Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial

BMJ. 2014 Jan 16;348:g130. doi: 10.1136/bmj.g130.

Abstract

Objectives: To assess whether the increased sensitivity of screening for human papillomavirus (HPV) may represent overdiagnosis and to compare the long term duration of protective effect against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HPV based and cytology based screening.

Design: 13 year follow-up of the Swedescreen randomised controlled trial of primary HPV screening.

Setting: Organised cervical screening programme in Sweden.

Participants: 12,527 women aged 32-38 attending organised screening were enrolled and randomised to HPV and cytology double testing (intervention arm, n=6257) or to cytology only, with samples frozen for future HPV testing (control arm, n=6270).

Main outcome measures: Cumulative incidence of CIN2+ and CIN3+ (Kaplan Meier curves). Longitudinal test characteristics were calculated for cytology only, HPV testing only, and cytology and HPV testing combined, adjusting for censoring.

Results: The increased detection of CIN2+ in the intervention arm decreased over time. After six years, the cumulative incidence of CIN3+ was similar in both trial arms, and after 11 years the cumulative incidence of CIN2+ became similar in both arms. The longitudinal sensitivity of cytology for CIN2+ in the control arm at three years was similar to the sensitivity of HPV testing in the intervention arm at five years of follow-up: 85.94% (95% confidence interval 76.85% to 91.84%) v 86.40% (79.21% to 91.37%). The sensitivity of HPV screening for CIN3+after five years was 89.34% (80.10% to 94.58%) and for cytology after three years was 92.02% (80.59% to 96.97%).

Conclusions: Over long term follow-up, the cumulative incidence of CIN2+ was the same for HPV screening and for cytology, implying that the increased sensitivity of HPV screening for CIN2+ reflects earlier detection rather than overdiagnosis. The low long term risks of CIN3+ among women who tested negative in HPV screening, support screening intervals of five years for such women.

Trial registration: Clinicaltrials.gov NCT00479375.

Publication types

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

MeSH terms

  • Adult
  • Cervical Intraepithelial Neoplasia / diagnosis*
  • Cervical Intraepithelial Neoplasia / epidemiology
  • Cervical Intraepithelial Neoplasia / virology
  • DNA, Viral / analysis*
  • Diagnosis, Differential
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Mass Screening / methods*
  • Middle Aged
  • Neoplasm Staging
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / virology
  • Reproducibility of Results
  • Retrospective Studies
  • Sweden / epidemiology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears / methods*
  • Young Adult

Substances

  • DNA, Viral

Associated data

  • ClinicalTrials.gov/NCT00479375