Performance of p16/Ki67 immunostaining, HPV E6/E7 mRNA testing, and HPV DNA assay to detect high-grade cervical dysplasia in women with ASCUS

BACKGROUND: Atypical squamous cell of undetermined significance (ASCUS) is a common cervical cytological diagnosis. At present, HPV DNA assay is used to triage these patients, but its lower specificity brings a series of problems. The purpose of this study was to evaluated the value of p16/Ki67 immunostaining, HPV E6/E7 mRNA testing in triaging women with ASCUS by comparing HPV DNA assay. METHODS: Liquid based cytology specimens were collected from 300 patients. P16/Ki67 immunocytochemistry using the CINtec® Plus Kit and HPV E6/E7 mRNA testing by QuantiVirus®HPV E6/E7 mRNA assay used the same cytology sample. Detection rates of each test were evaluated against histopathology. RESULTS: All assays yielded a high sensitivity for the detection of CIN3+ (100% (86.7–100) for HPV DNA assay, 88.0% (70.0–95.8) for HPV E6/E7 mRNA testing and 100% (86.7–100) for p16/Ki67 immunocytochemistry) and CIN2+ (98.2% (90.2–99.7) for HPV DNA assay, 87.0% (75.6–93.6) for HPV E6/E7 mRNA testing, 98.2% (90.2–99.7) for p16/Ki67 immunocytochemistry). The specificity to detect high grade dysplasia was highest for p16/Ki67 immunocytochemistry (74.2% (68.7–79.0) in CIN3+ and 82.5% (77.3–86.8) in CIN2+), followed by HPV E6/E7 mRNA testing (39.6% (34.0–45.5) in CIN3+ and 42.7% (36.7–48.9) in CIN2+) and HPV DNA assay (16.0% (12.1–20.8) in CIN3+ and 17.5% (13.2–22.7) in CIN2+). CONCLUSIONS: p16/Ki67 immunostaining and HPV E6/E7 mRNA testing, especially the former, may be promising tools in triage of ASCUS.