Human Papillomavirus Is Not an Etiologic Agent of Urothelial Inverted Papillomas
Riley E Alexander, Antonio Lopez-Beltran, Rodolfo Montironi, Gregory T MacLennan, Eva Comperat, Liang Cheng. Indiana University School of Medicine, Indianapolis, IN; Cordoba University, Cordoba, Spain; Polytechnic University of the Marche Region, United Hospitals, Ancona, Italy; Case Western Reserve University, Cleveland, OH; Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Background: Inverted papilloma of the urinary bladder is rare, accounting for less than 1% of all bladder neoplasms. Though it was long believed to be a pre-malignant neoplasm, there is a growing consensus that it is a benign lesion with limited potential for recurrence. Its etiology has been a matter of controversy, and recently it has been suggested that human papillomavirus (HPV) may play a role in its development. To date, this hypothesis has not been adequately substantiated. The goal of this study was to evaluate a number of inverted papillomas of the urinary bladder to investigate a possible etiologic role of HPV, employing an in-situ hybridization technique.
Design: We studied urinary bladder inverted papillomas from 27 patients ranging from 35-78 years of age (average age 61 years), the great majority of whom were male (M:F ratio of 11:1). HPV in situ hybridization was performed on all cases using Inform HPV II Family 6 Probe (detecting HPV genotypes 6 and 11) and HPV III Family 16 Probe (detecting HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 66) (Ventana Medical Systems, Inc, Tucson, AZ). The cases were then assessed for nuclear expression pattern. A control slide using uterine cervix with established HPV was prepared for each run. p16 immunostaining was performed with the anti-p16 mouse monoclonal antibody using the CINtec Histology kit (CINtec Histology, Westborough, MA, USA).
Results: In all 27 cases, no HPV was detected with either the low-risk or high-risk probes. All controls reacted appropriately and confirmed the lack of HPV within the studied population of inverted papillomas. Immunoreactivity to p16 was detected in 11 of 27 (41%) cases. In six of these cases, staining was seen in greater than 50% of the inverted papilloma tissue; the remaining five cases demonstrated only focal reactivity.
Conclusions: Our study provides no support for the premise that HPV is an etiologic agent in the development of inverted papilloma of the urinary bladder. In addition, correlation of HPV-ISH with p16 immunostaining shows that p16 is not a reliable marker of HPV infection status in inverted papillomas and should not be used as a surrogate marker to determine HPV status in these lesions.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 198, Tuesday Afternoon