Epidemiology and treatment outcome of nasopharyngeal carcinoma in a low-incidence population – a DAHANCA analysis in Denmark 2000–2018

Authors

  • Erik Schiess Department of Oncology, Rigshospitalet, Denmark
  • Kristian H. Jensen Department of Oncology, Rigshospitalet, Denmark
  • Morten H. Kristensen Department of Oncology, Aarhus University Hospital, Denmark; Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark
  • Jørgen Johansen Department of Oncology, Odense University Hospital, Denmark
  • Jesper G. Eriksen Department of Oncology, Aarhus University Hospital, Denmark; Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark
  • Christian Maare Department of Oncology, University Hospital Herlev, Denmark
  • Maria Andersen Department of Oncology, Aalborg University Hospital, Denmark
  • Mohammad Farhadi Department of Oncology, Zealand University Hospital Naestved, Denmark
  • Christian R. Hansen Department of Oncology, Odense University Hospital, Denmark
  • Jens Overgaard Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark
  • Lisa L. Hjalgrim Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Denmark
  • Giedrius Lelkaitis Department of Pathology, Rigshospitalet, Denmark
  • Jeppe Friborg https://orcid.org/0000-0001-5423-0627

DOI:

https://doi.org/10.2340/1651-226X.2024.40499

Keywords:

Nasopharyngeal carcinoma, Radiotherapy, Epstein-Barr Virus, Head and neck cancer

Abstract

Introduction: Nasopharyngeal carcinoma (NPC) is a rare disease and most studies have therefore been conducted in endemic areas. The aim of this study was to describe epidemiology and treatment outcomes of NPC in a population-based, non-endemic setting.

Material and methods: Patients with NPC diagnosed in Denmark from 2000 to 2018 were identified in the Danish Head and Neck Cancer Study Group (DAHANCA) database. Clinical records were reviewed to obtain missing data and confirm outcome, histological subtypes, Epstein-Barr virus (EBV)-status, prognostic factors, and treatment.

Results: NPC was identified in 394 patients corresponding to age-standardized incidence rates of 0.5 and 0.2 per 100,000 in men and women, respectively. The 5-year overall (OS) and disease-specific survival (DSS) were 56 and 66%. In multivariate analysis, stage, smoking, and histology affected both OS and DSS, as patients with undifferentiated carcinomas had superior outcomes. Tumor EBV-status was determined in 221 patients, of whom 160 (72%) tested positive. EBV-positivity was associated with an improved OS in univariate analysis, but not after adjustment for relevant clinical factors.

Interpretation: NPC is a rare malignancy in Denmark, and three in four patients have EBV-associated tumors. Tumor histology, smoking status, and stage, but not EBV-status, had independent prognostic impact on survival.

Downloads

Download data is not yet available.

References

Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.

https://doi.org/10.1002/ijc.29210 DOI: https://doi.org/10.1002/ijc.29210

El-Naggar AK, Grandis JR, Takata T, et al. WHO classification of tumours, 4th edition, volume 9. WHO classification of head and neck tumours. WHO; 2017.

Chang ET, Ye W, Zeng YX, et al. The evolving epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2021;30(6):1035–47.

https://doi.org/10.1158/1055-9965.EPI-20-1702 DOI: https://doi.org/10.1158/1055-9965.EPI-20-1702

Chen YP, Chan ATC, Le QT, et al. Nasopharyngeal carcinoma. Lancet. 2019;394(10192):64–80.

https://doi.org/10.1016/S0140-6736(19)30956-0 DOI: https://doi.org/10.1016/S0140-6736(19)30956-0

Arnold M, Wildeman MA, Visser O, et al. Lower mortality from nasopharyngeal cancer in the Netherlands since 1970 with differential incidence trends in histopathology. Oral Oncol. 2013;49(3):237–43.

https://doi.org/10.1016/j.oraloncology.2012.09.016 DOI: https://doi.org/10.1016/j.oraloncology.2012.09.016

Ruuskanen M, Grenman R, Leivo I, et al. Outcome of nasopharyngeal carcinoma in Finland: a nationwide study. Acta Oncol. 2018;57(2):251–6.

https://doi.org/10.1080/0284186X.2017.1346378 DOI: https://doi.org/10.1080/0284186X.2017.1346378

Makitie A, Ruuskanen M, Bentzen J, et al. The management and survival outcomes of nasopharyngeal cancer in the Nordic countries. Acta Oncol. 2018;57(4):557–60.

https://doi.org/10.1080/0284186X.2017.1408961 DOI: https://doi.org/10.1080/0284186X.2017.1408961

Grønlund MP, Jakobsen KK, Mirian C, et al. Nasopharyngeal malignancies in Denmark diagnosed from 1980 to 2014. Oral Oncol. 2021;122:105583.

https://doi.org/10.1016/j.oraloncology.2021.105583 DOI: https://doi.org/10.1016/j.oraloncology.2021.105583

Overgaard J, Jovanovic A, Godballe C, et al. The Danish head and neck cancer database. Clin Epidemiol. 2016;8:491–6.

https://doi.org/10.2147/CLEP.S103591 DOI: https://doi.org/10.2147/CLEP.S103591

Gulley ML, Tang W. Laboratory assays for Epstein-Barr virus-related disease. J Mol Diagn. 2008;10(4):279–92.

https://doi.org/10.2353/jmoldx.2008.080023 DOI: https://doi.org/10.2353/jmoldx.2008.080023

Jensen K, Friborg J, Hansen CR, et al. The Danish head and neck cancer group (DAHANCA) 2020 radiotherapy guidelines. Radiother Oncol. 2020;151:149–51.

https://doi.org/10.1016/j.radonc.2020.07.037 DOI: https://doi.org/10.1016/j.radonc.2020.07.037

Overgaard J, Hansen HS, Overgaard M, et al. A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) protocol 5–85. Radiother Oncol. 1998;46(2):135–46.

https://doi.org/10.1016/S0167-8140(97)00220-X DOI: https://doi.org/10.1016/S0167-8140(97)00220-X

Pagh A, Vedtofte T, Lynggaard CD, et al. The value of routine follow-up after treatment for head and neck cancer. A national survey from DAHANCA. Acta Oncol. 2013;52(2):277–84.

https://doi.org/10.3109/0284186X.2012.741324 DOI: https://doi.org/10.3109/0284186X.2012.741324

Befolkningstal – Danmarks Statistik [Internet]. [cited 2022 May 25]. Available from: https://www.dst.dk/da/Statistik/emner/borgere/befolkning/befolkningstal

World (WHO 2000–2025) standard – standard populations – SEER datasets [Internet]. [cited 2022 May 25]. Available from: https://seer.cancer.gov/stdpopulations/world.who.html

Friborg J, Koch A, Wohlfarht J, et al. Cancer in Greenlandic Inuit 1973–1997: a cohort study. Int J Cancer. 2003;107(6):1017–22.

https://doi.org/10.1002/ijc.11502 DOI: https://doi.org/10.1002/ijc.11502

Zamani M, Grønhøj C, Jensen DH, et al. The current epidemic of HPV-associated oropharyngeal cancer: an 18-year Danish population-based study with 2,169 patients. Eur J Cancer. 2020;134:52–9.

https://doi.org/10.1016/j.ejca.2020.04.027 DOI: https://doi.org/10.1016/j.ejca.2020.04.027

Friborg JT, Yuan JM, Wang R, et al. A prospective study of tobacco and alcohol use as risk factors for pharyngeal carcinomas in Singapore Chinese. Cancer. 2007;109(6):1183–91.

https://doi.org/10.1002/cncr.22501 DOI: https://doi.org/10.1002/cncr.22501

Ruuskanen M, Irjala H, Minn H, et al. Epstein-Barr virus and human papillomaviruses as favorable prognostic factors in nasopharyngeal carcinoma: a nationwide study in Finland. Head Neck. 2019;41(2):349–57.

https://doi.org/10.1002/hed.25450 DOI: https://doi.org/10.1002/hed.25450

Vaughan TL, Shapiro JA, Burt RD, et al. Nasopharyngeal cancer in a low-risk population: defining risk factors by histological type. Cancer Epidemiol Biomarkers Prev. 1996;5(8):587–93.

Johansen LV, Mestre M, Overgaard J. Carcinoma of the nasopharynx: analysis of treatment results in 167 consecutively admitted patients. Head Neck. 1992;14(3):200–7.

https://doi.org/10.1002/hed.2880140307 DOI: https://doi.org/10.1002/hed.2880140307

Huang WY, Lin CL, Lin CY, et al. Survival outcome of patients with nasopharyngeal carcinoma: a nationwide analysis of 13 407 patients in Taiwan. Clin Otolaryngol. 2015;40(4):327–34.

https://doi.org/10.1111/coa.12371 DOI: https://doi.org/10.1111/coa.12371

Zhang LL, Xu F, Song D, et al. Development of a Nomogram model for treatment of nonmetastatic NPC. JAMA Netw Open. 2020;3(12):e2029882.

https://doi.org/10.1001/jamanetworkopen.2020.29882 DOI: https://doi.org/10.1001/jamanetworkopen.2020.29882

Bossi P, Chan AT, Licitra L, et al. Nasopharyngeal carcinoma: ESMO-EURACAN clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(4):452–65.

https://doi.org/10.1016/j.annonc.2020.12.007 DOI: https://doi.org/10.1016/j.annonc.2020.12.007

Blanchard P, Lee A, Marguet S, et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015;16(6):645–55.

https://doi.org/10.1016/S1470-2045(15)70126-9 DOI: https://doi.org/10.1016/S1470-2045(15)70126-9

Liu Y, Yang L, Zhang S, et al. The efficacy and safety of concurrent chemoradiotherapy with induction chemotherapy vs. concurrent chemoradiotherapy alone for locally advanced nasopharyngeal carcinoma: a systematic-review and meta-analysis. Transl Cancer Res. 2022;11(5):1207–18.

https://doi.org/10.21037/tcr-22-604 DOI: https://doi.org/10.21037/tcr-22-604

Svajdler M, Jr, Kaspirkova J, Mezencev R, et al. Human papillomavirus and Epstein-Barr virus in nasopharyngeal carcinoma in a non-endemic eastern European population. Neoplasma. 2016;63(1):107–14.

https://doi.org/10.4149/neo_2016_013 DOI: https://doi.org/10.4149/neo_2016_013

Chan KC, Lo YM. Circulating EBV DNA as a tumor marker for nasopharyngeal carcinoma. Semin Cancer Biol. 2002;12(6):489–96.

https://doi.org/10.1016/S1044579X02000913 DOI: https://doi.org/10.1016/S1044579X02000913

Trevisiol C, Gion M, Vaona A, et al. The appropriate use of circulating EBV-DNA in nasopharyngeal carcinoma: comprehensive clinical practice guidelines evaluation. Oral Oncol. 2021;114:105128.

https://doi.org/10.1016/j.oraloncology.2020.105128 DOI: https://doi.org/10.1016/j.oraloncology.2020.105128

Dogan S, Hedberg ML, Ferris RL, et al. Human papillomavirus and Epstein-Barr virus in nasopharyngeal carcinoma in a low-incidence population. Head Neck. 2014;36(4):511–16.

https://doi.org/10.1002/hed.23318 DOI: https://doi.org/10.1002/hed.23318

Stenmark MH, McHugh JB, Schipper M, et al. Nonendemic HPV-positive nasopharyngeal carcinoma: association with poor prognosis. Int J Radiat Oncol Biol Phys. 2014;88(3):580–8.

https://doi.org/10.1016/j.ijrobp.2013.11.246 DOI: https://doi.org/10.1016/j.ijrobp.2013.11.246

Downloads

Additional Files

Published

2024-11-04

How to Cite

Schiess, E., Jensen, K. H., Kristensen, M. H., Johansen, J., Eriksen, J. G., Maare, C. ., … Friborg, J. (2024). Epidemiology and treatment outcome of nasopharyngeal carcinoma in a low-incidence population – a DAHANCA analysis in Denmark 2000–2018. Acta Oncologica, 63(1), 850–857. https://doi.org/10.2340/1651-226X.2024.40499

Issue

Vol. 63 (2024): Acta Oncologica

Section

Original article

License

Copyright (c) 2023 Erik Schiess, Kristian H. Jensen, Morten H. Kristensen, Jørgen Johansen, Jesper G. Eriksen, Christian Maare, Maria Andersen, Mohammad Farhadi, Christian R. Hansen, Jens Overgaard, Lisa L. Hjalgrim, Giedrius Lelkaitis, Jeppe Friborg

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.