Transcriptional Activity of HPV in Inverted Papilloma Demonstrated by In Situ Hybridization of HPV mRNA

Abstract

Objectives: (1) Demonstrate the incidence of human papillomavirus (HPV) transcriptional activity in inverted Schneiderian papilloma (IP). (2) Evaluate the role of HPV in the pathogenesis of IP and its rare progression to malignancy. (3) Support the consideration of RNAscope in diagnosis and management of IP. Methods: Retrospective clinical and histopathologic review of 20 cases of IP who underwent surgical excision at a tertiary referral center between 1995 and 2013. Surgical pathology archival material was re-examined histopathologically using H&E slides. Formalin-fixed paraffin-embedded material from each case was further evaluated using immunohistochemical staining for p16 as well as in situ hybridization (ISH) for HPV E6/E7 mRNA (RNAscope). Results: Patients were 40% female with average age 53.7 years (range, 23-82 years). Three had evidence of malignancy at the time of excision, and 5 demonstrated recurrence of IP. Average follow-up was 48 months (range, 0-200 months), and one patient died from squamous cell carcinoma (SCC) arising from the IP. HPV transcriptional activity noted by RNAscope within specimens is reported. Conclusions: These data serve to aid in clarification of conflicting prior research attempting to establish a connection between the presence of HPV and development of IP. By demonstrating transcriptional activity of HPV in IP, this connection is rendered more definitive. Further studies are necessary to elucidate the mechanism by which this process occurs, and what, if any, impact HPV status has on progression from IP to SCC.