title: Evaluation of p16 immunostaining to predict high-grade cervical intraepithelial neoplasia in women with Pap results of atypical squamous cells of undetermined significance.
abstract: p16 immunostaining has been examined to detect high-grade cervical intraepithelial neoplasia grade (CIN2+) in Pap cytology specimens. However, the utility of p16 in predicting CIN2+ in Pap specimens with atypical squamous cells of undetermined significance (ASC-US) or atypical squamous cells, cannot exclude high-grade squamous intraepithelial neoplasm (ASC-H), is controversial. In this study, we evaluated the utility of p16 immunostaining for predicting CIN2+ in 78 Pap specimens with ASC-US/ASC-H and compared the results in high-risk HPV DNA and the follow-up biopsies. p16 immunostaining was positive in 47% (37/78) of the Pap specimens. Of the 13 Pap specimens with follow-up biopsy results of CIN2+, 7 (54%) were positive for p16. p16 positivity in the Pap specimens was not significantly associated with a CIN2+ biopsy result (P = 0.76). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of p16 immunostaining for predicting CIN2+ were 54%, 52%, 19%, and 85%, respectively. High-risk HPV DNA was detected in 40% (31/78) of the Pap specimens. The sensitivity, specificity, PPV, and NPV of HPV DNA for predicting CIN2+ were 100%, 72%, 42%, and 100%, respectively. High-risk HPV genotypes were detected in six p16-negative specimens with follow-up biopsy results of CIN2+. Our findings suggest that the utility of p16 immunostaining for predicting CIN2+ in Pap specimens with ASC-US/ASC-H is limited. Scant abnormal cells in Pap specimens with ASC-US/ASC-H may have contributed to the low p16 sensitivity.
authors.affiliation: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4009, USA. mguo@mdanderson.org
authors.forename: Ming
authors.initials: M
authors.lastname: Guo
authors.forename: Irfan
authors.initials: I
authors.lastname: Warriage
authors.forename: Bramara
authors.initials: B
authors.lastname: Mutyala
authors.forename: Shobha
authors.initials: S
authors.lastname: Patel
authors.forename: E
authors.initials: E
authors.lastname: Lin
authors.forename: Yun
authors.initials: Y
authors.lastname: Gong
authors.forename: Nour
authors.initials: N
authors.lastname: Sneige
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D005838:Genotype; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D011237:Predictive Value of Tests; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins