Human papillomaviruses (HPV) are increasingly associated with a range of cancers of the epidermis including head and neck cancer, in addition to their role as the primary causal agent of cervical cancer. HPV causes persistent infections that spontaneously regress in many cases, as a result of an adaptive immune response to the virus. In HPV infection, initiation of the immune response has been thought to involve the antigen presenting cells of the epidermis, the Langerhans cells, which are reported to be highly efficient at antigen uptake and presentation in vitro.
Here we discuss the immune regulatory effects of the HPV16 oncoproteins on Langerhans cells. Data describing the effects of E6 and E7 on function are reported, with particular focus on CD8+ cytotoxicity. Our findings show that E6 regulates cell-to-cell adhesion and that E7 is important in suppression of the CD8 T cell response in the skin. Langerhans cells also are suppressed when co-cultured with microparticles from E7-expressing keratinocytes.
There is mounting evidence supporting regulation of Langerhans cells by HPV16, however E7 suppression of the immune response can occur in the absence of Langerhans cells in the mouse. In addition, regulation of Langerhans cells gene expression in E7-expressing skin is altered in the presence of Candida antigen, suggesting that other factors in the microenvironment also impact on E7 regulation of these genes.