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Survivin as a Marker of Cervical Intraepithelial Neoplasia and High-Risk Human Papillomavirus and a Predictor of Virus Clearance and Prognosis in Cervical Cancer

Margherita Branca MD, PhD, MIAC, Colomba Giorgi PhD, Donatella Santini MD, Luigi Di Bonito MD, Marco Ciotti MD, Silvano Costa MD, Arrigo Benedetto MD, Elena A. Casolati MD, Cartesio Favalli MD, Pierluigi Paba MD, Paola Di Bonito MD, Luciano Mariani MD, Stina Syrjänen DDS, PhD, Donatella Bonifacio MD, Luisa Accardi MD, Francesca Zanconati MD, Kari Syrjänen MD, PhD, FIAC,
DOI: http://dx.doi.org/10.1309/L8BWF431WU9AC8FJ 113-121 First published online: 1 July 2005

Abstract

We analyzed survivin as a marker of cervical intraepithelial neoplasia (CIN) and high-risk human papillomavirus (HR-HPV) and a predictor of HPV clearance and disease outcome in cervical cancer in 302 samples (squamous cell carcinomas [SCCs], 150; CIN lesions, 152) by immunohistochemical staining with survivin antibody and HPV testing using polymerase chain reaction.

HR-HPV types were associated closely with CIN and SCC. There was a significant linear relationship between grade and intensity of survivin expression (P = .0001). Survivin overexpression also was associated strongly with HR-HPV type (P = .0001). Multivariate regression analysis revealed survivin and p16INK4a as equally strong independent predictors of HR-HPV. Deregulated survivin expression did not predict clearance or persistence of HR-HPV after treatment of CIN or survival in cervical cancer in univariate (P = .417) or multivariate analysis. After adjustment for HR-HPV, stage, age, and tumor grade in the Cox regression model, only stage (P = .0001) and age (P = .0001) remained independent prognostic predictors.

Survivin seems to be an early marker of cervical carcinogenesis. Up-regulated survivin expression was an independent predictor of HR-HPV in cervical lesions, most plausibly explained by its normal transcriptional repression by wild-type p53 being eliminated by HR-HPV E6 oncoprotein.

Key Words:
  • Survivin
  • Apoptosis inhibitor
  • Human papillomavirus
  • Cervical intraepithelial neoplasia
  • CIN
  • Cervical cancer
  • Prognosis
  • Virus clearance
  • High-risk HPV