{ "abstract": "Background: Oral squamous cell carcinoma (OSCC) has a relatively poor survival, and TNM staging alone offers limited prognostic discrimination. C-reactive protein (CRP) is a non-specific inflammatory marker and is one of the most studied candidate prognostic biomarkers of OSCC, while CYFRA 21-1 and squamous cell carcinoma antigen (SCC-Ag) are tumor-derived keratin proteins reflecting malignant cell turnover, often examined alongside CRP. However, no prior review has synthesized the value of these three markers together in OSCC. Methods: Following the PRISMA 2020 guidelines, PubMed, Embase, and Web of Science were searched for studies reporting an extractable hazard ratio (HR), odds ratio, or comparable association of serum and/or salivary CYFRA 21-1, SCC-Ag, and/or CRP with disease-free survival (DFS), recurrence, or overall survival (OS) in OSCC. HRs were pooled using Knapp-Hartung random-effects models, wherever at least two independent cohorts contributed; salivary CYFRA 21-1 and recurrence were pooled as a standardized mean difference (SMD). Studies reporting only cross-sectional associations with tumor stage, grade, or metastasis and non-independent (same-registry) studies were synthesized descriptively following Synthesis without Meta-analysis (SWiM) guidance. Risk of bias was assessed with QUIPS and certainty of evidence with the GRADE framework. Results: Twenty-eight studies were included (21 quantitative, 7 narrative), representing ~3500 study participants across published cohorts, with some overlap between studies. For OS, two independently pooled single-marker estimates were both non-significant: serum SCC-Ag alone (n = 2, HR 1.43, 95% CI: 0.09-23.14, p = 0.35, I² = 66%) and serum CRP alone (n = 5, HR 1.33, 95% CI: 0.89-1.99, I² = 52%). A further seven non-independent, same-registry studies reporting combined SCC-Ag + CRP or single-marker models ranged from HR 1.82 to 11.11, directionally consistent with the pooled estimates. For DFS, pooled serum CYFRA 21-1 alone gave HR 1.61 (95% CI: 0.39-6.61; p = 0.15, I² = 0%), with six further non-independent or single-study estimates (HR 1.38-4.05) in the same direction. For recurrence, pooled salivary CYFRA 21-1 gave an SMD of Hedges' g = 0.79 (95% CI: 0.04-1.55; p = 0.048, I² = 0%). All outcomes were rated very low certainty by GRADE. Conclusions: Within the limitations of the study and the small number of contributing studies, salivary CYFRA 21-1 showed some prognostic value for recurrence, while pooled estimates for serum CRP alone, serum SCC-Ag alone, and serum CYFRA 21-1 alone for DFS all trended toward increased risk but did not reach statistical significance. Given the very low evidence certainty, these findings are hypothesis-generating and require further validation in independent, multicenter, prospective cohorts before clinical application.", "abstract_shown": true, "affiliations": [ "Department of Dentistry, Komar University of Science and Technology, Sulaimani 46001, Iraq.", "Bio-Cultural Anthropology, Law, Ethics and Health Laboratory (ADES), Faculty of Medical and Paramedical Sciences, Aix-Marseille University, French National Center of Scientific Research (CNRS), French Blood Establishment (EFS), 13005 Marseille, France.", "College of Medicine, Sulaymaniyah University, Sulaymaniyah 46001, Iraq.", "Health Systemic Process (P2S) UR4129, Université Lyon 1, 69008 Lyon, France.", "Department of Oral Surgery, Timone Hospital, Assistance Publique-Hôpitaux de Marseille, 13385 Marseille, France." ], "article_type": "systematic review", "arxiv": null, "author_total": 7, "authors": [ { "affs": [ 0 ], "name": "Balen Hamid Qadir" }, { "affs": [ 1 ], "name": "Mohammed Khalid Mahmood", "orcid": "0000-0002-8093-9514" }, { "affs": [ 2 ], "name": "Hazha Abdulla Mohammed Ameen" }, { "affs": [ 0 ], "name": "Yad Mariwan Mohammed Amin" }, { "affs": [ 2 ], "name": "Ariwan Othman Saeed" }, { "affs": [ 3 ], "name": "Florence Carrouel", "orcid": "0000-0002-6823-1636" }, { "affs": [ 1, 4 ], "name": "Romain Lan", "orcid": "0000-0002-5612-880X" } ], "bibtex": "https://research.draconitic.com/paper/dp5prwbema1mb.bib", "cited_by": 0, "doi": "10.3390/medsci14060610", "fulltext_url": "https://europepmc.org/articles/PMC13707081", "id": "dp5prwbema1mb", "issns": [ "2076-3271" ], "landing_url": "https://hal.science/hal-05766304v1", "language": "en", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "hal", "0.sdv" ], [ "openalex", "2733|Head and Neck Cancer Studies" ] ], "openalex": "W7214638428", "pdf_url": "https://hal.science/hal-05766304/document", "pmcid": "PMC13707081", "pmid": "42930529", "published": "2026-09-27", "publisher": "MDPI", "ris": "https://research.draconitic.com/paper/dp5prwbema1mb.ris", "sources": [ { "first_seen": "2026-10-30T12:17:41Z", "native_id": "hal-05766304", "source": "hal", "url": "https://hal.science/hal-05766304v1" }, { "first_seen": "2026-10-30T12:22:01Z", "native_id": "MED:42930529", "source": "europepmc", "url": "https://europepmc.org/article/MED/42930529" } ], "subjects": [ { "field": "biology", "origin": "hal:0.sdv", "subfield": "general" } ], "title": "Prognostic Value and Stage/Nodal Correlates of Serum and Salivary CRP, CYFRA 21-1, and SCC-Ag Biomarkers in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis", "title_text": "Prognostic Value and Stage/Nodal Correlates of Serum and Salivary CRP, CYFRA 21-1, and SCC-Ag Biomarkers in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis", "type": "peer-reviewed", "updated_at": "2026-10-30T12:22:01Z", "url": "https://research.draconitic.com/paper/dp5prwbema1mb", "venue": "Medical Sciences", "versions": [] }