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

J Clin Virol. 2016 May;78:89-92. doi: 10.1016/j.jcv.2016.03.014. Epub 2016 Mar 16.


Background: HPV serology is important for studies of vaccine immunogenicity, but can not be performed in a comparable manner without international standardisation.

Objectives: To 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 design: 946 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.

Results: Seroprevalences 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.

Conclusions: In 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.

Keywords: Cervical cancer; Human papillomavirus (HPV); International standard serum; Luminex; Serology; Thailand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral / blood*
  • Cohort Studies
  • Female
  • Human papillomavirus 18 / immunology*
  • Humans
  • Immunoassay / standards*
  • Middle Aged
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / immunology*
  • Reference Standards*
  • Seroepidemiologic Studies
  • Thailand / epidemiology
  • Young Adult


  • Antibodies, Viral