title: The Value of a Novel Panel of Cervical Cancer Biomarkers for Triage of HPV Positive Patients and for Detecting Disease Progression.
abstract: In the era of primary vaccination against HPV and at the beginning of the low prevalence of cervical lesions, introduction of screening methods that can distinguish between low- and high-grade lesions is necessary in order to maintain the positive predictive value of screening. This case-control study included 562 women who attended cervical screening or were referred for colposcopy and 140 disease free controls, confirmed by histology and/or cytology. The cases were stratified by age. Using routine exfoliated liquid based cytological samples RT-PCR measurements of biomarker genes, high-risk HPV testing and liquid based cytology were performed and used to evaluate different testing protocols including sets of genes/tests with different test cut-offs for the diagnostic panels. Three new panels of cellular biomarkers for improved triage of hrHPV positive women (diagnostic panel) and for prognostic assessment of CIN lesions were proposed. The diagnostic panel (PIK3AP1, TP63 and DSG3) has the potential to distinguish cytologically normal hrHPV+ women from hrHPV+ women with CIN2+. The prognostic gene panels (KRT78, MUC5AC, BPIFB1 and CXCL13, TP63, DSG3) have the ability to differentiate hrHPV+ CIN1 and carcinoma cases. The diagnostic triage panel showed good likelihood ratios for all age groups. The panel showed age-unrelated performance and even better diagnostic value under age 30, a unique feature among the established cervical triage tests. The prognostic gene-panels demonstrated good discriminatory power and oncogenic, anti-oncogenic grouping of genes. The study highlights the potential for the gene expression panels to be used for diagnostic triage and lesion prognostics in cervical cancer screening.
authors: CellCall Ltd, Röppentyű utca 48, Budapest, 1134, Hungary.
authors: Norbert
authors: N
authors: Varga
authors: CellCall Ltd, Röppentyű utca 48, Budapest, 1134, Hungary.
authors: Johanna
authors: J
authors: Mózes
authors: Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland.|Molecular Pathology Laboratory, Department of Pathology, Coombe Women and Infants University Hospital, Dublin, 8, Ireland.
authors: Helen
authors: H
authors: Keegan
authors: Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland.|Molecular Pathology Laboratory, Department of Pathology, Coombe Women and Infants University Hospital, Dublin, 8, Ireland.
authors: Christine
authors: C
authors: White
authors: Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland.|Molecular Pathology Laboratory, Department of Pathology, Coombe Women and Infants University Hospital, Dublin, 8, Ireland.
authors: Lynne
authors: L
authors: Kelly
authors: Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland.|Molecular Pathology Laboratory, Department of Pathology, Coombe Women and Infants University Hospital, Dublin, 8, Ireland.
authors: Loretto
authors: L
authors: Pilkington
authors: CellCall Ltd, Röppentyű utca 48, Budapest, 1134, Hungary.
authors: Márta
authors: M
authors: Benczik
authors: 2nd Department of Pathology, Semmelweis University, Üllöi út 93, Budapest, 1091, Hungary.
authors: Schaff
authors: S
authors: Zsuzsanna
authors: 2nd Department of Obstetrics and Gynecology, Semmelweis University, Üllői út 78/a, Budapest, 1082, Hungary.
authors: Gábor
authors: G
authors: Sobel
authors: Department of Gynecology-Oncology, United Hospital of St. Stephan and Laszlo, Nagyvárad tér 1, Budapest, 1087, Hungary.
authors: Róbert
authors: R
authors: Koiss
authors: Department of Gynecology-Oncology, United Hospital of St. Stephan and Laszlo, Nagyvárad tér 1, Budapest, 1087, Hungary.
authors: Edit
authors: E
authors: Babarczi
authors: CellCall Ltd, Röppentyű utca 48, Budapest, 1134, Hungary.
authors: Miklos
authors: M
authors: Nyíri
authors: CellCall Ltd, Röppentyű utca 48, Budapest, 1134, Hungary.
authors: Laura
authors: L
authors: Kovács
authors: Institute of Pathophysiology, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary.
authors: Sebe
authors: S
authors: Attila
authors: Genoid Ltd, Szanatórium u. 19, Budapest, 1121, Hungary.
authors: Borbála
authors: B
authors: Kaltenecker
authors: CellCall Ltd, Röppentyű utca 48, Budapest, 1134, Hungary.
authors: Adrienn
authors: A
authors: Géresi
authors: CellCall Ltd, Röppentyű utca 48, Budapest, 1134, Hungary.
authors: Adrienn
authors: A
authors: Kocsis
authors: Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland.|Molecular Pathology Laboratory, Department of Pathology, Coombe Women and Infants University Hospital, Dublin, 8, Ireland.
authors: John
authors: J
authors: O'Leary
authors: Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland.|Molecular Pathology Laboratory, Department of Pathology, Coombe Women and Infants University Hospital, Dublin, 8, Ireland.
authors: Cara M
authors: CM
authors: Martin
authors: Department of Medical Microbiology, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary. jencsa@med.semmelweis-univ.hu.
authors: Csaba
authors: C
authors: Jeney
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003127:Colposcopy / Q000379:methods; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006367:HeLa Cells; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000473:pathology* / Q000821:virology*; D012680:Sensitivity and Specificity; D014218:Triage / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology*; D014626:Vaginal Smears / Q000379:methods; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral
keywords: Case-control study; Cellular biomarker, biomarker, cervical cancer, carcinogenesis; Cervical neoplasia; Human papillomavirus