The prognostic significance of tumor human papillomavirus status in patients with anal squamous cell carcinoma treated with combined chemoradiotherapy.

Abstract

3658 Background: The prognostic relevance of tumor human papillomavirus (HPV) status in patients (pts) with anal squamous cell carcinoma (SCC) has not been elucidated. Methods: We conducted a multicenter, retrospective, observational study and consecutively enrolled pts with newly-diagnosed invasive anal SCC treated with combined chemoradiotherapy (CCRT) from 1998 to 2009. The pts with recurrent/metastatic cancer or positive serology test for HIV were excluded. Tumor HPV status was determined by HPV DNA chip analysis from paraffin-embedded tumor tissues at initial diagnosis. Results: 47 anal SCC pts treated with CCRT and with available paraffin-embedded tissues were identified. The median age was 65.0 (range, 44-90) years, 18 (38.3%) pts had regional nodal disease (N-pos), and mitomycin-containing regimen was used in 40 (85.1%). 35 (74.5%) pts were HPV positive and 31 (66.0%) were type 16 (HPV16-pos). After median follow-up of 51.7 months (range, 5.1-136.0), the 4-year progression-free survival (PFS) and overall survival (OS) were 47.0% (95% confidence interval [CI], 38.7-55.2) and 69.2% (95% CI, 61.2-77.2). Pts with HPV16-pos had better 4-year PFS (63.1% [53.1- 73.1] vs. 15.6% [5.6-25.7], p < 0.001) and OS (84.6% [76.2-93.0] vs. 39.8% [26.1-53.4], p = 0.008) than those without HPV type 16 (HPV16-neg). In multivariate analysis for PFS, N-pos (hazard ratio [HR], 2.97; 95% CI, 1.19-7.43) and HPV16-pos (HR, 0.30; 95% CI, 0.12-0.74) were independent prognostic factors for PFS. For OS, N-pos (HR, 4.58; 95% CI, 1.40-14.98) was the only independent prognostic factor. Comparing patterns of failure, time to loco- regional failure was statistically superior in pts with HPV16-pos over those with HPV16-neg (HR, 0.24; 95% CI, 0.08-0.72, p = 0.006), but time to systemic failure was not different (HR, 0.37; 95% CI, 0.11-1.27, p = 0.098). Conclusions: In pts with anal SCC treated with CCRT, tumor HPV16 status as well as nodal status was a strong independent prognostic factor for PFS. Further studies to define the prognostic relevance of HPV16 status are warranted, and HPV16 status should be considered as an important stratification factor in future trials in anal SCC. No significant financial relationships to disclose.