Nasopharyngeal carcinomas (NPC) are non-endemic in most parts of India except in the northeastern region. We aimed to evaluate the use of estimation of plasma EBV (Epstein Bar Virus) DNA copy numbers on epidemiology and its impact on survival in NPC at a tertiary cancer center in India. In this ambispective study, we included treatment naïve biopsy-proven NPC treated at our institute between December 2013 and March 2023. Estimation of plasma EBV DNA was done at baseline, and at first follow-up, 3 months post-treatment completion. Plasma EBV analysis was done using the EBNA probe (n= 240) till September 2019 and the BAMH1 (n= 76) probe thereafter. The endpoints estimated were baseline EBV positivity rates, response rates based on EBV positivity/EBV copy numbers, and correlation of EBV positivity/EBV copy numbers with clinicoradiologic stage, FDG-PETCT parameters, and survival endpoints: Loco-regional Control (LRC), Distant Control (DC), Event Free Survival (EFS) and Overall Survival (OS). The study was approved by the Institutional Ethics Committee. Three hundred and sixteen patients were accrued in the study. The median age of patients was 43 (IQR: 28-54) years, and the majority were males (n=222, 70.3%). Sixty-two (19.6%) patients were from Endemic (Northeast India) regions out of which only 24 (36.1%) were plasma EBV positive. The most common histology was non-keratinizing or undifferentiated (WHO Types IIA & B) {n=248, (78.5%)}. T1/T2 and T3/T4 were equally distributed among the entire cohort (n=158, 50%) and N2/N3 (n=234, 74.1%) was the most common nodal classification. Metastatic disease (M1) was present in 25 (7.9%) patients. Most of the patients had stage III (n=105, 33.2%) or stage IV (n=169, 53.5%) disease. One hundred and seventeen (37%) patients were EBV-positive at baseline {n=82, (34.1%) with EBNA and n=35, (46.1%) with BAM H1}. Tissue diagnosis by IHC was available for 91 out of these patients. Out of these, there was a discordance in EBV status between EBV status by DNA copy number and tissue diagnosis in 36 (39.6%). The median copy numbers in those with detectable EBV (EBV positive) with EBNA was 712 copies/ml (IQR:332-1989), and BAM H1 was 425 copies/ml (IQR:162-1210). A high baseline EBV DNA copy number with BAMH1 (but not EBNA) was associated with a higher T stage (p=0.02). At the first follow-up, 283 (89.5%) patients had a complete response, and 33 (10.5%) patients had residual disease. Higher baseline EBV DNA copy numbers with BAMH1 (but not EBNA) correlated with an inferior complete response rate at the first follow-up (p=0.05). The median follow-up was 63.2 (IQR:33.5–87.4) months. At the last follow-up, 90 patients had failed, 27 (30%) locoregional (LR), 45 (50%) distant, and 18 (20%) combined locoregional and distant relapses. The 5-year LRC, DC, EFS, and OS for the entire cohort were 83.2% (95%CI:78.4-88), 77.5% (95% CI:72.3-82.7), 68.2% (95%CI: 62.6-73.8), 74.5 (95% CI:68.9-80.1). There was no significant difference in LRC, DC, EFS, and OS rates based on the overall EBV positivity vs negativity at baseline. None of the survival outcomes correlated with EBV positivity or EBV DNA copy number using the EBNA probe. The median follow-up of patients with BAMH1 probe analysis was 21 (IQR:13.1-33.5) months. There was no difference in survival outcomes based on EBV positivity vs negativity with the BAMH1 probe. However, in the patients with detectable EBV DNA with BAMH1, a higher DNA copy number/ml was associated with an inferior EFS (p=0.05). A cut-off value of 335 copies/ml (BAMH1) was most sensitive for predicting an inferior EFS. EBV positivity remained low in this nonendemic NPC population with both EBNA and BAMH1 probes, even amongst patients from the northeast. Hence, EBV DNA estimation cannot be routinely used as a screening, predictive, or prognostic marker uniformly for NPC patients in India. However, in those patients who have measurable EBV DNA copies, we found that the BAMH1 probe assay at baseline has a better predictive and prognostic value than the EBNA probe. The BAM H1 DNA copy number values may be incorporated as a baseline evaluation tool into routine clinical practice for further validation as a treatment decision aid in NPC in nonendemic regions. However, we would also like to further strengthen this estimation in a larger number of patients.