Role of p16 testing in cervical cancer screening among HIV-infected women

• Type of Material: Article
• Authors: Christine J. McGrath, University of Washington; Rochelle Garcia, University of Washington; Trong T. Trinh, University of Washington; Barbra A. Richardson, University of Washington; Grace C. John-Stewart, University of Washington; Evans Nyongesa-Malava, Kenyatta National Hospital; Nelly R. Mugo, Kenyatta National Hospital; Emily H. Glynn, University of Washington; Samah R. Sakr, Coptic Hospital; Hugo De Vuyst, International Agency for Research on Cancer; Michael Chung, Emory University
• Language: English
• Date: 2017-10-12
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2017 McGrath et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0185597
• Title of Journal or Parent Work: PLOS ONE
• Volume: 12
• Issue: 10
• Start Page: e0185597
• End Page: e0185597
• Grant/Funding Information: This work was supported by a grant from the Washington Global Health Alliance [PSP6145] to M.H.C.; the Fondation de France [Nr16673] to H.D.V.; the National Institutes of Health [K23-AI065222-04/AI/NIAID to M.H.C.; T32-AI704438/AI/NIAID to T.T.T; and 1K24HD054314-04/HD/NICHD to G.J-S.]; and the Bill and Melinda Gates Foundation [35537] to M.H.C. The Coptic Hope Center for Infectious Diseases is supported by the PEPFAR through a cooperative agreement [U62/CCU024512-04] from the Centers for Disease Control and Prevention (CDC).
• Keywords: Science & Technology - Other Topics; KI-67; HUMAN-PAPILLOMAVIRUS INFECTION; DIAGNOSIS; EXPRESSION; Science & Technology; P16(INK4A); Multidisciplinary Sciences; LESIONS; CYTOLOGY; INTRAEPITHELIAL NEOPLASIA
• Research Categories: Biology, Virology; Health Sciences, Oncology

Abstract

Background: p16 immunohistochemistry is used to evaluate for HPV-associated cervical intraepithelial neoplasia. The diagnostic performance of p16 in HIV infection is unclear. Methods: Between June-December 2009, HIV-infected women underwent Papanicolaou (Pap) smear, human papillomavirus (HPV) testing, visual inspection with acetic acid (VIA), and colposcopy-directed biopsy as the disease gold standard at a HIV clinic in Kenya. Pap smears were evaluated for p16 expression. Sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC) of p16 to detect CIN2/3 on histology and the impact of immunosuppression and ART was assessed. Results: Of 331 cervical samples with p16 expression, p16 sensitivity and specificity to detect CIN2/3 was 54.1% and 72.4% respectively, which was lower than Pap and HPV in sensitivity, but higher in specificity than Pap, HPV, and VIA. Combining tests and p16 reduced sensitivity and increased specificity of Pap from 90.5% to 48.7% and 51.4% to 81.7%; of VIA from 59.5% to 37.8% and 67.6% to 89.9%; and of HPV from 82.4% to 50.0% and 55.3% to 84.8%. Combination p16 increased the PPV of Pap from 34.9% to 43.4%; of HPV from 34.7% to 48.7%; and VIA from 34.9% to 51.9%. Adjunctive p16 did not change AUC (P>0.05). P16 performance was not altered by immunosuppression or ART use. Combining p16 with HPV and VIA reduced the variation in HPV and VIA performance associated with CD4 and ART. Conclusion: As an adjunctive test in HIV-infected women, p16 immunohistochemistry increased specificity and PPV of HPV and VIA for CIN2/3, and was not altered in performance by immunosuppression, ART, or age.