Linkage of regression and malignant conversion of rabbit viral papillomas to MHC class II genes

Human papillomaviruses associated with cutaneous and anogenital cancers induce intraepithelial precursor lesions which may regress spontaneously or progress into invasive carcinomas. Cell-mediated immune responses are probably involved in regression of precancerous lesions and the polymorphism of the genes responsible may thus have a key role in the variability of the host response. Skin warts and cancers induced in rabbits by Shope papillomavirus provide a model to test this hypothesis. We analysed a restriction-fragment-length polymorphism of major histocompatibility complex class I and class II genes and T-cell receptor beta-chain genes in infected domestic rabbits. We found a strong linkage between wart regression and a DR alpha EcoRI fragment, and an increased relative risk of malignant transformation associated with a DQ alpha PvuII fragment. This indicates a genetic control of wart evolution, involving genes in the class II region of the major histocompatibility complex.