Disagreement between human papillomavirus assays: an unexpected challenge for the choice of an assay in primary cervical screening

PLoS One. 2014 Jan 20;9(1):e86835. doi: 10.1371/journal.pone.0086835. eCollection 2014.

Abstract

We aimed to determine the disagreement in primary cervical screening between four human papillomavirus assays: Hybrid Capture 2, cobas, CLART, and APTIMA. Material from 5,064 SurePath samples of women participating in routine cervical screening in Copenhagen, Denmark, was tested with the four assays. Positive agreement between the assays was measured as the conditional probability that the results of all compared assays were positive given that at least one assay returned a positive result. Of all 5,064 samples, 1,679 (33.2%) tested positive on at least one of the assays. Among these, 41% tested positive on all four. Agreement was lower in women aged ≥ 30 years (30%, vs. 49% at <30 years), in primary screening samples (29%, vs. 38% in follow-up samples), and in women with concurrent normal cytology (22%, vs. 68% with abnormal cytology). Among primary screening samples from women aged 30-65 years (n = 2,881), 23% tested positive on at least one assay, and 42 to 58% of these showed positive agreement on any compared pair of the assays. While 4% of primary screening samples showed abnormal cytology, 6 to 10% were discordant on any pair of assays. A literature review corroborated our findings of considerable disagreement between human papillomavirus assays. This suggested that the extent of disagreement in primary screening is neither population- nor storage media-specific, leaving assay design differences as the most probable cause. The substantially different selection of women testing positive on the various human papillomavirus assays represents an unexpected challenge for the choice of an assay in primary cervical screening, and for follow up of in particular HPV positive/cytology normal women.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biological Assay / methods*
  • Denmark
  • Early Detection of Cancer / methods*
  • Female
  • Humans
  • Mass Screening / methods*
  • Middle Aged
  • Papillomaviridae / chemistry*
  • Papillomavirus Infections / diagnosis*
  • Young Adult

Grants and funding

Genomica, the manufacturer of the CLART HPV2 Assay; Hologic/Gen-Probe, the manufacturer of the APTIMA HPV Assay; Roche, the manufacturer of the cobas HPV Test; and Qiagen, the manufacturer of the Hybrid Capture 2 Assay, provided tests, instrumentation, and limited co-funding for laboratory material. According to the contract between the manufacturers, Hvidovre University Hospital, and University of Copenhagen, all four manufacturers had the right to comment on a draft version of this manuscript, but had no editorial rights. MR and SP were funded by the Danish Strategic Research Council (grant number: 10-092793; URL:http://fivu.dk/en/research-and-innovation/councils-and-commissions/the-danishcouncil-for-strategic-research). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The researchers worked independently of the funders.