Human Papillomavirus Genotyping and p16 Expression As Prognostic Factors for Patients With American Joint Committee on Cancer Stages I to III Carcinoma of the Anal Canal

Abstract

PURPOSE: Carcinomas of the anal canal are strongly associated with the human papillomavirus (HPV). Expression of p16 is used as a surrogate marker of HPV infection. In a retrospective study, we evaluated HPV genotyping and p16 expression as prognostic markers of overall survival (OS) and disease-specific survival (DSS) in patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to III carcinoma of the anal canal. PATIENTS AND METHODS: HPV genotyping polymerase chain reaction (high-risk subtypes 16, 18, 31, 33, 45, 52, and 58) and immunohistochemical expression of p16 were analyzed by using paraffin-embedded tumor biopsies from 143 anal carcinomas. The patients were treated with combined chemoradiotherapy or radiotherapy alone. RESULTS: HPV16 was detected in 81.0% of the tumors, followed by HPV33 (5.1%), HPV18 (2.2%), and HPV58 (0.7%). p16 positivity was found in 92.9% of the tumors. In univariable survival analysis, HPV positivity was significantly correlated with improved OS (74% v 52%; P=.036) and DSS (84% v 52%; P=.002), and p16 positivity was significantly correlated with improved OS (76% v 30%; P<.001) and DSS (85% v 30%; P<.001). In multivariable COX analysis that included HPV status, p16 status, sex, T stage, N stage, and treatment, p16 positivity remained an independent prognostic factor for OS (hazard ratio [HR], 0.07; 95% CI, 0.01 to 0.61; P=.016) and DSS (HR, 0.07; 95% CI, 0.01 to 0.53; P=.011). CONCLUSION: p16 positivity is an independent prognostic factor for OS and DSS in patients with AJCC stages I to III carcinoma of the anal canal.