Article
Nuclear survivin expression is associated with HPV-independent carcinogenesis and is an indicator for poor prognosis in oropharyngeal cancer
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Published: | July 8, 2008 |
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Patients with human papillomavirus (HPV)-containing oropharyngeal squamous cell carcinomas (OSCC) generally have a better prognosis than patients with HPV-lacking OSCC. Survivin is an inhibitor of apoptosis and expression has been related to unfavorable prognosis in different malignancies. The relationship between survivin expression and the presence of high risk HPV in OSCC is unknown including their potential interaction for survival prediction.
Therefore, we conducted a multicenter retrospective study on 106 consecutive oropharyngeal cancer patients. HPV sequences were detected by nested PCR protocols. Survivin expression and p16 expression as a surrogate marker for HPV-status were analyzed 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 tumors. Nuclear expression of survivin was significantly correlated with HPV-negative tumors (p=0.023) and with a poor disease free survival rate with an estimated 3-year disease free survival probability of 35% for tumors with nuclear expression of survivin vs. 78% for tumors with non-nuclear expression of survivin (hazard ratio, 8.264; 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 for 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.