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Patients Regardless of HPV Status  \nLucija Luli´c 1,2, Ivana Šimi´c 1, Ksenija Božinovi´c 2, Ena Pešut 1, Luka Manojlovi´c 3, Magdalena Grce 1, Emil Dediol 4, Ivan Sabol 1, * and Vjekoslav Tomai´c 1, *  \nCitation: Luli´c, L.; Šimi´c, I.; Božinovi´c, K.; Pešut, E.; Manojlovi´c, L.; Grce, M.; Dediol, E.; Sabol, I.; Tomai´c, V. Moderate SCRIB Expression Levels Correlate with Worse Prognosis in OPSCC Patients Regardless of HPV Status. Cells 2024, 13, 1002. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells13121002  \nAcademic Editor: Jozsef Dudas  \nReceived: 25 April 2024  \nRevised: 29 May 2024  \nAccepted: 4 June 2024  \nPublished: 8 June 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Division of Molecular Medicine, Ruer Boškovi´c Institute, Bijeniˇcka Cesta 54, 10000 Zagreb, Croatia; [lucija.lulic@irb.hr](lucija.lulic@irb.hr) (L.L.)  \n2 Division of Molecular Biology, Ruer Boškovi´c Institute, Bijeniˇcka Cesta 54, 10000 Zagreb, Croatia  \n3 Department of Pathology and Cytology, University Hospital Dubrava, 10000 Zagreb, Croatia  \n4 Department of Maxillofacial Surgery, University Hospital Dubrava, 10000 Zagreb, Croatia  \n* Correspondence: [isabol@irb.hr](isabol@irb.hr) (I.S.); [tomaic@irb.hr](tomaic@irb.hr) (V.T.)  \nAbstract: Head and neck cancers rank as the sixth most prevalent cancers globally. In addition to traditional risk factors such as smoking and alcohol use, human papillomavirus (HPV) infections are becoming a significant causative agent of head and neck cancers, particularly among Western populations. Although HPV offers a significant survival benefit, the search for better biomarkers is still ongoing. In the current study, our objective was to investigate whether the expression levels of three PDZ-domain-containing proteins (SCRIB, NHERF2, and DLG1), known HPV E6 cellular substrates, influence the survival of HNSCC patients treated by primary surgery (n = 48) . Samples were derived from oropharyngeal and oral cancers, and HPV presence was confirmed by PCR and p16 staining. Clinical and follow-up information was obtained from the hospital database and the Croatian Cancer registry up to November 2023 . Survival was evaluated using the Kaplan–Meier method and Cox proportional hazard regression. The results were corroborated through the reanalysis of a comparable subset of TCGA cancer patients (n = 391) . In conclusion, of the three targets studied, only SCRIB levels were found to be an independent predictor of survival in the Cox regression analysis, along with tumor stage. Further studies in a more typical Western population setting are needed since smoking and alcohol consumption are still prominent in the Croatian population, while the strongest association between survival and SCRIB levels was seen in HPV-negative cases.  \nKeywords: HPV; survival; SCRIB; NHERF2; DLG1; HNSCC; E6  \n1. Introduction  \nHead and neck cancers (HNCs) are the sixth most common cancers worldwide, with an incidence of around 600 000 cases per year [1,2] . Head and neck squamous cell carcinomas (HNSCCs), derived from the mucosal epithelium in the upper aerodigestive tract, represent more than 90% of HNCs [1] . These cancers share similar risk factors, including smoking, tobacco chewing, alcohol consumption (~75% of HNSCC cases), and human papillomavirus (HPV) (~25% of HNSCC cases) [3–5] . HPV is particularly linked to oropharyngeal squamous cell carcinoma (OPSCC), which frequently occurs in the tonsils, base of the tongue, soft palate, and uvula [6] . Up to 96% of these tumors are HPV16-positive (HPV16+) and, in c","cbCaigAmlHMREuRh","https://ap.wps.com/l/cbCaigAmlHMREuRh","pdf",1733118,13,"English","# Introduction\n## Risk factors and HPV in head and neck cancer\n## Survival differences in HPV-positive OPSCC\n## HPV biology and study rationale","[{\"question\":\"What is the main objective of the study?\",\"answer\":\"To determine whether expression levels of SCRIB, NHERF2, and DLG1 influence survival in OPSCC patients treated by primary surgery.\"},{\"question\":\"How was HPV status determined in the patient cohort?\",\"answer\":\"HPV presence was confirmed using PCR and p16 staining, with clinical and follow-up data retrieved from hospital records and the Croatian Cancer registry.\"},{\"question\":\"Which biomarker showed independent prognostic value?\",\"answer\":\"Only SCRIB expression levels were identified as an independent predictor of survival in Cox regression analysis, alongside tumor stage.\"}]","Moderate SCRIB Expression Levels Correlate with Worse Prognosis in OPSCC Patients Regardless of HPV Status | PDF",1790002637,33]