A nation-wide epidemiological study on the risk of developing second malignancies in patients with different histological subtypes of nasopharyngeal carcinoma

• Patients with NPC have a higher risk of SPM regardless of EBV status.
• SPM are more prevalent in keratinizing NPC compared to non-keratinizing NPC.
• Clinical follow-up of NPC patients, with specific attention on SPM, is justified.

SummaryObjectiveRisk assessment of second head/neck and Epstein Barr Virus (EBV)-related malignancies in patients with different nasopharyngeal carcinoma (NPC) subtypes.MethodsThis is a cross-sectional study. Pathology records were retrieved from PALGA (a Dutch pathology registry database) between 1995 and 2013. Second primary malignancy (SPM) data was extracted from PALGA. Odds ratios (OR) for SPM in the head/neck, and the upper/lower airways were calculated using logistic regression. Pearson X2-test and Fisher’s exact test were used to assess the relationship between NPC (and EBV-status) with SPM. Standardized incidence rates (SIR) were calculated.ResultsHistologically diagnosed NPC (keratinizing and undifferentiated and differentiated non-keratinizing subtypes) (n = 1175) were identified. NPC patients have an increased risk of second head/neck malignancies (SIR 4.7 95% CI 3.3–6.5). Keratinizing NPCs have an OR of 1.947 (95% CI 1.362–2.782) for SPM, an OR of 4.026 (95% CI 2.308–7.023) for carcinomas of the upper/lower airways, an OR of 4.306 (95% CI 2.299–8.066) for head/neck malignancies, an OR of 5.289 (95% CI 2.740–10.211) for HNSCC with a SIR of 4.7 (95CI 3.3–6.5). Non-keratinizing NPCs also have an increased risk of head/neck malignancies with a SIR of 3.2 (95% CI 1.8–5.1), but less than keratinizing NPCs (p = <0.001). Positive EBV-status is not associated with (EBV-related) SPM.ConclusionNPCs have a higher risk of SPM regardless of EBV status. SPM (especially HNSCC and malignancies of the upper aerodigestive tract) are more prevalent in keratinizing NPC compared to non-keratinizing NPC. Close clinical follow-up of NPC patients, with specific attention on SPM, is justified.