Mucosal immunoglobulin-A and -G responses to oncogenic human papilloma virus capsids

Oncogenic human papilloma virus (HPV) infection is the most important risk factor for developing cervical cancer. It is known that serum antibody responses against these viruses are associated with persistent infection. We conducted an epidemiological study of 627 women to detect cervical mucosal immunoglobulin (Ig)A and IgG responses to oncogenic HPV capsids. Antibody reactivity and cervical HPV infection genotypes were examined by enzyme-linked immunosorbent assay (ELISA) using HPV types 16, 18, 31, and 45 virus-like particles, and a polymerase chain reaction-based method, respectively. HPV infection was defined as being positive for HPV DNA. Multivariate analysis revealed that a mucosal IgA response was associated with the HPV infection, whereas the IgG response was associated with high-grade cervical squamous intraepithelial lesions (SIL)/squamous cell cancer (SCC) and subject age (40-49 years). IgA was positive in 72% of women with oncogenic HPV infections, whereas IgG was positive in 64% of women with high-grade SIL/SCC. The longitudinal study demonstrated that the IgA response was elicited earlier than the IgG response, and the IgG response was barely induced in the preclinical HPV infection. However, once an IgG response was induced, it persisted longer after HPV clearance. The mucosal IgA response reflects current HPV infection, whereas an IgG response may be induced with the development of cervical lesions.