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p16/Ki67 dual stain triage versus cytology in primary human papillomavirus-based cervical cancer screening with limited genotyping
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  • Martyna Trzeszcz ,
  • Maciej Mazurec,
  • Robert Jach,
  • Karolina Mazurec,
  • Izabela Kotkowska-Szeps,
  • Magdalena Kania,
  • Mariola Wantuchowicz,
  • Jolanta Wasowska,
  • Monika Duczek-Polakiewicz,
  • Patrycja Rozmus,
  • Joanna Streb,
  • Agnieszka Halon
Martyna Trzeszcz
Corfamed Woman's Health Center

Corresponding Author:m.trzeszcz@corfamed.pl

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Maciej Mazurec
Corfamed Woman's Health Center
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Robert Jach
Uniwersytet Jagiellonski w Krakowie Collegium Medicum
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Karolina Mazurec
Corfamed Woman's Health Center
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Izabela Kotkowska-Szeps
Corfamed Woman's Health Center
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Magdalena Kania
Corfamed Woman's Health Center
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Mariola Wantuchowicz
Corfamed Woman's Health Center
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Jolanta Wasowska
Corfamed Woman's Health Center
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Monika Duczek-Polakiewicz
Corfamed Woman's Health Center
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Patrycja Rozmus
Corfamed Woman's Health Center
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Joanna Streb
Uniwersytet Jagiellonski w Krakowie Collegium Medicum
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Agnieszka Halon
Uniwersytet Medyczny im Piastow Slaskich we Wroclawiu
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Abstract

Background: The introduction of primary HPV cervical cancer screening requires the implementation of an appropriate triage strategy that will be effective in detecting high-grade cervical disease without losing diagnostic specificity. Methods: From the 30.066 screening tests results, a total of 1086 with available high-risk human papillomavirus (HRHPV) with limited genotyping, cytology and p16/Ki67 dual-stain were selected. Two triage strategies for primary HPV screening were analyzed retrospectively based on the study group. Performance characteristics for p16/Ki67 and cytology triage in detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) were calculated, detected in colposcopic biopsy. Results: In HPV16/18-positive cases, primary HPV with p16/Ki67 triage was significantly more specific than cytology (53.1%/16.8% for CIN2+; p<0.0001; 45.9%/17.0% for CIN3+; p<0.0001), with yielded sensitivity (95.7%/84.8% for CIN2+; p=0.0955; 100.0%/87.5% for CIN3+; p=0.0832). In other HRHPV-positive cases (N16/N18), p16/Ki67 triage was also significantly higher specific (51.3%/15.3% for CIN2+; p<0.0001; 44.5%/16.5% for CIN3+; p<0.0001), with sensitivity (92.3%/74.4% for CIN2+; p=0.0522; 90.9%/81.8% for CIN3+; p=0.5637). Diagnostic predictive values were significantly higher for p16/Ki67 triage with the highest PPV in HPV16/18-positive cases for CIN2+ (45.4%; 95% CI: 35.2-55.8; p<0.0001) and very high NPV in all HPV-positive cases regardless of detected genotype (96.3%-100.0%). The risk (1-NPV) for CIN3+ in HRHPV16/18-positive/p16/Ki67-negative women was 0.0%. Conclusions: Superior diagnostic performance compared to cytology for detecting cervical cancer precursors indicates that p16/Ki67 dual-immunostain may be a highly effective tool of triage in primary HPV screening with limited HPV 16/18 genotyping in the secondary cervical cancer prevention.
11 Aug 2023Submitted to Journal of Medical Virology
11 Aug 2023Submission Checks Completed
11 Aug 2023Assigned to Editor
11 Aug 2023Review(s) Completed, Editorial Evaluation Pending
14 Aug 2023Reviewer(s) Assigned
29 Aug 2023Editorial Decision: Revise Major
13 Nov 20231st Revision Received
14 Nov 2023Submission Checks Completed
14 Nov 2023Assigned to Editor
14 Nov 2023Review(s) Completed, Editorial Evaluation Pending
15 Nov 2023Editorial Decision: Accept