[Molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses]

Abstract

Nasal inverted papilloma (IP) is a rare benign tumor that involves the mucous membranes of the nasal cavity and paranasal sinuses. Postoperative recurrences of this tumor have been observed frequently, and an association with squamous cell carcinoma (SCC) has been described occasionally. The etiology of IP remains unknown, but some studies have suggested a possible causative role of human papillomavirus (HPV) in IP. To determine the etiological role of HPV in IP and SCC associated with IP, to clarify the relationship between HPV and malignant transformation of IP, and to study the possibility of HPV implication in SCC of the nasal cavities and paranasal sinuses, retrospective analysis of HPV infection was performed in the surgically resected specimens of inverted papilloma (n = 26, in which 7 patients had SCC) and SCC (n = 40) of the nasal cavities and paranasal sinuses. Pathologically, koilocytosis, which is known to be closely related to HPV infection, and epithelial atypia were investigated. To detect the HPV protein antigen or nucleic acids, immunohistochemical method and molecular pathologic techniques, or in situ hybridization (ISH) and polymerase chain reaction (PCR) of DNA extracted from paraffin embedded tissues were used. By ISH we detected HPV 11 DNA in three cases (12%) of IP and HPV 16 DNA in one case (4%) of IP with SCC. By PCR HPV16 was detected in 2 of 7 cases in which IP was associated with SCC. However, no protein antigen was detected in any cases of IP by immunostaining, and viral mRNA was not detected by the study of ISH after DNase digestion. Pathologically, there was a closed relationship between HPV infection and koilocytosis, and severe epithelial atypia was frequently seen in the cases of IP coexisted with SCC. But there was no clear relationship between HPV infection and recurrence of IP. In SCC, HPV 16 and HPV 18 were detected by PCR in 4 cases (10%) and in one case (2.5%), respectively. Thus, it was suggested that HPVs were involved in the development of IP in some cases (19%, 5/26), but the state of infection is somewhat different from other papillomatous lesions, such as genital condylomas or laryngeal papillomas. HPV 16 and HPV 18 were found to be related to the malignant transformation of IP and to the pathogenesis of SCC originated in the nasal cavities and paranasal sinuses.