Second malignant tumors in patients with nasopharyngeal carcinoma and their association with Epstein-Barr virus.

Since previous published studies about second malignant tumors (SMTs) in nasopharyngeal carcinoma (NPC) patients usually included a limited sample size and did not attain consistent results, we conducted a large retrospective study in a cohort of 1,549 patients to assess the risk of SMT in NPC patients following radiotherapy (RT) in Taiwan. The follow-up period ranged from 2 to 16 years, with a median of 7 years. Thirty-nine patients developed SMTs during the 7,145 person-year follow-up [standardized incidence ratio (SIR): 2. 8; 95% confidence interval (CI): 2.0 to 3.9]. Increased risks of developing SMTs were observed for head and neck (H/N) cancer (SIR: 16.5; 95% CI: 10.0 to 26.8), gastric cancer (SIR: 5.5; 95% CI: 2.2 to 11.4) and leukemia (SIR: 9; 95% CI: 1.9 to 26.3). Paraffin-embedded specimens of secondary H/N cancer (11), secondary gastric cancer (6) and their corresponding NPC specimens were examined by EBER in situ hybridization to assess the association between Epstein-Barr virus (EBV) and these SMTs. Twenty-six primary H/N and 5 gastric cancer specimens were chosen as the control groups. In H/N cancer, EBV was detected in 3.8% of the primary cancers and 9.1% of the secondary cancers. All the positive specimens resulted from hypopharyngeal cancer. Of the secondary gastric cancers, only 1 case (16.6%) was associated with EBV. None of the primary gastric cancers was associated with EBV. Our results indicate an increased risk of developing SMTs, with a preference for head and neck cancer, gastric cancer and leukemia, in NPC patients after RT in Taiwan. Only a small proportion of the secondary H/N and gastric cancers was associated with EBV.