Combined use of cytology, p16 immunostaining and genotyping for triage of women positive for high-risk human papillomavirus at primary screening.
Adult
Colposcopy
Cross-Sectional Studies
Cyclin-Dependent Kinase Inhibitor p16
/ metabolism
Early Detection of Cancer
Female
Genotyping Techniques
/ methods
Humans
Middle Aged
Papillomaviridae
/ genetics
Papillomavirus Infections
/ metabolism
Predictive Value of Tests
Triage
Uterine Cervical Neoplasms
/ diagnosis
Vaginal Smears
/ methods
Uterine Cervical Dysplasia
/ diagnosis
HPV genotyping
HPV testing
cervical screening
cytology
p16 immunocytochemistry
triage of HPV-positive women
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 10 2020
01 10 2020
Historique:
received:
18
11
2019
revised:
07
02
2020
accepted:
28
02
2020
pubmed:
15
3
2020
medline:
10
4
2021
entrez:
15
3
2020
Statut:
ppublish
Résumé
Human papillomavirus (HPV) testing is very sensitive for primary cervical screening but has low specificity. Triage tests that improve specificity but maintain high sensitivity are needed. Women enrolled in the experimental arm of Phase 2 of the New Technologies for Cervical Cancer randomized controlled cervical screening trial were tested for high-risk HPV (hrHPV) and referred to colposcopy if positive. hrHPV-positive women also had HPV genotyping (by polymerase chain reaction with GP5+/GP6+ primers and reverse line blotting), immunostaining for p16 overexpression and cytology. We computed sensitivity, specificity and positive predictive value (PPV) for different combinations of tests and determined potential hierarchical ordering of triage tests. A number of 1,091 HPV-positive women had valid tests for cytology, p16 and genotyping. Ninety-two of them had cervical intraepithelial neoplasia grade 2+ (CIN2+) histology and 40 of them had CIN grade 3+ (CIN3+) histology. The PPV for CIN2+ was >10% in hrHPV-positive women with positive high-grade squamous intraepithelial lesion (61.3%), positive low-grade squamous intraepithelial lesion (LSIL+) (18.3%) and positive atypical squamous cells of undetermined significance (14.8%) cytology, p16 positive (16.7%) and, hierarchically, for infections by HPV33, 16, 35, 59, 31 and 52 (in decreasing order). Referral of women positive for either p16 or LSIL+ cytology had 97.8% sensitivity for CIN2+ and women negative for both of these had a 3-year CIN3+ risk of 0.2%. Similar results were seen for women being either p16 or HPV16/33 positive. hrHPV-positive women who were negative for p16 and cytology (LSIL threshold) had a very low CIN3+ rate in the following 3 years. Recalling them after that interval and referring those positive for either test to immediate colposcopy seem to be an efficient triage strategy. The same applies to p16 and HPV16.
Substances chimiques
CDKN2A protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1864-1873Informations de copyright
© 2020 UICC.
Références
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