Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia

JAMA. 2001 Dec 26;286(24):3106-14. doi: 10.1001/jama.286.24.3106.


Context: Human papillomavirus (HPV) infection is believed to be the central cause of cervical cancer, although most of the epidemiological evidence has come from retrospective, case-control studies, which do not provide information on the dynamics of cumulative or persistent exposure to HPV infection.

Objective: To assess the risks of cervical neoplasia related to prior persistent HPV infections.

Design and setting: Longitudinal study of the natural history of HPV infection and cervical neoplasia in women residing in the city of São Paulo, Brazil, which was conducted between November 1993 and March 1997 and involved repeated measurements of HPV and lesions with follow-up until June 2000.

Participants: A total of 1611 women with no cytological lesions at enrollment and HPV test results available from the first 2 visits.

Main outcome measure: Cervical specimens taken for Papanicolaou cytology and HPV testing every 4 months in the first year and twice yearly thereafter. Incident cervical cancer precursor lesions ascertained by expert review of all cytology smears.

Results: The incidence rate of squamous intraepithelial lesions (SILs) was 0.73 per 1000 women-months (95% confidence interval [CI], 0.5-0.9) among women free of HPV at the 2 initial visits and 8.68 (95% CI, 2.3-15.1) among women with HPV type 16 or 18 infections persisting over both visits. Relative to those negative for HPV oncogenic types at both initial visits, the relative risk (RR) of incident SIL was 10.19 (95% CI, 5.9-17.6) for persistent infections with any known oncogenic HPV types. The equivalent RR of incident high-grade SIL was 11.67 (95% CI, 4.1-33.3). The RRs of lesions were considerably higher for persistent infections with HPV type 16 or 18.

Conclusion: A strong relationship exists between persistent HPV infections and SIL incidence, particularly for HPV types 16 and 18.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • DNA, Viral / analysis
  • Female
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Multivariate Analysis
  • Papanicolaou Test
  • Papillomaviridae / classification
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / epidemiology
  • Risk Factors
  • Tumor Virus Infections / complications*
  • Tumor Virus Infections / diagnosis
  • Tumor Virus Infections / epidemiology
  • 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