New biomarkers of human papillomavirus infection in epidermodysplasia verruciformis

Ann Diagn Pathol. 2019 Jun:40:81-87. doi: 10.1016/j.anndiagpath.2019.04.010. Epub 2019 Apr 23.


The cause of epidermodysplasia verruciformis is infection by human papillomavirus, usually types 5 or 8, and it exhibits a high potential for malignant transformation. The diagnostic histologic features of epidermodysplasia verruciformis are not always present and can be mimicked by non-viral diseases. The purpose of this study was to interrogate such lesions for new potential biomarkers to aid in the diagnostic accuracy. HPV DNA was high copy and localized to the upper half of the lesion in cells with cytologic features that included perinuclear halos, blue-grey cytoplasm, and hyper/parakeratosis. Serial section analyses demonstrated that there was increased expression of importin-β, exportin-5, Mcl1, p16, Ki67 and PDL1 in 13/13 epidermodysplasia verruciformis lesions. Each of these proteins localized primarily to the less differentiated cells in the parabasal aspect of the lesion. Only Ki67 and exportin-5 were expressed in the normal epithelia, though much less so, in 13/13 aged matched controls. It is concluded that the host response to HPV 5/8 infection in epidermodysplasia verruciformis includes the up regulation of several proteins including p16, Ki67, importin-β, exportin-5, Mcl1, and PDL1. Thus, these proteins may serve as new biomarkers of this disease that can aid in cases that are equivocal for epidermodysplasia verruciformis on histologic examination.

Keywords: EDV; Exportin; HPV; Importin; Mcl1; PDL1.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / analysis*
  • Cell Transformation, Neoplastic
  • Epidermodysplasia Verruciformis / diagnosis*
  • Epidermodysplasia Verruciformis / pathology
  • Epidermodysplasia Verruciformis / virology
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Young Adult


  • Biomarkers