{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T08:15:42Z","timestamp":1759565742687,"version":"3.33.0"},"reference-count":52,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T00:00:00Z","timestamp":1468800000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tumori"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p> This systematic review of 43 studies aims to evaluate the absolute and relative sensitivity and specificity of p16<jats:sup>INK4a<\/jats:sup> with regard to uterine cervix lesions, describing innovations and techniques for the detection of high-grade cervical dysplasia and allowing correct treatment. Studies were identified in the PubMed database up to March 2015. The keywords hrHPV, p16<jats:sup>INK4a<\/jats:sup> gene, and uterine cervical disease (MeSH terms) were used. Only English-language articles were included. We considered retrospective and prospective studies that assessed p16<jats:sup>INK4a<\/jats:sup> or p16<jats:sup>INK4a<\/jats:sup>\/Ki67 staining, with or without HPV-DNA testing (HC2\/PCR) as a comparator test, in cytological\/histological specimens for which the diagnosis of ASCUS, LSIL or HSIL was verified with a reference standard. The primary outcome for cervical lesions was evaluation of the absolute p16<jats:sup>INK4a<\/jats:sup> immunoreactivity; the secondary outcome was evaluation of the relative p16<jats:sup>INK4a<\/jats:sup> immunoreactivity versus HPV testing in those studies where comparator tests were available. p16<jats:sup>INK4a<\/jats:sup> was more specific than HPV-DNA test (median values of 56.1% vs. 52.25% in CIN grade \u22652 lesions; 82.5% vs. 53% in negative and CIN grade \u22651 lesions). The main limitation of this study is linked to both qualitative and quantitative p16<jats:sup>INK4a<\/jats:sup> levels of expression, while the second limitation is the lack of standardized scales. p16<jats:sup>INK4a<\/jats:sup> and HPV-DNA used together increased the sensitivity and negative predictive value for CIN detection. p16<jats:sup>INK4a<\/jats:sup> can be considered a biomarker of CIN2 or CIN3, indicating a high risk of relapse or evolution to invasive carcinoma. Also p16<jats:sup>INK4a<\/jats:sup>-negative CIN should be considered and further research should be performed. <\/jats:p>","DOI":"10.5301\/tj.5000524","type":"journal-article","created":{"date-parts":[[2016,7,25]],"date-time":"2016-07-25T08:19:26Z","timestamp":1469434766000},"page":"450-458","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Management of HPV-Related Cervical Disease: Role of p16<sup>INK4a<\/sup> Immunochemistry. 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