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

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 p16^INK4a 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.

Author notes

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HPV-Pathogen ISS Study Group: Fabio Sesti, MD,¹ Marco Galati, MD,^2,3 Anna Angelia Criscuolo, PhD,¹ Alberto Agarossi, MD,⁴ Monica Valieri, MD,⁴ Emilio Piccione, MD,¹ Maria De Nuzzo, MD,⁵ Aldo di Carlo, MD, PhD,³ Luciano Leoncini,⁶ and Mauro Alderisio, MD,⁶ from the ¹Istituto di Ginecologia, Università di Tor Vergata, Rome, Italy; ²Ginecologia e Ostetrica, IFO, Istituto Regina Elena, Rome; ³IFO, Istituto San Gallicano, Unità Operativa MST/HIV, Rome; ⁴Clinica Ostetrica e Ginecologia, Istituto Scienze Biomediche, Ospedale Luigi Sacco, Milan, Italy; ⁵Dipertimento di Ginecologia e Ostetrica, Azienda Ospedaliera S. Orsola Malpighi, Bologna, Italy; ⁶Unità Citoistopatologia, Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, Istituto ISS, Rome.

Supported by a grant from the Italian Ministry of Health, Rome (2002; Fasc. OG/C).