The Value of a Novel Panel of Cervical Cancer Biomarkers for Triage of HPV Positive Patients and for Detecting Disease Progression

Norbert Varga, Johanna Mózes, Helen Keegan, Christine White, Lynne Kelly, Loretto Pilkington, Márta Benczik, Schaff Zsuzsanna, G. Sobel, Róbert Koiss, Edit Babarczi, Miklos Nyíri, Laura Kovács, Sebe Attila, Borbála Kaltenecker, Adrienn Géresi, Adrienn Kocsis, John O’Leary, Cara M. Martin, Csaba Jeney

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)295-305
Number of pages11
JournalPathology and Oncology Research
Volume23
Issue number2
DOIs
Publication statusPublished - Apr 1 2017

Keywords

  • Case-control study
  • Cellular biomarker, biomarker, cervical cancer, carcinogenesis
  • Cervical neoplasia
  • Human papillomavirus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oncology
  • Cancer Research

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    Varga, N., Mózes, J., Keegan, H., White, C., Kelly, L., Pilkington, L., Benczik, M., Zsuzsanna, S., Sobel, G., Koiss, R., Babarczi, E., Nyíri, M., Kovács, L., Attila, S., Kaltenecker, B., Géresi, A., Kocsis, A., O’Leary, J., Martin, C. M., & Jeney, C. (2017). The Value of a Novel Panel of Cervical Cancer Biomarkers for Triage of HPV Positive Patients and for Detecting Disease Progression. Pathology and Oncology Research, 23(2), 295-305. https://doi.org/10.1007/s12253-016-0094-1