Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcinoma.
BACKGROUND
Human papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer.


OBJECTIVE
To investigate the role of HPV infection and expression of the tumour suppressor protein p16INK4A in the pathogenesis of penile cancer.


METHODS
By means of polymerase chain reaction amplification and reverse hybridization line probe assay to detect HPV infection, and immunohistochemical staining for p16INK4A and Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent penile lichen sclerosus (LS) lesions from 46 patients.


RESULTS
HPV DNA was found in 54% of penile SCCs and 33% of penile LS cases in single and multiple infections. High-risk HPV 16 was the predominant HPV type detected. No relationship between Ki67 expression and HPV infection was observed. Strong immunostaining for p16INK4A correlated with HPV 16/18 infection in both penile LS and penile SCC. In our penile SCC series the cancer margins were also associated with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC cases associated with LS and in six of the 11 SCC lesions not involving LS.


CONCLUSIONS
Our study shows a high prevalence of HPV 16 and p16INK4A expression in penile lesions, consistent with an active role for HPV in interfering with the retinoblastoma pathway. High-risk HPV infection could be involved in the tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV vaccines has the potential to prevent these cancers.
Centre for Molecular Oncology, Institute of Cancer, Bart's and The London Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK. d.m.prowse@qmul.ac.uk
D M
DM
Prowse
E N
EN
Ktori
D
D
Chandrasekaran
A
A
Prapa
S
S
Baithun
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D018459:Lichen Sclerosus et Atrophicus / Q000378:metabolism*; D008297:Male; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism*; D010409:Penile Diseases / Q000378:metabolism* / Q000821:virology; D010412:Penile Neoplasms / Q000378:metabolism / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000821:virology
D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen