Accuracy of different triage strategies for human papillomavirus positivity in an Italian screening population

• Published in: International journal of cancer Vol. 150; no. 6; pp. 952 - 960
• Main Authors: Gustinucci, Daniela, Benevolo, Maria, Cesarini, Elena, Mancuso, Pamela, Passamonti, Basilio, Giaimo, Maria Donata, Corvetti, Rosa, Nofrini, Valeria, Bulletti, Simonetta, Malaspina, Morena, Tintori, Beatrice, Giorgi Rossi, Paolo
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15-03-2022; Wiley Subscription Services, Inc
• Subjects: accuracy; biomarkers; Cancer; Cancer screening; Cellular biology; Cervical cancer; cervical intraepithelial neoplasia; Cervical Intraepithelial Neoplasia - virology; Cervix; Colposcopy; Cyclin-Dependent Kinase Inhibitor p16 - analysis; Cytology; Female; Genotype; Genotyping; Human papillomavirus; Human papillomavirus 16 - genetics; Human papillomavirus 16 - isolation & purification; Human papillomavirus 18 - genetics; Human papillomavirus 18 - isolation & purification; Human Papillomavirus DNA Tests; Humans; Ki-67 Antigen - analysis; Medical research; Medical screening; screening; Triage; Uterine Cervical Neoplasms - virology; accuracy; screening; cervical cancer; biomarkers; cervical intraepithelial neoplasia
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.33858

How to manage human papillomavirus (HPV)‐positive women in cervical cancer screening remains debated. Our study compared different strategies to triage HPV positivity in a large cohort of women participating in a population HPV‐based screening program. Women were tested for HPV (Cobas 4800; Roche), and those positive were triaged with cytology; cytology‐positives were referred to colposcopy, while negatives were referred to 1‐year HPV retesting. All HPV‐positive women were also evaluated with p16/ki67 dual staining (Roche). All lesions found within 24 months of follow‐up were included in the analyses. Of the 70 146 women tested, 4757 (6.8%) were HPV‐positive. Of these, 1090 were cytology‐positive and were referred to colposcopy. Of the 2958 HPV‐positive/cytology‐negative women who presented at 1‐year retesting, 1752 (59.9%) still tested positive. Cumulatively, 532 CIN2+ (including 294 CIN3+) were found. The sensitivity of cytology, HPV16/18 and p16/ki67 as triage test for CIN3+ was 67.9%, 56.0% and 85.0%, respectively. The positive predictive value (PPV) for immediate colposcopy referral was 21.0%, 15.8% and 22.9%, respectively. Combining cytology with typing increased sensitivity to 83.9% and lowered PPV to 14.8%, while combining p16/ki67 and typing increased sensitivity to 91.1%, lowering the PPV to 15.9%. Women negative to p16/ki67 triage presented a cumulative 1‐year CIN3+ risk of about 1%. In conclusion, when triaging HPV positivity, p16/ki67 performed better than cytology with or without HPV16/18 genotyping. The strategies that included dual staining achieved sensitivity and low 1‐year risk for CIN3+ sufficiently high enough to permit considering extending the surveillance interval to 2 to 3 years for HPV‐positive/triage‐negative women.
What's new?
How to manage human papillomavirus (HPV)‐positive women in cervical cancer screening is still debated. In this large population‐based study, the authors evaluated the accuracy and performance of p16/ki67 dual staining, alone or in combination with HPV16/18 typing, as a triage test for HPV‐positive women in comparison with cytology. With or without HPV16/18 genotyping, p16/ki67 performed better than cytology in terms of both sensitivity and positive predictive value for CIN3+. The strategies that included dual staining achieved a high enough sensitivity with a low 1‐year risk of CIN3+ to potentially extend the current surveillance interval for HPV‐positive/triage‐negative women.