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

• Published in: BMC cancer Vol. 19; no. 1; pp. 271 - 9
• Main Authors: Zhu, Yuanhang, Ren, Chenchen, Yang, Li, Zhang, Xiaoan, Liu, Ling, Wang, Zhaoxin
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 27.03.2019; BioMed Central; BMC
• Subjects: Accuracy; Adult; Aged; Analysis; ASCUS; Atypical Squamous Cells of the Cervix - metabolism; Atypical Squamous Cells of the Cervix - virology; Biomarkers; Care and treatment; Cellular biology; Cervical cancer; Cervix dysplasia; CIN; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Cytology; Deoxyribonucleic acid; Diagnosis; DNA; DNA, Viral - genetics; Dysplasia; E6/E7; Early Diagnosis; Female; Genetic testing; Histochemistry; HPV; Human papillomavirus; Humans; Immunocytochemistry; Immunohistochemistry; Infections; Ki-67 Antigen - metabolism; Medical screening; Messenger RNA; Middle Aged; mRNA; Oncogene Proteins, Viral - genetics; p16/Ki67; Papillomaviridae - genetics; Papillomaviridae - metabolism; Papillomavirus infections; Papillomavirus Infections - diagnosis; Papillomavirus Infections - metabolism; Papillomavirus Infections - virology; Population; RNA; Sensitivity and Specificity; Stains & staining; Systematic review; Triage; Uterine Cervical Dysplasia - diagnosis; Uterine Cervical Dysplasia - metabolism; Uterine Cervical Dysplasia - virology; Women; Women's health; Womens health; Young Adult; United States > US; China; CIN; mRNA; ASCUS; E6/E7; p16/Ki67; HPV
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-5492-9

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. 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. 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+). p16/Ki67 immunostaining and HPV E6/E7 mRNA testing, especially the former, may be promising tools in triage of ASCUS.