Upregulation of telomerase (hTERT) is related to the grade of cervical intraepithelial neoplasia, but is not an independent predictor of high-risk human papillomavirus, virus persistence, or disease outcome in cervical cancer

M. Branca, C. Giorgi, M. Ciotti, D. Santini, L. Di Bonito, S. Costa, A. Benedetto, D. Bonifacio, P. Di Bonito, P. Paba, L. Accardi, L. Mariani, M. Ruutu, S. Syrjänen, C. Favalli, Kari Syrjänen, L. Leoncini, M. Alderisio, M. De Nuzzo, F. ZanconatiL. Mariani, F. Sesti, A. Criscuolo, E. Piccione, M. Galati, A. Agarossi, E. A. Casolati, M. Valieri, A. Di Carlo

Research output: Contribution to journalArticlepeer-review

Abstract

Telomerase activation and telomere maintenance are essential for cell immortalization and represent a rate-limiting step in cancer progression. The E6 oncoprotein of high-risk human papillomavirus (HPV) is known to activate telomerase, but its expression in CIN lesions and its prognostic value in cervical cancer (CC) are still incompletely understood. As part of our HPV-PathogenISS study, a series of 150 CCs and 152 CIN lesions were examined using immunohistochemical (IHC) staining for hTERT (telomerase reverse transcriptase), and tested for HPV using PCR with three primer sets (MY09/II, GP5+/GP6+, SPF). Follow-up data were available from all SCC patients, and 67 CIN lesions had been monitored with serial PCR for HPV after cone treatment. Expression of hTERT was increased in parallel with the grade of CIN, with major up-regulation upon transition to CIN3 (OR 18.81; 95% CI 8.48-41.69; P = 0.0001). Positive hTERT expression was 90% specific indicator of CIN, with 98.7% PPV, but suffers from low sensitivity (57.5%) and NPV (14.3%), hTERT expression was also significantly associated to HR-HPV with OR 3.38 (95% CI 1.90-6.02: P = 0.0001), but this association was confounded by the histological grade (Mantel-Haenszel common OR = 1.83: 95% CI 0.92-3.79: P = 0.086). Expression of hTERT did not predict clearance/persistence of HR-HPV after treatment of CIN, and it was not a prognostic predictor in cervical cancer in univariate or multivariate survival analysis. It was concluded that up-regulation of hTERT was closely associated with HR-HPV, due to activation by the E6 oncoprotein. hTERT is a late marker of cervical carcinogenesis, significantly associated with progression to CIN3. Theoretically, a combination of hTERT assay (showing high SP and PPV) with another test showing high SE and high NPV (e.g. Hybrid Capture 2 for HPV), should provide an ideal screening tool capable of high-performance detection of CIN lesions.

Original languageEnglish
Pages (from-to)739-748
Number of pages10
JournalDiagnostic Cytopathology
Volume34
Issue number11
DOIs
Publication statusPublished - Nov 2006

Keywords

  • Cervical cancer
  • hTERT
  • Oncogenic human papillomavirus
  • Persistence
  • Prognosis
  • Telomerase
  • Treatment
  • Virus clearance

ASJC Scopus subject areas

  • Anatomy

Fingerprint Dive into the research topics of 'Upregulation of telomerase (hTERT) is related to the grade of cervical intraepithelial neoplasia, but is not an independent predictor of high-risk human papillomavirus, virus persistence, or disease outcome in cervical cancer'. Together they form a unique fingerprint.

Cite this