Diabetic Foot Ulcer Calluses Show Histological Similarities to HPV Infection Without Evidence of HPV Involvement by Nested PCR

Abstract

A number of studies have reported an association between callus formation and the development of foot ulcers in diabetic patients. However, it has been noted that calluses may continue to form in spite of bed rest and, presumably, excellent patient compliance with offloading. Additionally, the authors have noted that, histologically, calluses in the diabetic foot often resemble lesions induced by human papillomavirus (HPV). As diabetes is associated with immune depression, the authors hypothesized that HPV may play at least a partial role in the pathogenesis of calluses in diabetic patients. The objective of the reported study was to determine whether calluses around diabetic neuropathic foot ulcers are associated with HPV infection. The authors carried out biopsies on 11 independent calluses from 6 patients with diabetic foot ulcers and analyzed each sample by histology and by nested polymerase chain reaction (PCR), screening for the presence of DNA from HPV-1, -2, -3, -4, -6, -10, -11, -16, -18, -27, -28, -29, -31, -41, -50, -57, -60, -63, -65, and -77. The callus biopsy specimens showed histological evidence of koilocytes, papillary hyperplasia, hypergranulosis, and hyperkeratosis, a picture very similar to HPV cutaneous infection. However, nested PCR using positive and negative controls did not show detectable levels of HPV DNA. The authors therefore conclude that HPV infection is unlikely to play a significant role in diabetic foot callus pathogenesis, in spite of histological findings similar to those seen with verruca vulgaris.