title: The Accuracy of p16/Ki-67 and HPV Test in the Detection of CIN2/3 in Women Diagnosed with ASC-US or LSIL.
abstract: The objective of this study was to compare the accuracies of double staining for p16/Ki-67 and the molecular test for high-risk HPV (hr-HPV) to identify high-grade cervical intraepithelial neoplasia (CIN2/CIN3) in women with cervical cytology of atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Data were collected from 201 women who underwent cervical cytology screening in the Barretos Cancer Hospital and their results were categorized as ASC-US (n=96) or LSIL (n=105). All patients underwent colposcopy with or without cervical biopsy for diagnosis of CIN2/CIN3. The hr-HPV test (Cobas 4800 test) and immunocytochemistry were performed to detect biomarkers p16/Ki-67 (CINtec PLUS test). Two samples (1 ASC-US/1 LSIL) were excluded from the analysis due to inconclusive results of the histologic examination. There were 8 cases of CIN2/CIN3 among 95 women with ASC-US (8.4%), and 23 cases of CIN2/CIN3 among 104 women with LSIL (22.1%). In the group of women with ASC-US, the sensitivity and specificity in diagnosing CIN2/CIN3 were 87.5% and 79.5% for the HPV test and 62.5% and 93.1% for p16/Ki-67. Among women with LSIL, the sensitivity and specificity in the diagnosis of CIN2/CIN3 were 87% and 34.7% for the HPV test and 69.6% and 75.3% for immunocytochemistry. Superior performance was observed for p16/Ki-67 double staining, especially among women under 30 for whom the test had an area under the ROC curve of 0.762 (p<0.001). Both p16/Ki-67 double staining and the hr-HPV DNA test had similar performance in predicting high-grade cervical intraepithelial neoplasia among women with ASC-US. The best performance was observed in women aged >30 years. In younger women (≤30 years) with LSIL, p16/Ki-67 had greater accuracy in identifying precursor lesions. Among women >30 years diagnosed with LSIL, the two methods showed similar performance.
authors.affiliation: Cancer Prevention Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Júlio C
authors.initials: JC
authors.lastname: Possati-Resende
authors.affiliation: Teaching and Research Institute, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: José H T G
authors.initials: JH
authors.lastname: Fregnani
authors.affiliation: Pathology Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Ligia M
authors.initials: LM
authors.lastname: Kerr
authors.affiliation: Cancer Prevention Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Edmundo C
authors.initials: EC
authors.lastname: Mauad
authors.affiliation: Molecular Oncology Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Laboratory of Medical Investigation (LIM-14), School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Adhemar
authors.initials: A
authors.lastname: Longatto-Filho
authors.affiliation: Pathology Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Molecular Oncology Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Cristovam
authors.initials: C
authors.lastname: Scapulatempo-Neto
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology / Q000821:virology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D019394:Ki-67 Antigen