Deregulation of E‐cadherin by human papillomavirus is not confined to high‐risk,cancer‐causing types

Background E‐cadherin is a tumour suppressor protein, which is normally expressed on keratinocytes and antigen‐presenting Langerhans cells (LCs) in the epidermis. We have previously shown that E‐cadherin is lost from tissues infected with the high‐risk cancer‐causing human papillomavirus (HPV) type 16. Objectives To test if E‐cadherin dysregulation is associated with the cancer risk of the infecting HPV and to establish if it is conserved among HPVs in the α, β, γ and μ genera. Methods Forty‐seven lesions infected with low‐ or high‐risk HPV types spanning four HPV genera were stained for E‐cadherin, P‐cadherin and CD1a to detect LCs. Results Surface E‐cadherin was reduced in tissues infected with members of the α4, α7 and α9 species and the γ and μ genera but was equivalent to normal epidermis in the β only‐infected lesions tested and patchy in α10‐infected tissues. There was a direct relationship between atypical E‐cadherin expression and a significant reduction in LCs. Expression of P‐cadherin, a protein that is increased in the E‐cadherin constitutive knockout mouse, was increased in lesions with reduced E‐cadherin. Conclusions These data show that E‐cadherin dysregulation by HPV is widely conserved across the majority of HPV genera. E‐cadherin expression was reduced or lost in epidermis irrespective of the cancer risk of the infecting HPV type or the ability of the virus to degrade retinoblastoma protein or p53. A correlation between dysregulated E‐cadherin and reduced numbers of LCs supports viral regulation of surface E‐cadherin contributing to viral evasion of the host immune system.