title: Nuclear survivin expression is associated with HPV-independent carcinogenesis and is an indicator of poor prognosis in oropharyngeal cancer.
abstract: The relationship between expression of the inhibitor of apoptosis protein survivin and the presence of high-risk human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC) remains unclear. This also accounts for its role as a predictor of survival. Therefore, we conducted a multicentre retrospective study on 106 consecutive oropharyngeal cancer patients. Human papillomavirus sequences were detected by nested PCR protocols. Survivin and p16 expression as a surrogate marker for HPV status were analysed by immunohistochemistry. Sequences of high-risk HPV were detected in 29% of cases. Prominent cytoplasmatic expression of survivin was found in 58% of cases and nuclear expression of survivin was found in 19% of the survivin-positive tumours. Nuclear expression of survivin was significantly correlated with HPV-negative tumours (P=0.023) and with a poor disease-free survival rate with an estimated 3-year disease-free survival probability of 35% for tumours with nuclear expression of survivin vs 78% for tumours with non-nuclear expression of survivin (hazard ratio=8.264; 95% confidence interval (95% CI)=2.510-27.210; P<0.001). In multivariate analysis, p16 expression status as well as nuclear expression of survivin were strong independent and opposing prognostic indicators of disease-free survival (hazard ratio=0.068; 95% CI=0.005-0.892; P=0.041 and hazard ratio=15.975; 95% CI=2.377-107.360; P=0.004, respectively). Our data show that nuclear accumulation of survivin correlates with HPV-independent carcinogenesis and is an independent predictor of poor survival in patients with OSCC.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, University Hospital of Cologne, Cologne, Germany. simon.preuss@uni-koeln.de
authors.forename: S F
authors.initials: SF
authors.lastname: Preuss
authors.forename: A
authors.initials: A
authors.lastname: Weinell
authors.forename: M
authors.initials: M
authors.lastname: Molitor
authors.forename: M
authors.initials: M
authors.lastname: Stenner
authors.forename: R
authors.initials: R
authors.lastname: Semrau
authors.forename: U
authors.initials: U
authors.lastname: Drebber
authors.forename: S J
authors.initials: SJ
authors.lastname: Weissenborn
authors.forename: E J M
authors.initials: EJ
authors.lastname: Speel
authors.forename: C
authors.initials: C
authors.lastname: Wittekindt
authors.forename: O
authors.initials: O
authors.lastname: Guntinas-Lichius
authors.forename: T K
authors.initials: TK
authors.lastname: Hoffmann
authors.forename: G D
authors.initials: GD
authors.lastname: Eslick
authors.forename: J P
authors.initials: JP
authors.lastname: Klussmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000821:virology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009959:Oropharyngeal Neoplasms / Q000378:metabolism* / Q000821:virology; D011379:Prognosis; D012189:Retrospective Studies; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin