High-risk human papillomavirus (hrHPV) positive women require triage testing to identify those with high-grade cervical intraepithelial neoplasia or cancer (≥CIN3). Although Pap cytology is considered an attractive triage test, its applicability is hampered by its subjective nature. This study prospectively compared the clinical performance of p16/Ki-67 dual stained cytology to that of Pap cytology, with or without HPV16/18 genotyping, in hrHPV-positive women.
Among women visiting gynaecologic outpatient clinics, 446 high-risk HPV-positive women (age 18-66 years) were recruited. From all women, cervical scrapes and colposcopy-directed biopsies were obtained. Cervical scrapes were subjected to Pap cytology, HPV16/18 genotyping and p16/Ki-67-dual stained cytology.
The ≥CIN3 sensitivity of p16/Ki-67 dual-stained cytology (93.8%) did neither differ significantly from that of Pap cytology (87.7%; ratio 1.07, 95% CI:0.97-1.18) nor from that of Pap cytology combined with HPV16/18 genotyping (95.1%; ratio 0.99, 95% CI:0.91-1.07). However, the ≥CIN3 specificity of p16/Ki-67 dual stained cytology (51.2%) was significantly higher than that of Pap cytology (44.9%; ratio 1.14, 95% CI:1.01-1.29) and Pap cytology combined with HPV16/18 genotyping (25.8%; ratio 1.99, 95% CI:1.68-2.35). After exclusion of women who had been referred because of abnormal Pap cytology, the ≥CIN3 specificity of p16/Ki-67 dual stained cytology (56.7%) remained the same, whereas that of Pap cytology (60.3%) increased substantially, resulting in a similar specificity of both assays (ratio 0.94, 95% CI:0.83-1.07) in this sub-cohort.
p16/Ki-67 dual-stained cytology may serve as a more objective alternative to Pap cytology for triage of hrHPV-positive women.