Human Papillomavirus and Epstein-Barr Virus in Sinonasal Schneiderian Papillomas: An In Situ Hybridization and Polymerase Chain Reaction Study

Using the polymerase chain reaction (PCR), it has been recently reported that the Epstein-Barr virus (EBV) is present in the majority of Schneiderian sinonasal papillomas (SNP) of the inverted type and may play a role in the pathogenesis of these lesions. The reported prevalence rates of human papillomavirus (HPV) in different types of SNP is also controversial and in need of clarification. Twenty-eight SNP from 27 patients were histologically classified and evaluated for evidence of EBV using PCR and 2 different sensitive and specific in situ hybridization (ISH) procedures for EBER1. Similarly, two methods of ISH were also used for the detection of HPV, using biotinylated DNA probes sensitive for 14 different HPV types as well as more sensitive and specific radioactive RNA probes for HPV types 6, 11, and 16. Polymerase chain reaction was successful in 19 papillomas, including 12 of 19 inverted SNP, 1 of 1 inverted SNP with squamous cell carcinoma, 4 of 5 fungiform SNP, and 2 of 3 oncocytic lesions. Southern blot hybridization of PCR products showed the presence of EBV DNA in two lesions, including one inverted SNP and the single inverted SNP with squamous cell carcinoma. By both DNA- and RNA-mRNA ISH, positivity for The nasal cavity and paranasal sinuses are predominantly lined by ciliated columnar epithelium referred to as the Schneiderian membrane, which develops as an invagination of olfactory ectoderm during the fourth week of embryonic development.1 This mucosa creates a transitional zone between the endodermally derived respiratory epithelium of the nasopharynx and the keratinizing squamous epithelium of the nasal vestibule. Three Schneiderian papillomas (SNP) arise from this unique mucosal lining, including inverted, fungiform, and oncocytic (cylindrical cell) types. From the 'Departments of Pathology. The University of Virginia Health Sciences Center. Charlottesville. Virginia; and 2The City of Hope National Medical Center. Duarte. California. Supported in part by grant #ROI-CA43629 from the Public Health Service to Mark H. Stoler. Manuscript received March 25, 1996; accepted April 29, 1996. Address reprint requests to Dr. Gaffey: Box 214, Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville, VA 22908. EBER was detected in rare stromal lymphocytes but not the overlying epithelium in the inverted SNP with SCC. The remaining cases, including the other inverted SNP positive for EBV by PCR, were completely negative by both ISH techniques. Human papillomavirus was detected by ISH in 1 of 19 (5%) inverted, 1 of 1 (100%) inverted with squamous cancer, 5 of 5 (100%) fungiform, and 0 of 3 (0%) oncocytic SNP. Three SNP contained HPV 6 (all fungiform), three SNP labeled for HPV 11 (two fungiform and the inverted SNP with squamous cancer), and one inverted SNP contained HPV 16. Of the five fungiform SNP, four showed foci of koilocytosis. The results indicate that EBV is not present in sinonasal papillomas. The presence of EBV positive stromal lymphocytes in these lesions may account for a proportion of PCR-positive cases. Oncocytic SNP are unassociated with HPV, whereas inverted SNP contain HPV in a minority of cases. In contrast, fungiform SNP are consistently associated with HPV types 6 and 11 and usually show histologic evidence of viral infection.