We studied a panel of mutant viruses containing wild-type and chimeric capsid HPV16 and HPV18 proteins. The mutant capsid protein expression, genome amplification, and episomal maintenance were comparable with the wild-type virus. However, the chimeric viruses varied in their titers from wild-type. We show that the intertypical mutant chimeric capsid viruses, that L2 affects the structure of L1 and that L1 affects the structure of L2 in the virion. These effects were measured using a panel of conformation-dependent neutralizing L1 MAbs and an L2 capsid surface peptide derived neutralizing antibody. These data suggest that variation of one capsid gene not only affects its own structure and antigenicity, but also affects the structure and antigenicity of the other capsid protein. Implications of our data suggest that for the continued effectiveness of a vaccine, variation in both capsid proteins need to be considered and not just the protein the vaccine is directed against.