1. p16/ki67 and E6/E7 mRNA Accuracy and Prognostic Value in Triaging HPV DNA-Positive Women.
- Author
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Giorgi Rossi P, Carozzi F, Ronco G, Allia E, Bisanzi S, Gillio-Tos A, De Marco L, Rizzolo R, Gustinucci D, Del Mistro A, Frayle H, Confortini M, Iossa A, Cesarini E, Bulletti S, Passamonti B, Gori S, Toniolo L, Barca A, Bonvicini L, Mancuso P, Venturelli F, and Benevolo M
- Subjects
- Adult, Biomarkers analysis, Cross-Sectional Studies, DNA, Viral analysis, DNA, Viral genetics, DNA-Binding Proteins genetics, Female, Genotype, Human papillomavirus 16 genetics, Human papillomavirus 18 genetics, Humans, Middle Aged, Papillomavirus Infections genetics, Papillomavirus Infections pathology, Papillomavirus Infections virology, Prognosis, RNA, Messenger genetics, Repressor Proteins genetics, Triage, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms virology, Uterine Cervical Dysplasia genetics, Uterine Cervical Dysplasia pathology, Uterine Cervical Dysplasia virology, Cyclin-Dependent Kinase Inhibitor p16 genetics, Ki-67 Antigen genetics, Oncogene Proteins, Viral genetics, Papillomavirus Infections diagnosis, RNA, Messenger analysis, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Dysplasia diagnosis
- Abstract
Background: The study presents cross-sectional accuracy of E6 and E7 (E6/E7) mRNA detection and p16/ki67 dual staining, alone or in combination with cytology and human papillomavirus (HPV)16/18 genotyping, as a triage test in HPV DNA-positive women and their impact on cervical intraepithelial neoplasia (CIN2+) overdiagnosis., Methods: Women aged 25-64 years were recruited. HPV DNA-positive women were triaged with cytology and tested for E6/E7 mRNA and p16/ki67. Cytology positive women were referred to colposcopy, and negatives were randomly assigned to immediate colposcopy or to 1-year HPV retesting. Lesions found within 24 months since recruitment were included. All P values were 2-sided., Results: 40 509 women were recruited, and 3147 (7.8%) tested HPV DNA positive; 174 CIN2+ were found: sensitivity was 61.0% (95% confidence interval [CI] = 53.6 to 68.0), 94.4% (95% CI = 89.1 to 97.3), and 75.2% (95% CI = 68.1 to 81.6) for cytology, E6/E7 mRNA, and p16/ki67, respectively. Immediate referral was 25.6%, 66.8%, and 28.3%, respectively. Overall referral was 65.3%, 78.3%, and 63.3%, respectively. Cytology or p16/ki67, when combined with HPV16/18 typing, reached higher sensitivity with a small impact on referral. Among the 2306 HPV DNA-positive and cytology-negative women, relative CIN2+ detection in those randomly assigned at 1-year retesting vs immediate colposcopy suggests a -28% CIN2+ regression (95% CI = -57% to +20%); regression was higher in E6/E7 mRNA-negatives (Pinteraction = .29). HPV clearance at 1 year in E6/E7 mRNA and in p16/ki67 negative women was about 2 times higher than in positive women (Pinteraction < .001 for both)., Conclusions: p16/ki67 showed good performance as a triage test. E6/E7 mRNA showed the highest sensitivity, at the price of too high a positivity rate to be efficient for triage. However, when negative, it showed a good prognostic value for clearance and CIN2+ regression., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
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