Combined analysis of HPV DNA, p16, p21 and p53 to predict prognosis in patients with stage IV hypopharyngeal carcinoma

We examined p16, p21 and p53 expression in combination with the presence of human papillomavirus (HPV) DNA as molecular markers to predict survival in patients with stage IV hypopharyngeal squamous cell carcinoma (HSCC). Paraffin-embedded tumours from HSCC patients (n = 75) were evaluated for p16, p21 and p53 expression by immunohistochemistry. HPV DNA was detected by GP5+/6+ consensus PCR and subsequent genotyping by E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. Among the 61 specimens that tested positive for the beta-globin, HPV typing identified 50 patients with high-risk (hr) HPV types. HPV 16E7 DNA was detected in 74% (37 cases) of these specimens. Twelve patients were found to be infected with multiple HPV types. However, the presence of hrHPV DNA was not found to correlate with the proportion of disease-free patients. The 5-year disease-free survival rate was 73% in p53- tumours versus 48% in p53+ tumours (P = 0.008). In our series of patients with stage IV HSCC, the hrHPV+ subgroup had a similar prognosis (in terms of recurrence risk) as the HPV- subgroup. p53 overexpression was associated with a worse prognosis.