title: A nation-wide epidemiological study on the risk of developing second malignancies in patients with different histological subtypes of nasopharyngeal carcinoma.
abstract: OBJECTIVE
  Risk assessment of second head/neck and Epstein Barr Virus (EBV)-related malignancies in patients with different nasopharyngeal carcinoma (NPC) subtypes.
  
  
  METHODS
  This 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 X(2)-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.
  
  
  RESULTS
  Histologically 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.
  
  
  CONCLUSIONS
  NPCs 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.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, The Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: Ooft
authors.affiliation: Department of Pathology, Erasmus University Medical Center Rotterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Ipenburg
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Center Utrecht, The Netherlands; Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, The Netherlands.
authors.forename: W W
authors.initials: WW
authors.lastname: Braunius
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Center Utrecht, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Stegeman
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Center Utrecht, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Wegner
authors.affiliation: Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: de Bree
authors.affiliation: PALGA Foundation, Houten, The Netherlands.
authors.forename: L I H
authors.initials: LI
authors.lastname: Overbeek
authors.affiliation: Department of Pathology, Erasmus University Medical Center Rotterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Koljenović
authors.affiliation: Department of Pathology, University Medical Center Utrecht, The Netherlands. Electronic address: S.M.Willems-4@umcutrecht.nl.
authors.forename: S M
authors.initials: SM
authors.lastname: Willems
mesh_terms: D002277:Carcinoma; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000145:classification / Q000473:pathology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D012307:Risk Factors
keywords: Cancer registry; Database; EBV; Epidemiology; Epstein Barr Virus; Follow-up; Histology; Nasopharyngeal carcinoma; Netherlands; Second primary malignancy