Undifferentiated Nasopharyngeal Carcinoma in Low- and Middle-Income Countries: Clinical, Molecular, and Health-System-Related Challenges

Undifferentiated nasopharyngeal carcinoma (UNPC) is a virally driven malignancy that disproportionately impacts low- and middle-income countries (LMICs). Although advances in MRI, intensity-modulated radiotherapy (IMRT), and plasma Epstein-Barr virus (EBV) DNA testing have substantially improved outcomes in well-resourced settings, significant diagnostic and therapeutic gaps remain across endemic LMIC regions. More than 70% of global UNPC cases occur in these settings, where delayed diagnosis, limited access to MRI and PET-CT, restricted availability of EBV DNA testing, and fragile radiotherapy capacity contribute to advanced-stage presentation and poorer survival. Molecular and proteomic analyses have identified clinically relevant UNPC subgroups, but their translation into routine care is constrained by inadequate laboratory infrastructure. Systemic therapy delivery is often compromised by drug shortages, logistical challenges, and financial barriers, while substantial psychosocial distress further undermines treatment adherence. UNPC outcomes reflect an interplay between tumor biology and broader health system inequities. Strengthening referral pathways, decentralizing diagnostic services, scaling EBV DNA testing, reinforcing radiotherapy infrastructure, and integrating supportive care represent feasible, high-impact strategies to reduce survival disparities in LMICs.