Diversity of human papillomavirus types in periungual squamous cell carcinoma

P>Background There is accumulating evidence that infections with certain high-risk alpha-human papillomaviruses (HPVs) are involved in the pathogenesis of digital squamous cell carcinomas (SCCs) and their precursor lesions (SCCs in situ). Objectives This study was initiated to search for alpha- and beta-HPV infections in a collective of SCC and SCC in situ located on the hands. Methods HPV typing for 36 high-risk and low-risk alpha-HPV types and 25 beta-HPV types was performed in SCCs located at different sites of the hands. Additionally, immunohistochemical staining for p16INK4a and Ki67 was performed in 15 samples. Results In total, 25 SCCs/SCCs in situ (six periungual lesions, eight lesions from the proximal or lateral part of the finger, and 11 lesions from the dorsal part of the hand) were analysed for the presence of alpha- and beta-HPV types. Only one lesion (an SCC in situ positive for HPV11 and HPV31) of the dorsal hand and none of the proximal or lateral part finger lesions were alpha-HPV positive. In contrast, all six periungual lesions were alpha-HPV positive, and the majority (83%) of them carried HPV types other than HPV16 (HPV26, HPV33, HPV51, HPV56 and HPV73). beta-HPV types were found in only two biopsies. p16INK4a and Ki67 expression was significantly higher in HPV-positive lesions as compared with HPV-negative tumours, and both markers significantly correlated with each other. Conclusions In contrast to other locations of the hands, periungual SCCs are frequently associated with alpha-HPV infections. Several high-risk HPV types other than HPV16 can induce periungual SCCs. Given the high recurrence rate and high proliferative activity of HPV-associated periungual SCCs, aggressive treatment and close follow-up of these tumours is mandatory.