Management of women who test positive for high-risk types of human papillomavirus: the HART study

Lancet. 2003 Dec 6;362(9399):1871-6. doi: 10.1016/S0140-6736(03)14955-0.


Background: Certain types of human papillomavirus (HPV) are the primary cause of almost all cervical cancers. HPV testing of cervical smears is more sensitive but less specific than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN2+). HPV testing as a primary screening approach requires efficient management of HPV-positive women with negative or borderline cytology. We aimed to compare the detection rate and positive predictive values of HPV assay with cytology and to determine the best management strategy for HPV-positive women.

Methods: We did a multicentre screening study of 11085 women aged 30-60 years. Women with borderline cytology and women positive for high-risk HPV with negative cytology were randomised to immediate colposcopy or to surveillance by repeat HPV testing, cytology, and colposcopy at 12 months.

Findings: HPV testing was more sensitive than borderline or worse cytology (97.1% vs 76.6%, p=0.002) but less specific (93.3% vs 95.8%, p<0.0001) for detecting CIN2+. Of 825 randomised women, surveillance at 12 months was as effective as immediate colposcopy. In women positive for HPV at baseline, who had surveillance, 73 (45%) of 164 women with negative cytology and eight (35%) of 23 women with borderline cytology were HPV negative at 6-12 months. No CIN2+ was found in these women, nor in women with an initial negative HPV test with borderline (n=211) or mild (32) cytology.

Interpretation: HPV testing could be used for primary screening in women older than 30 years, with cytology used to triage HPV-positive women. HPV-positive women with normal or borderline cytology (about 6% of screened women) could be managed by repeat testing after 12 months. This approach could potentially improve detection rates of CIN2+ without increasing the colposcopy referral rate.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Age Factors
  • Colposcopy
  • DNA Probes, HPV
  • DNA, Viral / genetics
  • DNA, Viral / isolation & purification
  • Female
  • Humans
  • Mass Screening
  • Middle Aged
  • Papillomaviridae* / isolation & purification*
  • Sensitivity and Specificity
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / pathology*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology*
  • Vaginal Smears


  • DNA Probes, HPV
  • DNA, Viral