Persistence and load of high-risk HPV are predictors for development of high-grade cervical lesions: a longitudinal French cohort study

Int J Cancer. 2003 Sep 1;106(3):396-403. doi: 10.1002/ijc.11222.


Oncogenic HPV types are the major cause of worldwide cervical cancer, but only a small proportion of infected women will develop high-grade cervical intraepithelial neoplasia or cancer (CIN2/3+). We performed a prospective study including 781 women with normal, atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LGSIL) cytology, and infected or not by high-risk (HR) HPV tested by Hybrid Capture II. Women were followed up every 6 months for a median period of 22 months. Among the HR-HPV-positive women at entry, more than half cleared their virus in 7.5 months; the clearance rate was greater for low viral loads than for high loads and also was higher in women with an initial ASCUS/LGSIL smear than in women with normal cytology. The incidence of cytologic abnormalities strongly depended on baseline viral load and HR-HPV persistence. Maintenance of cytologic abnormalities was associated with the outcome of HR-HPV status (negative<transient<persistent) but not with baseline load. Progression to CIN2/3+ was achieved only in women with persistent HR-HPV infection. The risk of CIN2/3+ also was increased with initial high loads (> or =100 pg/mL). Conversely, women who were consistently HR-HPV negative or transiently HR-HPV positive, whatever the cytology at baseline was, did not develop CIN2/3+ during follow-up. Age seemed to affect only the rate of incident HR-HPV infection. In conclusion, our data suggest that women repeatedly tested positive for HR-HPV are at risk of developing CIN2/3+, even when initial cytology is normal. A high viral load could be used as a short-term marker of progression toward precancerous lesions, although lower load does not inevitably exclude progressive disease.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology*
  • Cervical Intraepithelial Neoplasia / epidemiology
  • Cervical Intraepithelial Neoplasia / pathology
  • Cervical Intraepithelial Neoplasia / virology*
  • Cervix Uteri / cytology
  • Cohort Studies
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • False Negative Reactions
  • False Positive Reactions
  • Female
  • France / epidemiology
  • Humans
  • Incidence
  • Longitudinal Studies
  • Middle Aged
  • Papillomaviridae / physiology*
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology*
  • Prospective Studies
  • Risk Factors
  • Tumor Virus Infections / epidemiology
  • Tumor Virus Infections / pathology
  • Tumor Virus Infections / virology*
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*
  • Vaginal Smears
  • Viral Load


  • DNA, Viral