Five-Year Risk of Cervical Precancer With p16/Ki67 Dual-Stain or Cytology Triage in HPV-Positive Women


Key Points

  • Positive baseline p16/Ki-67 dual-stain testing was associated with greater risk of ≥ CIN2 vs abnormal cytology.
  • Negative baseline p16/Ki-67 dual-stain testing was associated with reduced risk of ≥ CIN2 vs normal cytology.

In a study reported in JAMA Oncology, Clarke et al found that triage with p16/Ki-67 dual-stain testing (DS) was associated with better risk stratification for cervical precancer than Papanicolaou cytology testing over 5 years among human papilloma virus (HPV)–positive women.

Study Details

The study involved data from 1,549 HPV-positive women aged ≥ 30 years undergoing routine cervical cancer screening in 2012 with HPV and cytology cotesting in the Kaiser Permanente Northern California health-care system. Follow-up was performed through 2017. Five-year cumulative risk of cervical intraepithelial neoplasia of grade 2 or worse (≥ CIN2) or grade 3 or worse (≥ CIN3) was assessed according to baseline DS and cytology was estimated at yearly intervals. Risks were also analyzed in the context of internal clinical management thresholds for colposcopy referral and a 1-year return interval. Patients had a mean age of 42 years at enrollment.

Risk Stratification

Median follow-up was 3.7 years. Positive baseline DS results were associated with significantly higher cumulative 5-year risk of ≥ CIN2 vs abnormal cytology (31.0% vs 25.0%, P = .03).  Women with negative baseline DS results had significantly lower cumulative 5-year risk of ≥ CIN2 vs women with normal cytology (8.5% vs 12.3%, P = .04). Similar findings were made for cumulative risk of ≥ CIN3 according to baseline results.

Cumulative risks of ≥ CIN2 and ≥ CIN3 in DS-positive women and in women with atypical squamous cells of undetermined significance on cytology at baseline exceeded the internal risk thresholds for colposcopy referral for all 5 years. In women who were DS-negative at baseline, cumulative risks of ≥ CIN2 and ≥ CIN3 remained below the colposcopy referral threshold for up to 5 years and crossed the 1-year return referral threshold at year 3. Cumulative risks of ≥ CIN2 and ≥ CIN3 in women who were negative for intraepithelial lesion or malignancy on cytology crossed the threshold for immediate colposcopy referral after year 4 and the 1-year return risk threshold at year 1.

The investigators concluded, “Triage with p16/Ki-67 DS provides better long-term risk stratification than cytology over 5 years. The low risk of cervical precancer in p16/Ki-67 DS–negative women permits safe extension of follow-up intervals for 3 years.”

The study was supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute.

Megan Clarke, PhD, MHS, of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, is the corresponding author for the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.