Background To investigate the prognostic implications of histology among nasopharyngeal carcinoma (NPC) using the data from a Chinese cohort and the Surveillance, Epidemiology, and End Results (SEER) database. Methods We included patients diagnosed with WHO II and III subtypes NPC from two independent cohorts (Xiamen [XM]-NPC cohort and SEER-NPC cohort). Results We identified 726 patients in the XM-NPC cohort and 1334 patients in the SEER cohort. In the XM-NPC cohort, 94 (12.9%) and 632 (87.1%) patients had WHO II and III subtypes, respectively. In the SEER-NPC cohort, 839 (62.9%) and 495 (37.1%) patients had WHO II and III subtypes, respectively. WHO II subtype patients had a higher smoking rate than the WHO III subtype (57.4% vs. 43.4%) in the XM-NPC cohort. There were no significant differences in age, gender, tumor stage, or nodal stage between the two subtypes in both cohorts. In the XM-NPC cohort, patients with the WHO II subtype had worse locoregional relapse-free survival (82.2% vs. 89.5%, p = 0.063), distant metastasis-free survival (72.4% vs. 85.9%, p = 0.028), disease-free survival (61.6% vs. 78.8%, p = 0.003), and overall survival (OS) (71.7% vs. 84.0%, p = 0.035) than those with WHO III subtype. In the SEER-NPC cohort, patients with the WHO II subtype had worse NPC-specific survival (81.1% vs. 89.4%, p < 0.001) and OS (71.6% vs. 78.8%, p < 0.001) than those with WHO III subtype. The multivariate analysis showed that histology was an independent prognostic factor associated with outcomes in both cohorts. Conclusions Our study demonstrates the significant influence of histological subtypes on outcomes in NPC among various populations, highlighting substantial disparities between the WHO II and WHO III subtypes.
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