The RB/p16 Pathway but Not p53 Is Disrupted by High Risk HPV in Penile Squamous Cell Carcinoma
E Stankiewicz, DM Prowse, J Cuzick, L Ambroisine, S Kudahetti, N Watkin, C Corbishley, DM Berney. Queen Mary, University of London, London, United Kingdom; St George's Hospital, London, United Kingdom
Background: Several risk factors have been identified for penile cancer, but its pathogenesis is not well understood. Human papillomavirus (HPV) may be involved in the carcinogenesis of penile squamous cell carcinoma (PSCC), yet few studies have compared the cell cycle protein expression in HPV positive and negative cancers of this type. We hypothesized that the types of human papillomavirus infection in different histological types of PSCC and would impact on the expression of key cell cycle proteins: p53, p21, p16INK4A and RB.
Design: We collected 148 samples of PSCC including 97 usual type SCCs, 17 basaloid, and 15 verrucous carcinomas, from patients treated at St George's Hospital between years: 2000-2007 and prepared tissue microarrays. Samples were analysed for RB, p16INK4A, p53 and p21 protein expression by immunohistochemistry. 102 cases were typed for HPV by a broad-spectrum HPV PCR method using SPF10 primers which amplify a 65-bp fragment of the L1 open reading frame and HPV genotypes identified by the INNO-LiPA line probe assay.
Results: HPV DNA was present in 56% of tumours with HPV16 being the most prevalent type. HPV16 was the most common type detected in46/111 cases. Marked differences were observed in HPV prevalence between tumour types with HPV16 detected in 10 cases out of 13 where HPV was detected. 9 other types of HPV were detected including types 11, 31 and 33, but no HPV18. RB protein negatively (p<0.0001) and p16INK4A and p21 positively correlated (p<0.0001) with high-risk HPV infection. There was a significant difference in RB and p16INK4A expression between usual type, basaloid and verrucous tumours(p<0.0001). No correlation was found between HPV or tumour type with p53 protein expression.
Conclusions: HPV infection is present in over half of penile cancers and appears to be responsible for RB pathway disruption in those tumours. However, no link between high-risk HPV types and p53 immunodetection was found. Different histological types of PSSC express differnt HPV DNA subtyoes, confirming possible separate aetiologies for those tumours. We confirm that usual type PSCC seems to have at least two different aetiologies: one related to HPV and one unrelated. We suggest that use of the bivalent HPV16/18 prophylactic vaccine in men could reduce occurrence of penile SCC by only 45%.
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 11:00 AM
Platform Session: Section A, Tuesday Morning