Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study

Lancet. 1999 Jul 3;354(9172):20-5. doi: 10.1016/S0140-6736(98)12490-X.


Background: A relation has been established between infection with high-risk types of human papillomavirus and development of cervical cancer. We investigated a role for testing for human papillomavirus as part of cervical-cancer screening.

Methods: We monitored by cytology, colposcopy, and testing for high-risk human papillomavirus 353 women referred to gynaecologists with mild to moderate and severe dyskaryosis. The median follow-up time was 33 months. At the last visit we took biopsy samples. Our primary endpoint was clinical progression, defined as cervical intraepithelial neoplasia (CIN) 3, covering three or more cervical quadrants on colposcopy, or a cervical-smear result of suspected cervical cancer.

Findings: 33 women reached clinical progression. All had persistent infection with high-risk human papillomavirus. The cumulative 6-year incidence of clinical progression among these women was 40% (95% CI 21-59). In women with end histology CIN 3, 98 (95%) of 103 had persistent infection with high-risk human papillomavirus from baseline. Among women with mild to moderate dyskaryosis at baseline, a second test for human papillomavirus at 6 months predicted end histology CIN 3 better than a second cervical smear.

Interpretation: Persistent infection with high-risk human papillomavirus is necessary for development and maintenance of CIN 3. All women with severe dyskaryosis should be referred to gynaecologists, whereas women with mild to moderate dyskaryosis should be referred only after a second positive test for high-risk human papillomavirus at 6 months.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biopsy
  • Cervix Uteri / pathology
  • Colposcopy
  • Female
  • Follow-Up Studies
  • Humans
  • Mass Screening*
  • Middle Aged
  • Neoplasm Staging
  • Papillomaviridae*
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / pathology
  • Precancerous Conditions / diagnosis*
  • Precancerous Conditions / pathology
  • Risk Factors
  • Tumor Virus Infections / diagnosis*
  • Tumor Virus Infections / pathology
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / pathology
  • Vaginal Smears