprised normal (n=28), cervical intraepithelial neoplasia (CIN) 1 (n=45), CIN2 (n=13), and CIN3/carcinoma in situ (n=61). The methylation status of HPV and host genes was measured using bisulfite pyrosequencing and quantitative methylation-specific polymerase chain reaction (PCR).ResultsThe degree of methylation of L1 in HPV16, 18, and 52 was associated with the severity of the cervical lesion. In HPV52, C-phosphate-G (CpG) sites 6368m, 6405m, and 6443m showed significantly higher methylation in lesions ≥CIN3 (p=0.005, 0.003, and 0.026, respectively). Methylation of most HPV types except HPV52 (r<−0.1) was positively correlated with the degree of methylation of host genes including PAX1 and SOX1 (0.4≤r≤0.7). Combining HPV methylation with PAX1 methylation improved the clustering for ≥CIN2.ConclusionOur study showed that the degree of L1 methylation of HPV16, 18, and 52 but not 58 is associated with the severity of cervical lesions. The association between HPV methylation and host gene methylation suggests different responses of host cellular epigenetic machinery to different HPV genotypes.

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PAX1 methylation as an auxiliary biomarker for cervical cancer screening: A meta-analysis

Cited by 25 publications

References 38 publications

Combined clinical and genetic testing algorithm for cervical cancer diagnosis

Combined clinical and genetic testing algorithm for cervical cancer diagnosis

DNA Methylation and Hydroxymethylation in Cervical Cancer: Diagnosis, Prognosis and Treatment

Genotype-specific methylation of HPV in cervical intraepithelial neoplasia

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