Squamous cell carcinoma (SCC) in the genital region is recognized to be caused by human papillomavirus (HPV) infection. Although SCC of the nail apparatus have been reported to be associated with high-risk HPVs, this fact is not widely known in general medicine, and systemic analyses have not been performed. The purpose of this study was to clarify the HPV infection in the nail apparatus in our department and summarize previous data from the literature.

We collected 106 samples of SCC/SCC in situ and performed polymerase chain reaction using HPV consensus primers and subsequent direct DNA sequencing. We performed immunohistochemistry (IHC) using an anti-HPV L1 antibody. We also reviewed 136 cases of HPV-associated nail SCC/SCC in situ in the literature in order to reveal the clinical characteristics. 

Two cases of genital SCC and 9 cases of SCC in situ were high-risk HPV positive . Of note, 6 HPV-positive cases were nail SCC in situ. In those cases, numerous HPV-positive cells were observed around the nail fold, especially in the nail matrix. HPV-positive cells are distributed even in the epithelial cells of the proximal nail fold, suggesting that the HPV infection spreads beyond the clinically visible lesion. On reviewing the previous literature of nail SCC, the patients’ ages ranged from 12 to 85 years old (average age 52.2 years old), and the sex ratio was 2.3:1 (92 males and 39 females). About half of cases were positive for high-risk HPV. The disease had male dominance, and left digit 3 and right digits 1-3 were frequently affected. Multiple lesions were seen in 11 patients. In this review, 24% of the cases of nail SCC had a history of other HPV-associated diseases, suggesting the possibility of genito-digital transmission. 

In this study, we showed that the nail apparatus is a characteristic region for high-risk HPV infection. Based on this analysis, we propose that nail SCC is a high-risk HPV-associated reservoir site for sexually transmitted infection.

Detection of high-risk human papillomavirus in nail squamous cell carcinoma and comprehensive analyses of 136 cases from the literature: The implications for high-risk human papillomavirus reservoir and sexually transmitted infection