Clinical validation of p16/Ki-67 dual-stained cytology triage of HPV-positive women: Results from the IMPACT trial.
Adult
Aged
Colposcopy
Cyclin-Dependent Kinase Inhibitor p16
/ analysis
Female
Genotype
Human papillomavirus 16
/ isolation & purification
Human papillomavirus 18
/ isolation & purification
Humans
Immunohistochemistry
Ki-67 Antigen
/ analysis
Middle Aged
Prospective Studies
Triage
Uterine Cervical Neoplasms
/ chemistry
HPV testing
cervical cancer
p16/Ki-67 dual-stain
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
revised:
24
08
2021
received:
19
07
2021
accepted:
27
08
2021
pubmed:
19
9
2021
medline:
17
2
2022
entrez:
18
9
2021
Statut:
ppublish
Résumé
Triage strategies are needed for primary human papillomavirus (HPV)-based cervical cancer screening to identify women requiring colposcopy/biopsy. We assessed the performance of p16/Ki-67 dual-stained (DS) immunocytochemistry to triage HPV-positive women and compared it to cytology, with or without HPV16/18 genotyping. A prospective observational screening study enrolled 35 263 women aged 25 to 65 years at 32 U.S. sites. Cervical samples had HPV and cytology testing, with colposcopy/biopsy for women with positive tests. Women without cervical intraepithelial neoplasia Grade 2 or worse (≥CIN2) at baseline (n = 3876) were retested after 1 year. In all, 4927 HPV-positive women with valid DS results were included in this analysis. DS sensitivity for ≥CIN2 and ≥CIN3 at baseline was 91.2% (95% confidence interval [CI]: 86.8%-94.2%) and 91.9% (95% CI: 86.1%-95.4%), respectively, in HPV16/18-positive women and 83.0% (95% CI: 78.4%-86.8%) and 86.0% (95% CI: 77.5%-91.6%) in women with 12 "other" genotypes. Using DS alone to triage HPV-positive women showed significantly higher sensitivity and specificity than HPV16/18 genotyping with cytology triage of 12 "other" genotypes, and substantially higher sensitivity but lower specificity than using cytology alone. The risk of ≥CIN2 was significantly lower in HPV-positive, DS-negative women (3.6%; 95% CI: 2.9%-4.4%), compared to triage-negative women using HPV16/18 genotyping with cytology for 12 "other" genotypes (7.4%; 95% CI: 6.4%-8.5%; P < .0001) or cytology alone (7.5%; 95% CI: 6.7%-8.4%; P < .0001). DS showed better risk stratification than cytology-based strategies and provided high reassurance against pre-cancers both at baseline and at 1-year follow-up, irrespective of the HPV genotype. DS allows for the safe triage of primary screening HPV-positive women.
Identifiants
pubmed: 34536311
doi: 10.1002/ijc.33812
pmc: PMC9293341
doi:
Substances chimiques
CDKN2A protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
Ki-67 Antigen
0
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
461-471Informations de copyright
© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Références
Cancer Epidemiol Biomarkers Prev. 2020 Jun;29(6):1246-1252
pubmed: 32156721
Gynecol Oncol. 2017 Jan;144(1):51-56
pubmed: 28094038
J Low Genit Tract Dis. 2012 Jul;16(3):205-42
pubmed: 22820980
Int J Cancer. 2018 Aug 15;143(4):735-745
pubmed: 29341110
Am J Obstet Gynecol. 2012 Jan;206(1):46.e1-46.e11
pubmed: 21944226
Int J Cancer. 2022 Feb 1;150(3):461-471
pubmed: 34536311
Cancer Cytopathol. 2015 Apr;123(4):212-8
pubmed: 25534957
Gynecol Oncol. 2015 Feb;136(2):178-82
pubmed: 25579107
J Clin Virol. 2016 Mar;76 Suppl 1:S49-S55
pubmed: 26643050
Gynecol Oncol. 2015 Feb;136(2):189-97
pubmed: 25579108
Int J Cancer. 2020 May 1;146(9):2599-2607
pubmed: 31490545
Lancet Oncol. 2011 Sep;12(9):880-90
pubmed: 21865084
JAMA Oncol. 2019 Feb 1;5(2):181-186
pubmed: 30325982
Gynecol Oncol. 2011 Jun 1;121(3):505-9
pubmed: 21420158
Cancer Cytopathol. 2017 Mar;125(3):212-220
pubmed: 27926800
Gynecol Oncol. 2018 Jun;149(3):498-505
pubmed: 29681462
JAMA Intern Med. 2019 Jul 1;179(7):881-888
pubmed: 31081870
J Low Genit Tract Dis. 2020 Apr;24(2):90-101
pubmed: 32243306
J Natl Cancer Inst. 2021 Mar 1;113(3):292-300
pubmed: 32745170
J Low Genit Tract Dis. 2020 Apr;24(2):102-131
pubmed: 32243307
Cancer Cytopathol. 2015 Jun;123(6):373-81
pubmed: 25891096
J Natl Cancer Inst. 2015 Sep 15;107(12):djv257
pubmed: 26376685
J Natl Cancer Inst. 2013 Oct 16;105(20):1550-7
pubmed: 24096620
Am J Obstet Gynecol. 2021 Sep;225(3):278.e1-278.e16
pubmed: 33852886