title: PAX1 methylation as an auxiliary biomarker for cervical cancer screening: a meta-analysis.
abstract: OBJECTIVE
  Several studies have implicated PAX1 epigenetic regulation in cervical neoplasia. The aim of this meta-analysis was to assess PAX1 gene methylation as a potential biomarker in cervical cancer screening.
  
  
  METHODS
  A systematical search of all major databases was performed, in order to include all relevant publications in English until December 31(st) 2014. Studies with insufficient data, conducted in experimental models or associated with other comorbidities were excluded from the meta-analysis. Summary receiver operating characteristics (SROC) for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2(+)) versus normal, and CIN grade 3 or worse (CIN3(+)) versus normal, were estimated using the bivariate model.
  
  
  RESULTS
  Out of the 20 initially included studies, finally 7 (comprising of 1385 subjects with various stages of CIN and normal cervical pathology) met the inclusion criteria. The sensitivity of CIN2(+) versus normal was estimated to be 0.66 (CI 95%, 0.46-0.81) and the specificity 0.92 (CI 95%, 0.88-0.95). On the other hand, the sensitivity of CIN3(+) versus normal was 0.77 (CI 95%, 0.58-0.89) and the specificity 0.92 (CI 95%, 0.88-0.94). Moreover, the area under the curve (AUC) in the former case was 0.923, and in the latter 0.931.
  
  
  CONCLUSIONS
  The results of this meta-analysis support the utility of PAX1 methylation as an auxiliary biomarker in cervical cancer screening. PAX1 could be used effectively to increase the specificity of HPV DNA by detecting women with more advanced cervical abnormalities.
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece. Electronic address: cnikolae@med.duth.gr.
authors.forename: Christos
authors.initials: C
authors.lastname: Nikolaidis
authors.affiliation: Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Nena
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Panagopoulou
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Balgkouranidou
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors.forename: Makrina
authors.initials: M
authors.lastname: Karaglani
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Chatzaki
authors.affiliation: IV. University Clinic of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, Hippokrateion Hospital, Thessaloniki 54642, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Agorastos
authors.affiliation: Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
authors.forename: Theodoros C
authors.initials: TC
authors.lastname: Constantinidis
mesh_terms: D000328:Adult; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D051761:Paired Box Transcription Factors / Q000235:genetics*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D051761:Paired Box Transcription Factors; C070835:PAX1 transcription factor
keywords: Cervical cancer; Meta-analysis; Methylation; PAX1