Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study

Int J Cancer. 2016 May 15;138(10):2428-38. doi: 10.1002/ijc.29971.


The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan-Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6-month persistent infection (6MPI) or infection of any duration. The 4-year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non-oncogenic types. For 6MPI, the highest risk was associated with HPV-33 (hazard ratio [HR]: 31.9 [8.3-122.2, p < 0.0001]). The next highest risk was with HPV-16 (21.1 [6.3-70.0], p < 0.0001). Similar findings were seen for infections of any duration. Significant risk was also observed for HPV-18, HPV-31, and HPV-45. Concomitant HPV infection or CIN grade 1 or greater associated with a different oncogenic HPV type increased risk. Most women (79.3%) with an HPV infection at baseline cleared detectable infections of any duration, and 69.9% cleared a 6MPI. The risk of progression of HPV infection to CIN2+ in women >25 years in this study was similar to that in women 15-25 years in PATRICIA.

Keywords: CIN; HPV; VIVIANE; adult women; natural history.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alphapapillomavirus / classification
  • Clinical Trials, Phase III as Topic
  • Disease Progression
  • Early Detection of Cancer
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / prevention & control
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / immunology
  • Public Health Surveillance
  • Risk
  • Uterine Cervical Dysplasia / epidemiology
  • Uterine Cervical Dysplasia / etiology
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / etiology*
  • Uterine Cervical Neoplasms / pathology*


  • Papillomavirus Vaccines

Associated data