Diagnostic accuracy of SCCA and SCCA-IgM for hepatocellular carcinoma: A meta-analysis

Liver Int. 2018 Oct;38(10):1820-1831. doi: 10.1111/liv.13867. Epub 2018 May 22.


Background & aims: Squamous cell carcinoma antigen (SCCA) and its immune complex (SCCA-IgM) have been proposed for use in the screening of hepatocellular carcinoma (HCC). We conducted a meta-analysis to evaluate the diagnostic performance of SCCA and SCCA-IgM and of both combined with alpha-foetoprotein.

Methods: After a systematic review of the relevant studies, the sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio (DOR) and area under curve (AUC) for the diagnosis of HCC were pooled using bivariate meta-analysis. Hierarchic summary receiver operating characteristic curves were used to summarize the overall test performance. Bivariate boxplots were used to confirm whether the threshold effect existed. A Fagan nomogram was used to assess the clinical utility. Heterogeneity was explored by sensitivity analysis, univariable meta-regression and subgroup analysis.

Results: Eleven studies that had HCC diagnosis as their purpose were ultimately included in the quantitative analysis. The summary estimates were as follows: SCCA (AUC: 0.80 [95% CI: 0.76-0.83]) and SCCA-IgM (AUC: 0.77 [95% CI: 0.74-0.83]) demonstrated similar diagnostic performance, while a combination of AFP and SCCA-IgM had an AUC of 0.90 (95% CI: 0.87-0.92) and a DOR of 22.87 (95% CI: 8.38-62.40). Meta-regression showed that patient selection, cut-off values, reference standards and tumour biopsy as the diagnostic method significantly influenced the heterogeneity of the included studies.

Conclusions: Both SCCA and SCCA-IgM showed a moderate diagnostic accuracy for HCC screening; the combination of SCCA-IgM and AFP is the best diagnostic option.

Keywords: diagnostic accuracy; meta-analysis; screening for hepatocellular carcinoma; squamous cell carcinoma antigen.

Publication types

  • Meta-Analysis

MeSH terms

  • Antigen-Antibody Complex / blood*
  • Antigens, Neoplasm / blood*
  • Area Under Curve
  • Biomarkers, Tumor / blood
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / diagnosis*
  • Female
  • Humans
  • Immunoglobulin M / blood
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis*
  • Male
  • Odds Ratio
  • ROC Curve
  • Sensitivity and Specificity
  • Serpins / blood*
  • alpha-Fetoproteins / analysis


  • Antigen-Antibody Complex
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Immunoglobulin M
  • Serpins
  • alpha-Fetoproteins
  • squamous cell carcinoma-related antigen