Serum ceruloplasmin levels for early detection of oral precancer and oral cancer—a systematic review and meta-analysis

Introduction: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the head and neck region. It frequently develops from oral potentially malignant disorders such as leukoplakia and oral submucous fibrosis, both of which carry a significant risk of malignant transformation. Early detection of OSCC is crucial for improving patient outcomes; however, current diagnostic approaches, including biopsy, are invasive and may lead to patient discomfort and anxiety. Serum ceruloplasmin (SCP), a copper-binding protein with oxidase activity, has shown potential as a less-invasive biomarker in various cancers, including OSCC. OSCC is often preceded by oral potentially malignant disorders (OPMDs); therefore, early detection at this stage is crucial for effective management and improved prognosis. This study combines a systematic review with a meta-analysis to assess serum ceruloplasmin levels for determining whether it can serve as a biomarker for the early detection of OPMDs and OSCC. Materials and methods: A systematic literature search was conducted using Google Scholar, PubMed, ProQuest, and Scopus databases. Studies included were original human research articles assessing serum ceruloplasmin levels in leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma, published in English up to 2024. Eight studies that met these criteria were included. The review followed PRISMA guidelines and was registered in PROSPERO. Meta-analysis was conducted using a random-effects model. Forest plots were generated to illustrate SCP levels in the three study groups. Results: Serum ceruloplasmin levels demonstrated a progressive increase from normal mucosa to leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma. Both leukoplakia and oral submucous fibrosis showed significantly higher serum ceruloplasmin levels than normal tissue, suggesting a progressive association between ceruloplasmin concentration and lesion severity. Also, oral squamous cell carcinoma exhibited the highest serum ceruloplasmin concentrations. However, the difference between oral squamous cell carcinoma and oral submucous fibrosis was minimal, indicating overlapping values. Conclusion: Elevated serum ceruloplasmin levels may serve as a promising non-invasive biomarker for early detection of oral potentially malignant disorders and oral squamous cell carcinoma. Standardized methodologies and larger-scale studies are warranted to validate serum ceruloplasmin's diagnostic utility.