The RB/ p16INK4A pathway but not p53 is disrupted by human papillomavirus in penile squamous cell carcinoma

Aims: The Pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood. Human papillomavirus (HPV) may be involved in carcinogenesis, but few studies have compared cell-cycle protein expression in HPV positive and negative cancers. The aim was to determine the extent of HPV infection in different histological subtypes of PSCC and its impact on the expression of key cell cycle proteins: p53, p21, p16INK4A and RB. Methods and Results: We examined 148 PSCC samples immunohistochemically for RB, p16INK4A, p53 and p21 protein expression. 102 cases were typed for HPV by PCR. HPV DNA was detected in 56% of tumours with HPV16 present in 81%. Basaloid tumours were strongly related to HPV infection (10/13) while verrucous were not (3/13). Fifty-nine % (38/64) of usual type SCCs had HPV infection. RB protein negatively (p<0.0001) and p16INK4A (p<0.0001) and p21 (p=0.0002) positively correlated with HPV infection. p53 did not correlate with HPV infection. Conclusions: HPV infection is present in over half of penile cancers and it is responsible for RB pathway disruption. However, no link between HPV and p53 immunodetection was found. Only basaloid and half of usual type PSSCs correlate with HPV, confirming possible separate aetiologies for those tumours.