579 High-risk human papillomavirus infection in Bowen’s disease and Squamous Cell Carcinomas of the hands

Abstract

High-risk (HR) mucosal human papillomaviruses (HPV) are implicated as causative agent in the development of some cutaneous cancers, in particular squamous cell carcinomas (SCC) of the hands. Reported prevalence rates of HR HPV vary from 0-89%. We investigated archived tissues (28 Bowen’s disease (BD) and 9 SCC of the hands) for the presence of HR HPV DNA and the prevalent genotype by real-time PCR. Expression of p16, p53, and epidermal growth factor receptor (EGFR) was determined by immunohistochemistry and data analysed using the HistoQuest software. Viral DNA was detected in 61% of the tumors tested (BD: 54%, SCC: 33%) with HR HPV16 being the predominant type (73%), followed by 33, 52, and, in an HIV-infected patient, the rare type 26. The vast majority of the tumors was p16-positive and no significant difference was observed between virus-positive and -negative entities (82 vs. 100%, respectively). Few cases of BD (12%), which were negative for viral DNA, but not any of SCC stained positive for p53. EGFR-positivity was detected in 36% of BD and 11% of SCC and not linked to viral DNA status. Here we provide additional evidence for the etiological role of mucosal HR HPV in the development of cutaneous BD and SCC of the hands in immunocompetent patients. In contrast to HR HPV-induced cancers of the anogenital and oropharyngeal tract, p16 expression was not associated with HPV DNA positivity and, hence, does not represent a good surrogate marker for HR HPV infection in skin tumors. Limited expression of mutated p53 was observed in some virus-negative tumors, indicating a causative involvement of UV light adjunct to HR HPV infection. Given the rare EGFR expression in the SCC of the hands, EGFR inhibition does not seem to represent a suitable therapeutic option for this subset, however, more studies encompassing a higher number of tumors are warranted. Taken together, our findings suggest that BD and SCC of the hands represent a distinct entity within cutaneous cancers.