Histological analysis suggests that inverted papilloma (IP) tumorigenesis may occur through a stepwise series of discrete events. The association between human papilloma virus (HPV) and IP has been described at varying incidences. The purpose of this study was to evaluate the prevalence of the HPV subtypes in a large series of IP specimens classified by histological grade. Fifty-seven paraffin-embedded specimens of Korean population were available for study. Each specimen was graded according to a four-stage histological grading system (stages I and II, benign IP; stage III, dysplastic IP; stage IV, carcinoma arising from IP). A representative section of IP specimen was isolated through laser capture microdissection (7.5- to 10-mum laser spot size). Subsequently, DNA extraction and HPV genotyping with the HPV DNA chip test (Biomed Lab Co., Seoul, Korea) was performed. The HPV DNA chip contained 22 type-specific probes that consisted of 15 high-risk subtypes and 7 low-risk subtypes. Histological grading was as follows: 5, grade I; 23, grade II; 22, grade III; and 7, grade IV. Seven of 57 specimens (12.3%) showed HPV DNA. All of the HPV(+) cases showed HPV DNA in early grade (grades I and II) IP lesions. No higher grade (grades III and IV) IP tumors showed HPV DNA. Among the seven HPV(+) cases, five were high-risk subtypes and two were unspecified subtypes. HPV infection, mainly high-risk subtypes, occurs in benign IP as an early event during the multistep tumorigenesis of IP. Cumulative other genetic insults may be required to progress from benign IP (grades I and II) to dysplastic IP (grade III) and carcinoma arising from IP (grade IV).

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