p53 alteration and human papilloma virus infection in paranasal sinus cancer

BACKGROUND. Inverted papilloma (IP) of the paranasal sinus is a benign neoplastic condition that can be associated with squamous cell carcinoma (SCC). To understand the etiology of the disease better, paranasal sinus tumor specimens were examined for alterations in either p53 protein expression or genomic DNA sequence, and for infection by human papilloma virus (HPV). METHODS. Tumor specimens were categorized as follows: benign, nondysplastic IP; IP with dysplasia; SCC arising within IP; or SCC without IP. Sections of each tumor specimen were stained for p53 protein overexpression, and mutations in exons 5-9 of the p53 gene were determined in DNA purified from all tumor samples. HPV infection was screened by degenerate polymerase chain reaction (PCR) amplification and typed by multiplex PCR and direct DNA sequencing of PCR-amplified HPV sequences. RESULTS. Altered p53, either in genetic sequence or protein overexpression, was observed in 0 of 7 benign, nondysplastic IP specimens. A significantly higher p53 alteration incidence was observed for IP specimens exhibiting dysplasia (57%; P < 0.05) and IP specimens that were associated with SCC (75%; P < 0.025). HPV sequences were detected in 9 of 24 (38%) tumor specimens, 78% of which were of the oncogenic HPV16 strain. A significantly higher incidence (P < 0.05) of HPV infection was observed in IP tumors exhibiting dysplasia or containing SCC than in nondysplastic IPs. None of the p53-mutated tumors were infected with oncogenic HPV16. CONCLUSIONS: These data suggest that p53 alterations and/or HPV infection are associated predominantly with IPs exhibiting evidence of dysplasia or IPs associated with SCC, but not in nondysplastic, benign IPs. In addition, an inverse correlation may exist between oncogenic HPV infection and p53 alterations in paranasal sinus tumors. The authors postulate that patients with IPs containing altered p53 may be at increased risk for SCC of the paranasal sinus.