Results of the first WHO international collaborative study on the standardization of the detection of antibodies to human papillomaviruses.

Detection of genotype-specific human papillomavirus (HPV) capsid antibody in serum suggests past HPV infection. Also, these antibodies appear to correlate with vaccine-induced protection against infection, at least in animal models. However, each laboratory defines a reactive result differently and there is no agreed definition of what level of response indicates sero-reactivity. Standardization of assays for HPV capsid antibody will therefore assist with HPV vaccine development and epidemiology. This study was undertaken to investigate the specificity and sensitivity of assays in current use for measuring antibody to the major viral capsid protein L1 of HPV. Ten laboratories from 8 countries each analyzed 12 coded serum samples, which were derived from an uninfected woman, from naturally infected women and from individuals immunized with different vaccine candidates currently under clinical development. Study samples were assayed by methods in routine use in the participating laboratories. Nine assays were based on virus-like particles (VLPs) of 1 or more HPV genotypes. One laboratory used bacterially expressed major capsid protein L1 of HPV genotypes as antigen. There was considerable interlaboratory variation in estimated antibody levels. However, ranking of the potency of HPV 16 reactivity across the 12 test sera was consistent for all 10 laboratories. Expression of HPV 16 antibody levels relative to that of a single serum sample from an HPV16-infected woman considerably improved the interlaboratory assay comparability. Establishment of an International Standard for antibodies to HPV 16 would therefore facilitate the comparison of HPV antibody measurements between laboratories and assays.