Clinical Value of Serum HMGB1 Levels in Early Detection of Recurrent Squamous Cell Carcinoma of Uterine Cervix: Comparison with Serum SCCA, CYFRA21-1, and CEA Levels

Aim To evaluate the clinical value of serum high mobility group box chromosomal protein 1 (HMGB1) levels in making the early diagnosis of recurrent cervical squamous cell carcinomas (CSCC) and compare it with the value of serum squamous cell carcinoma antigen (SCCA), cytokeratin fragment (CYFRA) 21-1, and carcinoembryonic antigen (CEA) levels. Methods Immunohistochemical staining of tissue from 64 patients with recurrent CSCCs, 72 patients with non-recurrent carcinoma, and 28 healthy participants was performed to determine the expression of HMGB1 protein. The serum levels of the 4 markers in 112 patients with recurrent CSCC, 174 patients with non-recurrent disease, and 128 healthy participants were measured by enzyme-linked immunosorbent assay. The receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was calculated. Results Higher immunostaining score was found in recurrent CSCC tissue sections than in non-recurrent CSCC sections. Serum HMGB1 levels in patients with recurrent CSCC were significantly higher than in patients with non-recurrent disease and healthy controls. The AUC of HMGB1, SCCA, CYFRA21-1, and CEA was 0.816, 0.768, 0.703, and 0.625, respectively. HMGB1 had the best specificity and positive likelihood ratio (78.0% and 3.25, respectively), whereas SCCA had the best sensitivity and negative likelihood ratio (76.3% and 0.34, respectively). Parallel combined measurements increased the diagnostic sensitivity and serial combination increased the specificity. High serum HMGB1 levels were inversely correlated with disease-free survival (P=0.009, Pearson X-2 test) and overall survival (P=0.018). Conclusion HMGB1 was overexpressed in recurrent CSCCs. Serum HMGB1 level could be a useful and specific marker for evaluating the disease recurrence and predicting prognosis in patients with CSCC. Serial combined measurements of serum HMGB1, SCCA, and CYFRA21-1 increased the diagnostic specificity, and parallel combined testing increased the diagnostic sensitivity.