Natural history of progression of HPV infection to cervical lesion or clearance: analysis of the control arm of the large, randomised PATRICIA study

PLoS One. 2013 Nov 19;8(11):e79260. doi: 10.1371/journal.pone.0079260. eCollection 2013.

Abstract

Background: The control arm of PATRICIA (PApilloma TRIal against Cancer In young Adults, NCT00122681) was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN) or clearance of infection, and associated determinants.

Methods and findings: Women aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI) was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ≥2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+) associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 women with 6902 6MPIs). Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65), 9.65 (5.97-15.60), 5.68 (3.50-9.21), 5.38 (2.87-10.06) and 3.87 (2.38-6.30) for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear.

Conclusions: Cervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alphapapillomavirus*
  • Cervix Uteri / metabolism
  • Cervix Uteri / pathology
  • Cervix Uteri / virology*
  • Double-Blind Method
  • Female
  • Humans
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / pathology
  • Risk Factors
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*

Associated data

  • ClinicalTrials.gov/NCT00122681

Grants and funding

The study (NCT00122681) was funded by GlaxoSmithKline Biologicals SA, who designed the trial in collaboration with investigators. The costs related to the collection of data from this study, together with the development of this manuscript, were funded and coordinated by GlaxoSmithKline Biologicals SA. All authors contributed to the development of the manuscript and approved the manuscript for publication. The corresponding author (UJ) and the core writing team (UJ, XC, SMG, MRDRR, PN, JP (Johanna Palmroth), LB, DR) had the final responsibility for the decision to submit for publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.