Objectives: This review aims to provide a comprehensive comparative analysis of current treatment strategies for HN‑BL, evaluate their effectiveness and toxicity profiles, and highlight key clinical challenges that influence therapeutic decision‑making.

Methods: A systematic review of available literature on the treatment of head and neck Burkitt’s lymphoma was conducted, focusing on intensive chemotherapy regimens, radiation therapy roles, and novel targeted therapies. Treatment modalities were compared in terms of clinical outcomes, adverse effects, and patient functional status considerations.

Results: Intensive multi‑agent chemotherapy remains the cornerstone of HN‑BL management, often incorporating CNS prophylaxis due to the high risk of dissemination. The addition of targeted agents such as anti‑CD20 therapies has improved outcomes in select populations. Radiation therapy is generally limited to cases with residual disease or local control issues. Treatment choice is influenced by disease stage, performance status, and comorbidities. Major hurdles include managing treatment‑related toxicities, securing optimal local control, and addressing anatomical constraints inherent to head and neck involvement.

Conclusion: Effective therapy for HN‑BL requires an individualized, multidisciplinary approach. Current evidence supports aggressive chemotherapy as the primary modality, with emerging targeted therapies showing promise. Further research is needed to refine strategies that minimize toxicity while maximizing survival and functional outcomes. These insights could inform future clinical protocols and optimize patient care.

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