Adjunctive role of p16/Ki-67 dual-stain cytology in colposcopy referral pathways for cervical precancer and persistent high-risk HPV infection.
This study aimed to evaluate the adjunctive triage performance of p16/Ki-67 dual staining (DS) cytology for cervical lesions in a colposcopy-referred cohort, to analyze its correlation with lesion severity, and to explore its predictive value for persistent high-risk human papillomavirus (HR-HPV) infection.
A total of 109 patients undergoing colposcopic cervical biopsy (recruited via standard HPV+TCT referral criteria) were included. We evaluated the incremental diagnostic performance of adding p16/Ki-67 dual-stain (DS) triage to the standard HPV+TCT referral workflow for detection of CIN2+ and CIN3 +. Among 66 HR-HPV-positive patients with CIN1 or lower lesions, p16/Ki-67 DS cytology was performed, and the patients were followed up for 6 months to assess the predictive value for persistent infection.
The positivity rate of p16/Ki-67 DS cytology gradually increased with the progression of cervical lesion severity (P<0.001). Further triage with p16/Ki-67 DS on the basis of combined HPV+TCT cervical cancer screening yielded sensitivity, specificity, accuracy and AUC of 77.8%, 88.6%, 84.4% and 0.822 ± 0.052 (95%CI: 0.721-0.923) for the diagnosis of CIN2+, and 93.3%, 81.3%, 81.7% and 0.823 ± 0.056 (95%CI: 0.713-0.933) for CIN3+, respectively. Among HR-HPV-positive CIN1/lower lesions, 87.1% of DS-positive patients had persistent infection compared to 62.9% of DS-negative patients (P = 0.025), with an odds ratio of 4.515 (P = 0.028).
In this colposcopy-referred cohort defined by HPV and/or TCT-based referral criteria, p16/Ki-67 dual-stain (DS) cytology exhibited satisfactory adjunctive triage efficacy for identifying CIN2+ and CIN3+, and independently predicted persistent HR-HPV infection among patients with ≤CIN1 lesions. Notably, all analyses in this study are limited to diagnostic efficacy in this referral cohort; any potential clinical applications, including possible reductions in unnecessary procedures, remain exploratory hypotheses that require prospective clinical validation.
A total of 109 patients undergoing colposcopic cervical biopsy (recruited via standard HPV+TCT referral criteria) were included. We evaluated the incremental diagnostic performance of adding p16/Ki-67 dual-stain (DS) triage to the standard HPV+TCT referral workflow for detection of CIN2+ and CIN3 +. Among 66 HR-HPV-positive patients with CIN1 or lower lesions, p16/Ki-67 DS cytology was performed, and the patients were followed up for 6 months to assess the predictive value for persistent infection.
The positivity rate of p16/Ki-67 DS cytology gradually increased with the progression of cervical lesion severity (P<0.001). Further triage with p16/Ki-67 DS on the basis of combined HPV+TCT cervical cancer screening yielded sensitivity, specificity, accuracy and AUC of 77.8%, 88.6%, 84.4% and 0.822 ± 0.052 (95%CI: 0.721-0.923) for the diagnosis of CIN2+, and 93.3%, 81.3%, 81.7% and 0.823 ± 0.056 (95%CI: 0.713-0.933) for CIN3+, respectively. Among HR-HPV-positive CIN1/lower lesions, 87.1% of DS-positive patients had persistent infection compared to 62.9% of DS-negative patients (P = 0.025), with an odds ratio of 4.515 (P = 0.028).
In this colposcopy-referred cohort defined by HPV and/or TCT-based referral criteria, p16/Ki-67 dual-stain (DS) cytology exhibited satisfactory adjunctive triage efficacy for identifying CIN2+ and CIN3+, and independently predicted persistent HR-HPV infection among patients with ≤CIN1 lesions. Notably, all analyses in this study are limited to diagnostic efficacy in this referral cohort; any potential clinical applications, including possible reductions in unnecessary procedures, remain exploratory hypotheses that require prospective clinical validation.