The Cytidine Deaminase-Dependent and Independent Effects of APOBEC3A in Head and Neck Squamous Cell Carcinoma: A Literature Review

Abstract

Introduction: Head and neck squamous cell carcinoma (HNSCC) is a prevalent and aggressive cancer affecting mucosal linings, with increasing incidence in younger populations. Risk factors include tobacco, alcohol, and human papillomavirus (HPV) infection. Current treatments often result in significant side effects and limited success in preventing recurrence and metastasis. This study investigates the role of APOBEC3A, a cytidine deaminase, in HNSCC tumorigenesis, focusing on both deaminase-dependent and independent mechanisms.

Methods: A systematic literature review was conducted, searching PubMed, Web of Science, Embase, and Cochrane Library databases for relevant studies published between 2013 and 2024. Key terms included "APOBEC3A," "cytidine deaminase," "cancer," and "oncogenesis." Articles involving experimental studies with human tumor samples, in vitro and in vivo models, and clinical studies were included. Data were extracted on study design, methods, and findings related to APOBEC3A's role in HNSCC.

Results: APOBEC3A contributes to HNSCC through deaminase-dependent mechanisms, inducing C-to-T and C-to-G mutations, particularly in TP53 and PIK3CA genes, which are associated with tumor progression and resistance to therapies. Additionally, APOBEC3A's interaction with HPV further exacerbates genetic instability, leading to more aggressive tumor behavior. Deaminase-independent roles include modulation of the tumor microenvironment, influencing immune cell interactions and promoting immune evasion through cytokine production and PD-L1 expression.

Discussion: APOBEC3A's dual roles in HNSCC highlight its significance in both promoting oncogenic mutations and modulating immune responses. The enzyme's activity not only contributes to tumorigenesis through direct genetic alterations but also indirectly by creating a favorable environment for tumor growth and survival.

Conclusion: This study underscores the critical role of APOBEC3A in the pathogenesis of HNSCC and the need for targeted therapies addressing both its enzymatic and non-enzymatic functions. Future research should explore therapeutic strategies that inhibit APOBEC3A's activity and counteract its contributions to immune evasion and tumor progression.