{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T08:18:10Z","timestamp":1793521090067,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,7]],"date-time":"2023-05-07T00:00:00Z","timestamp":1683417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health (Ricerca Corrente)"},{"name":"CRO"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The prevalence and incidence of oropharyngeal squamous cell carcinomas (OPSCCs) driven by human papillomavirus (HPV) infection are increasing worldwide, being higher in high-income countries. However, data from Italy are scanty. p16INK4a overexpression is the standard in determining HPV-driven carcinogenesis, but disease prevalence impacts on its positive predictive value. Methods: This is a multicenter retrospective study enrolling 390 consecutive patients aged \u226518 years, diagnosed with pathologically confirmed OPSCC in Northeastern Italy between 2000 and 2022. High-risk HPV-DNA and p16INK4a status were retrieved from medical records or evaluated in formalin-fixed paraffin-embedded specimens. A tumor was defined as HPV-driven when double positive for high-risk HPV-DNA and p16INK4a overexpression. Results: Overall, 125 cases (32%) were HPV-driven, with a significant upward temporal trend from 12% in 2000\u20132006 to 50% in 2019\u20132022. The prevalence of HPV-driven cancer of the tonsil and base of the tongue increased up to 59%, whereas it remained below 10% in other subsites. Consequently, the p16INK4a positive predictive value was 89% for the former and 29% for the latter. Conclusions: The prevalence of HPV-driven OPSCC continued to increase, even in the most recent period. When using p16INK4a overexpression as a surrogate marker of transforming HPV infection, each institution should consider the subsite-specific prevalence rates of HPV-driven OPSCC as these significantly impact on its positive predictive value.<\/jats:p>","DOI":"10.3390\/cancers15092643","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T02:03:31Z","timestamp":1683511411000},"page":"2643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Rising Trend in the Prevalence of HPV-Driven Oropharyngeal Squamous Cell Carcinoma during 2000\u20132022 in Northeastern Italy: Implication for Using p16INK4a as a Surrogate Marker for HPV-Driven Carcinogenesis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-7959","authenticated-orcid":false,"given":"Paolo","family":"Boscolo-Rizzo","sequence":"first","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9381-1520","authenticated-orcid":false,"given":"Jerry","family":"Polesel","sequence":"additional","affiliation":[{"name":"Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-9374","authenticated-orcid":false,"given":"Annarosa","family":"Del Mistro","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Fratta","sequence":"additional","affiliation":[{"name":"Unit of Immunopathology and Cancer Biomarkers, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Lazzarin","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Menegaldo","sequence":"additional","affiliation":[{"name":"Unit of Otolaryngology, AULSS 2 Marca Trevigiana, Piazzale dell\u2019Ospedale 1, 31100 Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Lupato","sequence":"additional","affiliation":[{"name":"Unit of Otolaryngology, General Hospital \u201cS. Maria degli Angeli\u201d, Via Montereale 24, 33170 Pordenone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9677-3176","authenticated-orcid":false,"given":"Giuseppe","family":"Fanetti","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Zanconati","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, Section of Pathology, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Guido","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Pathology, University of Padova, via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Giacomarra","sequence":"additional","affiliation":[{"name":"Unit of Otolaryngology, General Hospital \u201cS. Maria degli Angeli\u201d, Via Montereale 24, 33170 Pordenone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2422-5402","authenticated-orcid":false,"given":"Enzo","family":"Emanuelli","sequence":"additional","affiliation":[{"name":"Unit of Otolaryngology, AULSS 2 Marca Trevigiana, Piazzale dell\u2019Ospedale 1, 31100 Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Tofanelli","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Tirelli","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/ijc.30716","article-title":"Worldwide Burden of Cancer Attributable to HPV by Site, Country and HPV Type","volume":"141","author":"Plummer","year":"2017","journal-title":"Int. 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