The CERTAIN Study Results: Adjunctive p16 Immunohistochemistry Use in Cervical Biopsies According to LAST Criteria.
Biomarkers, Tumor
/ analysis
Biopsy
Cyclin-Dependent Kinase Inhibitor p16
/ analysis
False Negative Reactions
False Positive Reactions
Female
Humans
Immunohistochemistry
Neoplasm Grading
Observer Variation
Predictive Value of Tests
Reproducibility of Results
Squamous Intraepithelial Lesions of the Cervix
/ metabolism
Uterine Cervical Neoplasms
/ chemistry
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
pubmed:
8
7
2021
medline:
5
10
2021
entrez:
7
7
2021
Statut:
ppublish
Résumé
The Lower Anogenital Squamous Terminology (LAST) Project recommends the use of p16 immunohistochemistry as an adjunct to morphologic assessment of cervical biopsies according to a specific set of criteria. We analyzed the effect of adjunctive p16 according to LAST criteria in a US-based diagnostic utility study involving 70 surgical pathologists providing a total of 38,500 reads on cervical biopsies. Compared with the results obtained using hematoxylin and eosin-stained slides only, including p16-stained slides per LAST criteria increased sensitivity and specificity for diagnosing histologic high-grade squamous intraepithelial lesions across all cases by 8.1% (95% confidence interval [95% CI], 6.5-9.7; P<0.0001) and 3.5% (95% CI, 2.8-4.2; P<0.0001), respectively, using expert consensus diagnoses on hematoxylin and eosin+p16 as reference. Within the subset of cases classified by the pathologists as fulfilling the LAST criteria, adding p16 significantly increased both sensitivity (+11.8%; 95% CI, 9.5-14.0; P<0.0001) and specificity (+9.7%; 95% CI, 7.8-11.5; P<0.0001). However, a comparable improvement in sensitivity (+11.0%; 95% CI, 7.8-14.1; P<0.0001) was found when p16 was used in cases for which p16 staining was not ordered per LAST by the pathologists, whereas specificity decreased by -0.8% (95% CI, -1.1 to -0.5; P<0.0001). The study demonstrates a clinically and statistically significant increase in sensitivity and specificity for high-grade squamous intraepithelial lesion when p16 is used according to LAST criteria. Expanding the use of p16 into non-LAST cases would lead to a comparable improvement in sensitivity within this subgroup of biopsies, at the cost of a minimal, but statistically significant difference in specificity.
Identifiants
pubmed: 34232603
pii: 00000478-202110000-00006
doi: 10.1097/PAS.0000000000001709
doi:
Substances chimiques
Biomarkers, Tumor
0
CDKN2A protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1348-1356Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: T.C.W. and M.H.S. are consultants to Ventana Medical Systems Inc (Roche Tissue Diagnostics), Roche Molecular Diagnostics, BD Lifesciences, and Inovio. They also are speakers for Ventana Medical Systems Inc (Roche Tissue Diagnostics), Roche Molecular Diagnostics, and BD Lifesciences at various symposia. A.F. is a consultant to Ventana Medical Systems Inc (Roche Tissue Diagnostics). The other authors are employees of Ventana Medical Systems Inc (Roche Tissue Diagnostics) which commercializes in vitro diagnostic products evaluated in this study.
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