Human papillomaviruses (HPV), especially the
epidermodysplasia verruciformis (EV)-associated HPV 5, 8, 14, 17, 20, and 47, are thought to play a role in the pathogenesis of some
skin cancers in recipients of renal allografts. MHC class I and class II genes are involved in the cellular immune response to viral and
tumor Ag. Little is known about humoral responses to HPV in recipients with and without
skin cancer. We investigated the prevalence of
antibodies to the early (E)
protein E7 and the major capsid late (L)
protein L1 of HPV 8. In addition, we studied the association of HLA class II molecules with these antibody responses. The E7 and L1 open reading frames of HPV 8 were bacterially expressed as
beta-galactosidase fusion
proteins, which were purified by preparative gel electrophoresis. Serum samples from 36 renal transplant recipients with and 91 recipients without
skin cancer were screened for the presence of
IgG and
IgM antibodies to HPV 8 E7 and L1, by Western blot analysis. The detection of anti-HPV 8 L1
antibodies represents the immune response to HPV 8 and possibly other EV-associated HPV, because cross-reactivity between the representatives of this HPV subgenus can occur. The antibody responses to HLA Ag were used as controls. Recipients who had
IgM antibodies but no
IgG antibodies to L1 of HPV 8 (patients with no apparent class switch from
IgM to
IgG) had
skin cancer in 50% of cases, whereas recipients who produced
IgG antibodies (patients with an apparently good humoral response to L1 of HPV 8) had
skin cancer in only 18% of cases. The estimated relative risk of
skin cancer in recipients with no class switch, compared with the risk in those with a good humoral response, was 4.5 (95% confidence interval, 1.1 to 18.1). We found no association between the antibody response to HLA Ag and the occurrence of
skin cancer. A strong linkage between the absent class switch of antibody production in response to L1 of HPV 8 and
HLA-DR7 was observed (relative risk, 26.2). Renal transplant recipients who have no apparent class switch from
IgM to
IgG production in response to Ag encoded by L1 of HPV 8 or possibly other EV-associated HPV are at an increased risk of
skin cancer. The association with
HLA-DR7 indicates a genetic control of
skin cancer development or regression, involving genes in the class II region of the MHC.