Increased expression of matrix metalloproteinase‐2 and 9 and human papilloma virus infection are associated with malignant transformation of sinonasal inverted papilloma

BACKGROUND AND OBJECTIVES: In this study, we identified matrix metalloproteinase (MMP)-2 and 9 expression in exophytic papilloma (EP), inverted papilloma (IP) with dysplasia, IP with carcinoma, and invasive squamous cell carcinoma (SCC). We also compared the presence of MMP-2 and 9 with human papilloma virus (HPV) infection. METHODS: The nasal tissue were stained with monoclonal antibodies to MMP-2 and 9. The results were analyzed using quantitative immunohistochemical analysis. In situ hybridization studies for HPV DNA for 6/11, 16/18, and 31/33 were also performed on the tissue. RESULTS: Significant increase of MMP-2 and 9 were observed in IP with moderate and severe dysplasia, IP with carcinoma, and invasive SCC compared to control nasal mucosa. Among IP, HPV 6/11-positive was present in 41% and HPV 16/18-positive was present in 31%. In HPV 6/11 and 16/18-positive IP, significant increase of MMP-2 and 9 were observed. CONCLUSIONS: Precancerous lesions of IP exhibited elevated levels of MMP-2 and 9 and these expression may be associated with early events in IP carcinogenesis. HPV infection would be an early event in a multistep process of malignant formation of IP.