CD44 Expression in Head and Neck Cancer: Systematic Review, IHC-based Meta-Analysis, and Pathway Analysis Highlight a Favorable Clinicopathological Association

Marleen, Stella; Cangara, Muhammad Husni; Miskad, Upik Anderiani; Prihantono, Prihantono

doi:10.31557/APJCP.2026.27.9.3497

CD44 Expression in Head and Neck Cancer: Systematic Review, IHC-based Meta-Analysis, and Pathway Analysis Highlight a Favorable Clinicopathological Association

Document Type : Systematic Review and Meta-analysis

Authors

¹ Faculty of Medicine, Universitas Pelita Harapan, Indonesia.

² Department of Anatomical Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.

³ Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.

10.31557/APJCP.2026.27.9.3497

Abstract

Background: Head and neck cancer (HNC) is the seventh most common cancer worldwide with its highest incidence in Asia. Tobacco, alcohol, and HPV contribute to this phenomenon. CD44 has been found to have a mechanistic role in tumorigenicity and metastasis, however current literature shows conflicting evidence regarding its role in HNC. This review attempts to synthesize available studies to clarify its clinicopathological significance. Methods: A PRISMA-compliant systematic search was performed using PubMed, Cochrane, and the Directory of Open Access Journals for studies comparing clinicopathological features between immunohistochemically assessed CD44 expression levels. Meta-analysis was conducted utilizing Review Manager 5.4. Further subgroup analysis was conducted based on the CD44 expression quantification method. Results: Nine studies, representing 484 patients, were included in the final analysis. An association between CD44 expression and histopathological grading (OR = 0.46, 95% CI: 0.25–0.84) was found. Gender, survival, lymph node involvement, and perineural invasion were not found to be predicted by CD44. Conclusions: This meta-analysis demonstrates that CD44 expression is associated with histopathological grading in HNC. However, survival, lymph node involvement, and perineural invasion are found to be independent of CD44 expression.

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