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- Title
p16/ki67 and E6/E7 mRNA Accuracy and Prognostic Value in Triaging HPV DNA-Positive Women.
- Authors
Rossi, Paolo Giorgi; Carozzi, Francesca; Ronco, Guglielmo; Allia, Elena; Bisanzi, Simonetta; Gillio-Tos, Anna; Marco, Laura De; Rizzolo, Raffaella; Gustinucci, Daniela; Mistro, Annarosa Del; Frayle, Helena; Confortini, Massimo; Iossa, Anna; Cesarini, Elena; Bulletti, Simonetta; Passamonti, Basilio; Gori, Silvia; Toniolo, Laura; Barca, Alessandra; Bonvicini, Laura
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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.
- Subjects
CERVICAL intraepithelial neoplasia; PROGNOSIS; PAPILLOMAVIRUSES; MESSENGER RNA; RNA analysis; DNA analysis; PAPILLOMAVIRUS disease diagnosis; PROTEINS; RESEARCH; MEDICAL triage; DNA; CROSS-sectional method; RESEARCH methodology; RNA; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; PAPILLOMAVIRUS diseases; DNA-binding proteins; GENOTYPES; TUMOR markers; CERVIX uteri tumors
- Publication
JNCI: Journal of the National Cancer Institute, 2021, Vol 113, Issue 3, p292
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djaa105