Good performance of p16/Ki‐67 dual‐stain cytology for detection and post‐treatment surveillance of high‐grade CIN/VAIN in a prospective, cross‐sectional study

Abstract

Background The limited sensitivity of Papanicolaou (Pap) cytology and the low specificity of HPV testing in detecting cervical or vaginal lesions means that either precancers are missed or women without lesions are overtreated. To improve performance outcomes, p16/Ki‐67 dual‐stain cytology has been introduced as a useful biomarker. Methods A prospective, cross‐sectional study was performed and included 599 patients. Clinical performance estimates of Pap cytology, HPV DNA assay, and p16/Ki‐67 dual‐stain cytology for the detection of CIN2+/VAIN2+ were determined and compared. Results The sensitivity and specificity of p16/Ki‐67 dual‐stain cytology in detecting histology proven CIN2+/VAIN2+ was 91.6% and 95.0%, respectively, while that of Pap cytology was 42.1% and 95.2%, respectively, and that of HPV DNA testing was 100% and 41.6%, respectively. Among the three tests, the AUC of p16/Ki‐67 immunocytochemistry was the largest, both for detecting cervical lesions and vaginal lesions, at 0.932 and 0.966, respectively. Among women who were HPV 16/18 positive or 12‐other hrHPV positive and Pap positive (≥ASCUS), dual staining reduced the number of unnecessary colposcopy referrals from 274 to 181. Among the women who were 12‐other hrHPV positive and Pap negative, dual staining could prevent underdiagnosis in six patients with CIN2+/VAIN2+ when used as a triage marker. Dual staining also identified four women with high‐grade lesions detected by diagnostic conization but with negative colposcopy‐guided biopsy results. Conclusion p16/Ki‐67 dual staining may be a promising tool for predicting high‐grade cervical and vaginal lesions.

Role of Dual-Staining p16/Ki-67 in the Management of Patients under 30 Years with ASC-US/L-SIL

“…Currently, post-treatment monitoring of patients with CIN is performed by cytology or co-testing (cytology and HR-HPV) [ 59 ]. Given the risk of recurrent CIN2 or worse (rCIN2+), dual-staining has been proposed for the surveillance of these patients [ 60 , 61 ].…”

An Adsorptive and Antioxidant Vaginal Gel Clears High-Risk HPV- and p16/Ki-67-Associated Abnormal Cytological Cervical Findings: A post-hoc Subgroup Analysis of a Prospective Randomized Controlled Trial on CIN2 and p16 Positive CIN1

“…In another study specificity for both p16/Ki-67 alone and for cytology was 95%, and for HPV alone it was 41.6% for detecting CIN2+/VAIN2+. Additionally, p16/Ki-67 was the best test for detecting cervical and vaginal lesions and to prevent under-diagnoses ( 18 ). In a study with ASC-US patients, the specificity of detecting high-grade dysplasia was highest for p16/Ki-67 immunocytochemistry, 74.2% in CIN3+ and 82.5% in CIN2+; significantly better than for HPV ( 19 ).…”

“…That study demonstrated efficacy and safety of this particular vaginal gel (14). Most patients were also tested for p16/Ki-67 in cervical smears, recognized for greater specificity than both cytology and HPV (14,(17)(18)(19)(20)(21). The presented post-hoc analysis was limited to those patients (172 of 216 in the parent trial) who had a positive p16/Ki-67 test at study entry.…”

Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance

“…Post-treatment monitoring by CADM1/MAL-methylation analysis identified women with an increased risk of recurrent CIN2/3 [13]. Moreover, a significant increase in specificity for recurrent disease was observed for hrHPV/p16/Ki67/co-testing in comparison to hrHPV/cytology co-testing [14,15].…”