Sourcing of the WHO human papillomavirus type 18 international standards for HPV antibody levels

• We were sourcing for candidate IS sera to enhance serology for genital HPVs.
• We analyzed sera from 1007 Thai women (61 cervical cancer cases and 946 healthy women) with Pseudovirion-Luminex serology.
• Thirteen healthy women, who were selected as IS candidates, donated a blood bag.
• Sera from two of women were pooled to became IS for HPV-18.
• Antibodies of HPV-16, -31, -52 and -58 associated with cervical cancer in Thai women.

BackgroundHPV serology is important for studies of vaccine immunogenicity, but can not be performed in a comparable manner without international standardisation.ObjectivesTo find suitable candidate sera from naturally infected persons for use as International Standards (IS) for antibodies to high-risk HPVs, with priority for HPV-18.Study design946 healthy Thai women (median age 44, range 18–83) and 61 cervical cancer patients were screened using an HPV pseudovirion-Luminex assay to detect antibodies to genital (HPV-6,-11,-16,-18,-31,-33,-45,-52,-58,-68) and non-genital HPV types (HPV-5,-15,-32,-38 and -76). Suitable candidate sera should ideally be mono-specific (have reactivity against only one genital HPV) and have high antibody levels that are stable over time.ResultsSeroprevalences of HPV-16,-31,-52 and -58 were at least twice as high among cancer patients compared to healthy individuals. Thirteen healthy women who met the IS inclusion criteria in initial testing also consented to blood-bag donations. Donations from 2 women with high HPV-18 Ab titers were pooled to the HPV-18 candidate IS, later established as the WHO official IS for HPV antibodies. Sera that could potentially be used as candidate IS for other oncogenic HPVs have also been identified.ConclusionsIn the Thai population, seroepidemiology implicated HPV types HPV-16,-31,-52 and -58 as particularly associated with cervical cancer. A well characterized cohort study has allowed sourcing of materials for an IS for HPV-18 antibodies and could conceivably be used for IS for other HPV types as well.