Human Papillomavirus Assays and Cytology in Primary Cervical Screening of Women Aged 30 Years and Above

PLoS One. 2016 Jan 20;11(1):e0147326. doi: 10.1371/journal.pone.0147326. eCollection 2016.


In women aged ≥ 30 years, Human Papillomavirus testing will replace cytology for primary cervical screening. We compared Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA HPV assays with cytology on 2869 SurePath samples from women undergoing routine screening at 30-65 years in Copenhagen, Denmark. Women with cytological abnormalities were managed according to routine recommendations, with 92% completeness. Those with cytology-normal/HPV-positive samples (on any of the four assays) were invited for repeated cytology and HPV testing in 1.5 year, and 58% had additional testing. HPV testing detected more ≥ CIN3 than cytology (HC2: 35, cobas, CLART: 37, APTIMA: 34, cytology: 31), although statistically the differences were not significant. Cobas and CLART detected significantly more ≥ CIN2 than cytology (cobas, CLART: 49, cytology: 39). The proportion of women with false-positive test results (positive test results without ≥ CIN3) varied between 3.3% with cytology and 14.9% with cobas. All HPV assays led to significantly more false-positive tests, whereas compared to HC2 cobas and CLART were associated with a significantly higher and APTIMA with a significantly lower proportion. Detection of CIN1 was particularly increased for the three DNA assays. With APTIMA combined with cytological triage, about 20% more women were referred for colposcopy than with cytology screening. With the three DNA assays, the increase was ≥ 50%. The number of women with repeated testing was twice as high with APTIMA and almost five times as high with cobas compared to cytology. To our knowledge, Horizon was the only study set in routine practice that compared more than two HPV assays in the same women while also ascertaining the histological status of women with normal cytology/HPV-positive test results. HPV-based screening of Danish women aged 30-65 detected more high-grade CIN but decreased the screening specificity, and increased the demand for additional testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biological Assay / methods*
  • Colposcopy
  • Cytodiagnosis*
  • DNA, Viral / genetics
  • Denmark / epidemiology
  • Early Detection of Cancer
  • Female
  • Humans
  • Middle Aged
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / virology
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / epidemiology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears


  • DNA, Viral

Grants and funding

Genomica, the manufacturer of the CLART HPV2 Assay; Hologic, 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. MR and SP were funded by the Danish Strategic Research Council (grant number: 10-092793). 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.