P53 ALTERATION AND HUMAN PAPILLOMA-VIRUS INFECTION IN PARANASAL SINUSCANCER

BACKGROUND. Inverted papilloma (IF) of the paranasal sinus is a benign neoplastic condition that can be associated with squamous cell carcin oma (SCC), To understand the etiology of the disease better, paranasal sinus tumor specimens were examined for alterations in either p53 pro tein expression or genomic DNA sequence, and for infection by human pa pilloma virus (HPV). METHODS. Tumor specimens were categorized as foll ows: benign, nondysplastic IF; IP with dysplasia; SCC arising within I F; or SCC without IF. Sections of Each tumor specimen were stained for p53 protein overexpression, and mutations in exons 5-9 of tile p53 ge ne were determined in DNA purified from all tumor samples. HPV infecti on was screened by degenerate polymerase chain reaction (PCR) amplific ation and typed by multiplex PCR and direct DNA sequencing of PCR-ampl ified HPV sequences. RESULTS. Altered p53, either in genetic sequence or protein overexpression, was observed in 0 of 7 benign, nondysplasti c IP specimens. A significantly higher p53 alteration incidence was ob served for IP specimens exhibiting dysplasia (57%; P < 0.05) and IP sp ecimens 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 t ile oncogenic HPV16 strain, A significantly higher incidence (P < 0.05 ) of HPV infection was observed in IP tumors exhibiting dysplasia or c ontaining SCC than in nondysplastic IPs. None of the p53-mutated tumor s 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 correla tion may exist between oncogenic HPV infection and p53 alterations in paranasal sinus tumors. The authors postulate that patients with IPs c ontaining altered p53 may be at increased risk for SCC of the paranasa l sinus. (C) 1997 American Cancer Society.