[1187] Role of High Risk Human Papilloma Virus (HR-HPV) in Carcinogenesis of Spindle-Cell (Sarcomatoid) Squamous Cell Carcinoma of the Head and Neck.

Oleksandr N Kryvenko, Fadi Habib, Richard J Zarbo, Frank Torres, Dhananjay A Chitale. Henry Ford Hospital, Detroit, MI

Background: Spindle-cell (sarcomatoid) squamous cell carcinoma (sSCC) of head and neck, a variant of conventional squamous cell carcinoma (cSCC) is rare but aggressive neoplasm. There have been many published reports exploring different molecular pathways in cSCC but data is limited for sSCC. In this study we explored possible role of high risk human papilloma virus infection (HR-HPV) and its association with p16, p53, Cyclin D1, MIB-1 proliferation index and EGFR expression.
Design: We identified 14 cases of sSCC from 2001-2008. The light microscopic features were reviewed and diagnosis of sSCC was rendered to tumors either entirely composed of pleomorphic spindle cells or having a distinct spindle cell component in cSCC. Tissue microarray block was constructed and following immunostains were done: p16, p53, Cyclin D1, EGFR, MIB-1. High risk HPV was detected by chromogenic in-situ hybridization (CISH) using cocktail probe (genotypes-16, 18, 33, 35, 45, 51, 52, 56, 66). Contingency table analysis of correlation between HPV status and expression of proteins was performed using Fisher's exact test. Clinical data was recorded.
Results: Nine patients (64.2%) presented with clinical stage IV, 3 (28.6%) stage I at presentation. For 2 patients clinical stage was unknown. All stage I tumors were in vocal cords, whereas stage IV disease involved larynx and Waldeyer's ring. None of the patients with stage I had disease progression after a follow-up of more than 3 years. Follow-up was available for 8 patients with stage IV cases; 5 of them succumbed to carcinoma, 2 died because of unrelated cause, and one is alive following a 2 year postoperative period. Five cases (35.7%) were p16+, 12 cases (85.7%) were HR- HPV+, p53 was mutated in 11 cases (78.6%), Cyclin D1 was upregulated in 2 cases (14.3%), and only 1 case (8%) had overexpression of EGFR. MIB-1 labeling was high in all the cases.
Conclusions: In our cohort there was an overwhelming number of sSCC which were HR-HPV+ with overexpression of p53, p16 and negative EGFR and Cyclin D1 expression. Our results indicate that aggressive behavior of sSCC is in part related to association of two carcinogenesis pathways viz. HR-HPV+ and p53 mutation unlike HR-HPV+/p53- cSCC which has more favorable clinical behavior. Interestingly, we did not find association between HR-HPV+ status and overexpression of EGFR which we found in cSCC in a separate cohort. p16 has limited value as a surrogate marker for HR-HPV status in sSCC because of low sensitivity (41.7%).
Category: Head & Neck

Tuesday, March 1, 2011 1:00 PM

Poster Session IV # 142, Tuesday Afternoon


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