Background: The study presents cross-sectional accuracy of E6/E7 mRNA detection and p16/ki67 dual staining, alone or in combination with cytology and HPV16/18 genotyping, as triage test in HPV DNA-positive women and their impact on CIN2+ overdiagnosis. Methods: Women aged 25-64 were recruited. HPV DNA-positives were triaged with cytology and tested for E6/E7 mRNA and p16/ki67. Cytology positives were referred to colposcopy, while negatives were randomised to immediate colposcopy or to one-year HPV retesting. Lesions found within 24 months since recruitment were included. All p-values were two-sided. Results: 40,509 women were recruited and 3147 (7.8%) tested HPV DNA-positive; 174 CIN2+ were found: sensitivity was 61.0% (95% 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%. 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/cytology-negative women, relative CIN2+ detection in those randomized 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 negatives was about 2 times higher than in positive women (Pinteraction < .001 for both). Conclusions: p16/ki67 showed good performance as 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.

p16/ki67 and E6/E7 mRNA accuracy and prognostic value in triaging HPV DNA-positive women / Rossi, Paolo Giorgi; Carozzi, Francesca; Ronco, Guglielmo; Allia, Elena; Bisanzi, Simonetta; Gillio-Tos, Anna; De Marco, Laura; Rizzolo, Raffaella; Gustinucci, Daniela; Del Mistro, Annarosa; Frayle, Helena; Confortini, Massimo; Iossa, Anna; Cesarini, Elena; Bulletti, Simonetta; Passamonti, Basilio; Gori, Silvia; Toniolo, Laura; Barca, Alessandra; Bonvicini, Laura; Mancuso, Pamela; Venturelli, Francesco; Benevolo, Maria. - In: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - ISSN 0027-8874. - 113:3(2020), pp. 292-300. [10.1093/jnci/djaa105]

p16/ki67 and E6/E7 mRNA accuracy and prognostic value in triaging HPV DNA-positive women

Bonvicini, Laura;Venturelli, Francesco;
2020

Abstract

Background: The study presents cross-sectional accuracy of E6/E7 mRNA detection and p16/ki67 dual staining, alone or in combination with cytology and HPV16/18 genotyping, as triage test in HPV DNA-positive women and their impact on CIN2+ overdiagnosis. Methods: Women aged 25-64 were recruited. HPV DNA-positives were triaged with cytology and tested for E6/E7 mRNA and p16/ki67. Cytology positives were referred to colposcopy, while negatives were randomised to immediate colposcopy or to one-year HPV retesting. Lesions found within 24 months since recruitment were included. All p-values were two-sided. Results: 40,509 women were recruited and 3147 (7.8%) tested HPV DNA-positive; 174 CIN2+ were found: sensitivity was 61.0% (95% 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%. 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/cytology-negative women, relative CIN2+ detection in those randomized 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 negatives was about 2 times higher than in positive women (Pinteraction < .001 for both). Conclusions: p16/ki67 showed good performance as 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.
2020
3-ago-2020
113
3
292
300
p16/ki67 and E6/E7 mRNA accuracy and prognostic value in triaging HPV DNA-positive women / Rossi, Paolo Giorgi; Carozzi, Francesca; Ronco, Guglielmo; Allia, Elena; Bisanzi, Simonetta; Gillio-Tos, Anna; De Marco, Laura; Rizzolo, Raffaella; Gustinucci, Daniela; Del Mistro, Annarosa; Frayle, Helena; Confortini, Massimo; Iossa, Anna; Cesarini, Elena; Bulletti, Simonetta; Passamonti, Basilio; Gori, Silvia; Toniolo, Laura; Barca, Alessandra; Bonvicini, Laura; Mancuso, Pamela; Venturelli, Francesco; Benevolo, Maria. - In: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - ISSN 0027-8874. - 113:3(2020), pp. 292-300. [10.1093/jnci/djaa105]
Rossi, Paolo Giorgi; Carozzi, Francesca; Ronco, Guglielmo; Allia, Elena; Bisanzi, Simonetta; Gillio-Tos, Anna; De Marco, Laura; Rizzolo, Raffaella; Gu...espandi
File in questo prodotto:
File Dimensione Formato  
djaa105.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 1.01 MB
Formato Adobe PDF
1.01 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1208045
Citazioni
  • ???jsp.display-item.citation.pmc??? 19
  • Scopus 42
  • ???jsp.display-item.citation.isi??? 39
social impact