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\begin{document}

\title{p16/Ki67 dual stain triage versus cytology in primary human
papillomavirus-based cervical cancer screening with limited genotyping}



\author[1]{Martyna  Trzeszcz }%
\author[1]{Maciej Mazurec}%
\author[2]{Robert  Jach}%
\author[1]{Karolina Mazurec}%
\author[1]{Izabela Kotkowska-Szeps}%
\author[1]{Magdalena Kania}%
\author[1]{Mariola Wantuchowicz}%
\author[1]{Jolanta Wasowska}%
\author[1]{Monika Duczek-Polakiewicz}%
\author[1]{Patrycja Rozmus}%
\author[2]{Joanna Streb}%
\author[3]{Agnieszka Halon}%
\affil[1]{Corfamed Woman's Health Center}%
\affil[2]{Uniwersytet Jagiellonski w Krakowie Collegium Medicum}%
\affil[3]{Uniwersytet Medyczny im Piastow Slaskich we Wroclawiu}%


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  \date{May 22, 2024}


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\begin{abstract}
\textbf{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. \textbf{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. \textbf{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\textless{}0.0001; 45.9\%/17.0\% for CIN3+;
p\textless{}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\textless{}0.0001; 44.5\%/16.5\% for CIN3+;
p\textless{}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\textless{}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\%.
\textbf{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.%
\end{abstract}%



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\textbf{Hosted file}

\verb`JMV Manuscript.docx`  available at \url{https://authorea.com/users/651597/articles/659494-p16-ki67-dual-stain-triage-versus-cytology-in-primary-human-papillomavirus-based-cervical-cancer-screening-with-limited-genotyping}

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