Minor Cytological Abnormalities and up to 7-Year Risk for Subsequent High-Grade Lesions by HPV Type

PLoS One. 2015 Jun 17;10(6):e0127444. doi: 10.1371/journal.pone.0127444. eCollection 2015.

Abstract

Objective: Diagnoses of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are common, but the corresponding risk of disease varies by human papillomavirus (HPV) status, complicating management strategies. Our aim was to estimate the longer-term risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with ASCUS/LSIL by age, HPV status, and genotype(s).

Methods: A total of 314 women with ASCUS/ LSIL were followed for a median of 3.8 years. Baseline HPV status was determined by reflex testing and women with histologically confirmed CIN2+ were identified through linkage to the Swedish National Quality Register for Cervical Cancer Prevention. Cumulative incidence and hazard ratios were estimated to explore differences between index data and associations with CIN2+.

Results: In total, 89 women (28.3%) developed CIN2+. High-risk (HR) HPV-positive women developed significantly more CIN2+ than HR-HPV-negative women (cumulative incidence 3.5 years after the index test: 42.2%, 95% CI: 32.5-53.5 for HPV16/18; 36.2%, 95% CI: 28.3-45.4 for other HR-HPV types; and 2.0%, 95% CI: 0.5-7.8 for HR-HPV-negative women; p<0.0001).

Conclusion: HPV status was of greatest importance in determining the risk of CIN2+. The risk was low among HPV-negative women during the first years of follow-up, suggesting these women could be followed less intensively. HPV16/18-positive women may need intensified follow-up as they showed the highest risk of CIN2+.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atypical Squamous Cells of the Cervix / pathology
  • Atypical Squamous Cells of the Cervix / virology
  • DNA, Viral / genetics*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Genotype
  • Human papillomavirus 16 / classification
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / pathogenicity*
  • Human papillomavirus 18 / classification
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / pathogenicity*
  • Humans
  • Middle Aged
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Risk Assessment
  • Squamous Intraepithelial Lesions of the Cervix / diagnosis*
  • Squamous Intraepithelial Lesions of the Cervix / pathology
  • Squamous Intraepithelial Lesions of the Cervix / virology
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • DNA, Viral

Grants and funding

This research was supported by the Swedish Cancer Foundation (070623, CAN 2007/1044, 11 0544, CAN 2011/471), URL: www.cancerfonden.se, SA; Karolinska Institutet Cancer Strategic Grants (5888/05-722), URL: www.ki.se, SA; Swedish Research Council (521-2008-2899), URL: www.vr.se, SA; Stockholm County Council (20130097) URL: www.skl.se, SA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.