Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations.

Abstract

The role of human papilloma virus (HPV) in the pathogenesis and biological behavior of tonsillar squamous cell carcinoma (TSCC) are areas of intense investigation. This study used PCR analysis to identify HPV in paraffin-embedded tonsillar and nodal tissue from 52 patients with TSCC and 48 age (+/-5 year)/gender-matched controls with benign tonsillar hyperplasia. Results were correlated with HLA-DRB1 haplotype and clinical outcome. HPV was identified in 46% of patients with TSCC and 6% of controls. DNA sequencing showed the presence of HPV type 16 in 21 patients (40%) with TSCC. There was no statistically significant association between HLA-DRB1 expression and TSCC or HPV infection. Fifteen of 16 patients with HPV-positive TSCC with regional metastases had evidence of HPV in pathologically involved lymph nodes. In eight HPV 16-positive TSCC patients with lymph node metastasis, PCR testing identified HPV 16 in 17 of 23 histologically negative lymph nodes. Patients with HPV-positive TSCC without metastatic disease had no evidence of HPV in their lymphatic tissue. Clinically, HPV-associated carcinoma was present in younger patients in comparison with HPV-negative TSCC patients (mean age, 56.6 versus 66 years; P = 0.001). The odds for patients with HPV infection to develop TSCC were 18.2 times greater than for patients without HPV infection (95% confidence interval 4.6, 73.1). There was no statistically significant association between presence of HPV and cause-specific survival (hazard ratio = 2.5 for HPV negative versus positive; P = 0.26), after adjusting for age in a Cox proportional hazards regression analysis. HPV is an independent risk factor for TSCC. Identification of HPV in the histologically positive and negative lymph nodes of patients with HPV-positive TSCC/metastatic disease supports the role of HPV in the oncogenesis of TSCC.