No abstract

Purpose Cytology-based screening has limited sensitivity to detect prevalent cervical precancers. HPV DNA testing is highly sensitive and provides a high, long-term reassurance of low risk of cervical cancer. However, the specificity of HPV DNA testing is limited, requiring additional, more disease-specific markers for efficient screening approaches. Experimental Design Liquid based cytology samples were collected from 625 women referred to colposcopy. A slide was stained using the CINtec plus cytology assay. Pap cytology and HPV genotyping were performed from the same vial. Clinical performance characteristics were calculated for all women, stratified by age, and for women referred with an LSIL Pap. Results p16/Ki-67-positivity increased with histological severity, from 26.8% in normal histology, 46.5% in CIN1, 82.8% in CIN2, to 92.8% in CIN3. Among women with CIN3, p16/Ki-67-positivity increased from 77.8% for women <30 years without HPV16 to 100% for women 30 years and older with HPV16. The sensitivity and specificity to detect CIN3+ were 93.2% and 46.1%, respectively, and increased to 97.2% and 60.0% among women 30 years and older. In women with HR-HPV-positive ASC-US and LSIL, sensitivity and specificity for detection of CIN3 were 90.6% and 48.6%, respectively. Conclusions p16/Ki-67 testing could reduce referral to colposcopy by almost half while detecting the most severe cases of CIN3. The high sensitivity of p16/Ki-67 with significantly improved specificity compared to HPV testing makes p16/Ki-67 a viable option for LSIL triage. Further studies are required to evaluate p16/Ki-67 as triage marker in HPV-based screening strategies.

Collection of additional lesion-directed biopsies during colposcopy increased detection of histologic HSIL, regardless of patient characteristics. Taking additional biopsies when multiple lesions are present should become the standard practice of colposcopic biopsy.