The use of p16/Ki-67 dual staining technology on cervical cytology of patients undergoing a LLETZ procedure.

Objectives: The main objective of this prospective observational study was to investigate the diagnostic performance of the p16/Ki-67 dual stain technique (DST) for detecting CIN 2+ in a LLETZ referral setting. Test performances were compared with HR-HPV testing and Pap cytology.

Methods: All patients referred for a LLETZ procedure were candidates for participation in this trial. A total of 110 patients were enrolled between October 2016 and March 2017. From each participant, a cervical cytology sample was obtained before the onset of the LLETZ procedure. On each sample, the dual stain technique (Roche CINtec PLUS ® test), Pap cytology and an HPV DNA assay (identifying 17 different HPV types) were performed.

Results: The overall disease prevalence of CIN 2+ was 56%. The mean age was 41 years, with 38% of patients being younger than 35 years. The overall sensitivity and specificity of the dual stain technique for detecting CIN 2+ was 94% (95% CI: 84.30-98.21%) and 58% (95% CI: 43.21-72.93%) respectively with a PPV of 74% (95% CI: 67.34-80.31%) and a NPV of 88% (95% CI: 72.48-94.90%). HR-HPV testing results in a similar sensitivity of 92% (95% CI: 82.17-97.33%) but considerable lower specificity of 21% (95% CI: 11.17-33.35%) compared to the dual stain technique. At an ASCUS or worse threshold, Pap cytology had the lowest sensitivity of 89% (95% CI 78.11-95.34%) compared to dual staining and HR-HPV testing. Specificity was better (48% with 95% CI of 33.29-62.81%) than that of HR-HPV testing but not as good as the DST.

Conclusion: p16/Ki-67 dual staining provides high sensitivity and improved specificity compared to HR-HPV testing and Pap cytology for detecting CIN 2+, making it an interesting tool for identifying relevant disease in patients referred for a LLETZ procedure.