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Patients with HPV-induced cancer respond better to treatment and consequently have lower case-fatality rates than patients with HPV-unrelated OPC. These considerations highlight the importance of reliable and accurate markers to diagnose truly HPV-induced OPC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The accuracy of three possible test strategies, i.e. (a) hrHPV DNA PCR (DNA), (b) p16<jats:sup>(INK4a)<\/jats:sup> immunohistochemistry (IHC) (p16), and (c) the combination of both tests (considering joint DNA and p16 positivity as positivity criterion), was analysed in tissue samples from 99 Belgian OPC patients enrolled in the HPV-AHEAD study. Presence of HPV E6*I mRNA (mRNA) was considered as the reference, indicating HPV etiology.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Ninety-nine OPC patients were included, for which the positivity rates were 36.4%, 34.0% and 28.9% for DNA, p16 and mRNA, respectively. Ninety-five OPC patients had valid test results for all three tests (DNA, p16 and mRNA). Using mRNA status as the reference, DNA testing showed 100% (28\/28) sensitivity, and 92.5% (62\/67) specificity for the detection of HPV-driven cancer. p16 was 96.4% (27\/28) sensitive and equally specific (92.5%; 62\/67). The sensitivity and specificity of combined p16\u2009+\u2009DNA testing was 96.4% (27\/28) and 97.0% (65\/67), respectively. In this series, p16 alone and combined p16\u2009+\u2009DNA missed 1 in 28 HPV driven cancers, but p16 alone misclassified 5 in 67 non-HPV driven as positive, whereas combined testing would misclassify only 2 in 67.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Single hrHPV DNA PCR and p16<jats:sup>(INK4a)<\/jats:sup> IHC are highly sensitive but less specific than using combined testing to diagnose HPV-driven OPC patients. Disease prognostication can be encouraged based on this combined test result.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12879-022-07654-2","type":"journal-article","created":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T17:03:56Z","timestamp":1659805436000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Accuracy of high-risk HPV DNA PCR, p16(INK4a) immunohistochemistry or the combination of both to diagnose HPV-driven oropharyngeal 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Ethical clearance was obtained from the Ethical Committees of \u2018GZA hospitals\u2019 (ref nb: BVDE\/hp\/2013\/01.147), \u2018UZA & UA (University of Antwerp)\u2019 (ref nb: 11\/47\/362) and IARC, Lyon, France (ref nb: 11\u201330). Informed consent of the individual patient was not necessary, as it concerns biobank-based research. The ethical principles, detailed by a European network specialized in biobanking (Hansson MG, Methods Mol.Biol 2011; 675:39\u201359), are respected. The need of informed consent was waived by the Ethical Committees of \u2018GZA hospitals\u2019 and \u2018UZA & UA (University of Antwerp)\u2019 for the Belgian patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"RR and SR are employees of Roche. All other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"676"}}