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 ¼ 0.023) and with a poor diseasefree 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 ¼ 8.264; 95% confidence interval (95% CI) ¼ 2.510 -27.210; Po0.001). 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 ¼ 0.068; 95% CI ¼ 0.005 -0.892; P ¼ 0.041 and hazard ratio ¼ 15.975; 95% CI ¼ 2.377 -107.360; P ¼ 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.

Human Papillomavirus-Related Head and Neck Cancer

“…It suppresses apoptosis and plays a role in cell division. Nuclear survivin expression was correlated with a poor disease-free survival rate and negative HPV status in OPSCC [21].…”

Prognostic impact of human papillomavirus status, survivin, and epidermal growth factor receptor expression on survival in patients treated with radiochemotherapy for very advanced nonresectable oropharyngeal cancer

“…5,14 Primary antibodies were detected using the avidin-biotinylated peroxidase complex (ABC) procedure (Chem Mate Detection kit; Dako Cytomation, Carpinteria, CA). Peroxidase activity was visualized using 3-Amino-9-Ethylcarbazol (AEC, Dako Cytomation) and sections were counterstained with hematoxylin.…”

“…In particular, the nuclear expression of the inhibitor of apoptosis protein survivin is reported to be associated with a poor survival. 5 Whereas well-established risk factors for head and neck squamous cell carcinomas (HNSCCs) are smoking and alcohol consumption, the role of oncogenic HPV in the development of oropharyngeal SCC became evident over the past years. HPV associated HNSCCs are most frequently located in the tonsillar region and the base of tongue and about 35% of all oropharyngeal SCCs are considered to be HPV associated.…”

The impact of Survivin, WRAP53β, and Hypoxia on treatment response in Head and Neck Cancer

“…Strong survivin expression was significantly associated with improved radiotherapy response and longer overall survival. These results were in contrast to other studies that reported a poor prognosis in tumors overexpressing survivin (64,107). In those studies, the expression of survivin was determined by the percentage of positively stained cells only, without consideration of the staining intensity.…”