Prognostic significance of high-risk human papilloma virus (HPV), p16, and p53 status in women with vulvar squamous cell carcinoma (VSCC).

Abstract

5105 Background: The incidence of VSCC is increasing. Studies suggest the presence of two histologically and molecularly distinct subsets of VSCC; one contingent on and another independent of HPV infection. However, it is uncertain if HPV status has prognostic significance. HPV oncoproteins can result in degradation of the tumor suppressor p53, cell cycle deregulation and abnormal expression of cyclin dependant kinase inhibitor p16. The aim of this study was to investigate HPV infection, p16 and p53 in relation to clinical parameters in women with VSCC. Methods: Sequential cases of VSCC from patients (pts) treated at Princess Margaret Hospital (PMH) from 2000 to 2008 were reviewed. HPV infection was evaluated by Roche Linear array. A tissue microarray was constructed. p16 and p53 immunohistochemistry was performed. Clinical data was abstracted from medical records and PMH Cancer Database. Survival analysis was performed using Kaplan-Meier curves and log rank test. Results: We identified124 pts with VSCC. HPV was detected in 43/123 (35%) pts (median age 71 ± 16 yrs). HPV16 was the most common serotype (38/43; 88.4%). p16 was expressed in 30/115 (26%) pts and p53 in 59/117 (50.4%) pts. Median age of pts was not different in relation to HPV, p16 and p53 status. Expression of p16 (p<0.0001) and loss of p53 (p=0.007) were associated with HPV infection. Pts with HPV positive tumors were less likely to recur (recurrence rate at 5 years (RR) 12.5% vs 50.3%, p=0.009). HPV positive VSCC were not associated with better 5 yr disease free survival (DFS), 58% vs 31%; p=0.15, or overall survival (OS), 61% vs 61% ; p=0.94. p16 positive tumors had a lower RR at 5 yrs, 23.8% vs 59%, p=0.006 and better 5yr DFS (61% vs 27% ; p=0.009) but not significant for OS (65% vs 59%; p=0.94). Among pts with HPV positive VSCC, OS and DFS were not different between p16 positive and negative VSCC. In the 46 pts treated with radiotherapy, HPV and p16 positive tumors were associated with a lower RR (p=0.004 and 0.005). p53 expression was not prognostic in any pt group. Conclusions: Women with HPV-positiveVSCC have a lower risk of disease recurrence. p16-expressing VSCC are associated with reduced disease recurrence and improved DFS.