A33: Vulvar squamous cell carcinomas: HPV status defines outcomes
1University of British Columbia, Vancouver, Canada
The last decades have seen an increasingly conservative approach to management of vulvar squamous cell carcinoma (VSCC). Although surgical morbidity has decreased there are concerns that overall outcomes are worse. VSCC develops through HPV-associated or HPV-independent mechanisms yet at present these women are treated identically. We wished to determine whether HPV status is associated with outcomes in a large cohort of patients with VSCC.
We identified women with VSCC operated on between 1985-2005. Clinicopathologic parameters, treatments, and outcomes were recorded. HPV status of tumors was assessed by multiple modalities, including p16 immunohistochemistry (IHC).
Over 400 cases were identified. Pathologic review, archival material, and complete clinical data were available in 218. HPV testing by three methods of DNA detection and p16 immunostaining was performed in a subset of cases. p16 IHC proved to be a suitable surrogate for molecular testing and was performed on the remainder of the cohort:122 HPV-negative (61%) and 79 HPV-positive (39%) tumors. Median age of each group was 75 and 58 years respectively (p<.001).Tumor size, stage distribution, and adjuvant treatments were similar in both groups, however, lymphovascular space invasion and node positivity was more common in HPV-independent tumors. Outcomes differed significantly in the HPV negative versus positive cohorts: median overall survival (OS) 3.06 vs. 5.96 years, disease-specific survival (DSS) 3.13 vs. 5.66 years, relapse-free survival (RFS) 0.73 vs. 3.89 years. Factors associated with outcomes in univariable analysis included HPV status, age, tumor size, any positive node, and adjuvant treatment; HPV status showed the strongest association with outcomes on multivariable analysis. Kaplan Meier analyses demonstrated significant differences curves for OS, DSS and RFS (log-rank p=0.0004, <0.000001, and 0.023 respectively), based on HPV status.
Development of treatment algorithms specific to HPV-associated versus HPV-independent vulvar carcinomas are needed, as have been successfully implemented in oropharyngeal carcinomas.