BACKGROUND AND PURPOSE:

• HPV16 and 18 tests can’t determine who has a transient infection vs precancerous lesion
• Pap cytologic testing is limited by variable sensitivity
• A triage method to evaluate which HPV-positive women should receive further work-up is still needed
• A previous study using a p16 (tumor suppressor protein marker)/Ki-67 (cellular proliferation protein marker) dual stain cytology method showed good sensitivity and specificity compared to cytologic triage alone for women who are HPV-positive
• Wentzensen et al. (JAMA Internal Medicine, 2019) evaluated the performance of a p16/Ki-67 dual stain in combination with HPV16/18 genotyping to triage women who are HPV-positive

METHODS:

• Prospective observational study
• Participants
  • HPV-positive women undergoing HPV and Pap cytological testing with a dual stain result
• Exposures: Triage for HPV-positive result using 16/18 genotyping plus
  • Pap cytology vs
  • Dual staining
• Primary outcomes
  • CIN2+ and CIN3+ within 3 years after sample collection

RESULTS:

• 3,225 women participated
  • Mean (SD) age: 37.9 (11.3) years
• Women with dual stain had a higher risk for CIN3+ than Pap (P = .005)
  • Dual stain: 12.0% (95% CI, 10.5%-13.5%)
  • Pap: 10.3% (95% CI, 9.0%-11.6%)
• Dual stain showed superior risk stratification for CIN3+ vs Pap (regardless of 16 or 18 genotyping result)
• HPV16/18-negative women and negative dual screening had low risk
  • low risk and therefore retesting intervals could be extended to 3 years
• Dual stain triage resulted in
  • Fewer colposcopies (32.1% reduction) per detection of CIN3+ vs Pap
• Results for CIN2+ were similar to those for CIN3+
• Subset of women undergoing routine screening
  • Primary HPV with dual stain showed improved performance compared with Pap including cotesting

CONCLUSION:

• DS was better than Papcytologic testing for the triage of HPV-positive women
  • Equal immediate detection of precancerous lesions
  • Fewer colposcopies with dual stain cytology
• Dual cytology can safely replace Pap testing for triage for HPV screening
• In HPV16/18-negative women with negative DS results, retesting intervals can be extended to 3 years

Learn More – Primary Sources:

Clinical Evaluation of Human Papillomavirus Screening With p16/Ki-67 Dual Stain Triage in a Large Organized Cervical Cancer Screening Program