Evidence of Decreased Long-term Risk of Cervical Precancer after Negative Primary HPV Screens Compared with Negative Cytology Screens in a Longitudinal Cohort Study

Cancer Epidemiol Biomarkers Prev. 2024 Jul 1;33(7):904-911. doi: 10.1158/1055-9965.EPI-23-1587.

Abstract

Background: The growing use of primary human papillomavirus (HPV) cervical cancer screening requires determining appropriate screening intervals to avoid overtreatment of transient disease. This study examined the long-term risk of cervical precancer after HPV screening to inform screening interval recommendations.

Methods: This longitudinal cohort study (British Columbia, Canada, 2008 to 2022) recruited women and individuals with a cervix who received 1 to 2 negative HPV screens (HPV1 cohort, N = 5,546; HPV2 cohort, N = 6,624) during a randomized trial and women and individuals with a cervix with 1 to 2 normal cytology results (BCS1 cohort, N = 782,297; BCS2 cohort, N = 673,778) extracted from the provincial screening registry. All participants were followed through the registry for 14 years. Long-term risk of cervical precancer or worse [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)] was compared between HPV and cytology cohorts.

Results: Cumulative risks of CIN2+ were 3.2/1,000 [95% confidence interval (CI), 1.6-4.7] in HPV1 and 2.7/1,000 (95% CI, 1.2-4.2) in HPV2 after 8 years. This was comparable with the risk in the cytology cohorts after 3 years [BCS1: 3.3/1,000 (95% CI, 3.1-3.4); BCS2: 2.5/1,000 (95% CI, 2.4-2.6)]. The cumulative risk of CIN2+ after 10 years was low in the HPV cohorts [HPV1: 4.7/1,000 (95% CI, 2.6-6.7); HPV2: 3.9 (95% CI, 1.1-6.6)].

Conclusions: Risk of CIN2+ 8 years after a negative screen in the HPV cohorts was comparable with risk after 3 years in the cytology cohorts (the benchmark for acceptable risk).

Impact: These findings suggest that primary HPV screening intervals could be extended beyond the current 5-year recommendation, potentially reducing barriers to screening.

MeSH terms

  • Adult
  • British Columbia / epidemiology
  • Cytodiagnosis
  • Early Detection of Cancer* / methods
  • Female
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections* / diagnosis
  • Papillomavirus Infections* / epidemiology
  • Papillomavirus Infections* / virology
  • Precancerous Conditions / diagnosis
  • Precancerous Conditions / epidemiology
  • Precancerous Conditions / pathology
  • Precancerous Conditions / virology
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / epidemiology
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms* / diagnosis
  • Uterine Cervical Neoplasms* / epidemiology
  • Uterine Cervical Neoplasms* / pathology
  • Uterine Cervical Neoplasms* / virology
  • Vaginal Smears / methods