Tissue effects of and host response to human papillomavirus infection

Human papillomaviruses are a heterogeneous group of DNA tumor viruses associated with hyperplastic (warts, condylomas), dysplastic (CIN and VIN), and malignant lesions (carcinomas) of squamous epithelium. Each HPV type is preferentially associated with specific clinical lesions and has an anatomic site preference for either cutaneous or mucosal squamous epithelium. Infection appears to begin in the basal cells. Early gene expression is associated with acanthosis, and late gene expression is associated with appearance of structural antigens and virions in nuclei of cells of the granular layer, usually koilocytotic cells. Malignant transformation of warts and papillomas appears to be related to a variety of factors: (1) infection by certain HPV types (HPV-5, HPV-8, HPV-16, HPV-18, HPV-31); (2) decreased cellular immunity to HPV-associated antigens; and (3) interaction with cofactors, such as other microorganisms or sunlight (see also the article by Kashima and Shah). Spontaneous regression or successful treatment of the benign lesions appears to depend on either naturally acquired or iatrogenically related stimulation of HPV type-specific immunity. The humoral antibody response to HPV particles may be important in preventing infection. In contrast, the local events surrounding regression of warts and condylomas are primarily associated with specific cell-mediated immunity. Local cell-mediated immune responses, particularly cell-associated soluble mediators and stationary macrophage-like cells, may be especially important in the host's immune response to mucosal infections.