Detection of circulating tumor HPV-DNA in patients with HPV-positive sinonasal and nasopharyngeal carcinoma

Authors

  • Jakob Myllerup Jensen Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital – Rigshospitalet, Denmark
  • Simone Kloch Bendtsen Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital – Rigshospitalet, Denmark
  • Kathrine Kronberg Jakobsen Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital – Rigshospitalet, Denmark
  • Katalin Kiss Department of Pathology, Copenhagen University Hospital – Rigshospitalet, Denmark
  • Maria Rossing MDxCORE, Department of Clinical Biochemistry, Copenhagen University Hospital – Rigshospitalet, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen
  • Christian Grønhøj Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital – Rigshospitalet, Denmark
  • Christian von Buchwald Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital – Rigshospitalet, Denmark

DOI:

https://doi.org/10.2340/1651-226X.2026.46393

Keywords:

HPV, ctHPV-DNA, biomarker, sinonasal carcinoma, nasopharyngeal carcinoma

Abstract

Background: Approximately 30% of sinonasal and nasopharyngeal carcinoma cases are HPV-associated, yet studies investigating circulating tumor HPV-DNA (ctHPV-DNA) among these patients are scarce. The aim of this study was to investigate the sensitivity of ctHPV-DNA in pretreatment blood samples from patients with HPV-positive (HPV+) sinonasal and nasopharyngeal carcinoma.

Methods: Patients with a confirmed HPV+ sinonasal or nasopharyngeal carcinoma treated at the Department of Otorhinolaryngology, Head and Neck Surgery and Audiology at Rigshospitalet, Copenhagen, Denmark in the period 2017–2025 were included in this study. Blood samples were drawn in Streck tubes before treatment initiation and analysed for the presence of ctHPV-DNA by Droplet digital PCR (ddPCR).

Results: Fifteen patients with primary HPV+ sinonasal or nasopharyngeal carcinoma were included. Except for two cases of HPV-related multiphenotypic carcinoma, all cases were squamous cell carcinoma. HPV16 was most prevalent and found in 6 patients (40%). HPV18 (n = 2), HPV33 (n = 1), HPV35 (n = 3), HPV45 (n = 1), and HPV56 (n = 2) were also represented. The sensitivity of detecting ctHPV-DNA in the pretreatment blood samples of the included patients was 80%. The level of ctHPV-DNA increased significantly with increasing T-category.

Conclusion: ctHPV-DNA was detected in pretreatment blood samples in 80% of patients with HPV+ sinonasal and nasopharyngeal carcinoma. This supports further investigation of ctHPV-DNA as a biomarker for post-treatment surveillance in these patients.

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References

Sjöstedt S, von Buchwald C, Agander TK, Aanaes K. Impact of human papillomavirus in sinonasal cancer – a systematic review. Acta Oncol. 2021;60:1175–91. DOI: https://doi.org/10.1080/0284186X.2021.1950922

Amanian A, Ishii M, Fakhry C, London NR. Epidemiologic trends in human papillomavirus–associated sinonasal squamous cell carcinoma. JAMA Otolaryngol. Head Neck Surg. 2024;150:609. DOI: https://doi.org/10.1001/jamaoto.2024.1311

Stenmark MH, McHugh JB, Schipper M, Walline MH, Komack C, Feng FY, et al. Nonendemic HPV-positive nasopharyngeal carcinoma: association with poor prognosis. Int J Radiat Oncol Biol Phys. 2024;88:580–8. DOI: https://doi.org/10.1016/j.ijrobp.2013.11.246

Wotman M, Oh EJ, Ahn S, Kraus D, Constantino P, Tham T. HPV status in patients with nasopharyngeal carcinoma in the United States: a SEER database study. Am J Otolaryngol Head Neck Med Surg. 2019;40:705–10. DOI: https://doi.org/10.1016/j.amjoto.2019.06.007

Pallisgaard N, Spindler KLG, Andersen RF, Brandslund I, Jakobsen A. Controls to validate plasma samples for cell free DNA quantification. Clin Chim Acta. 2015;446:141–6. DOI: https://doi.org/10.1016/j.cca.2015.04.015

Jakobsen KK, Bendtsen SK, Pallisgaard N, Friborg J, Lelkaitis G, Groenhoej C, et al. Liquid biopsies with circulating plasma HPV-DNA measurements – a clinically applicable surveillance tool for patients with HPV-positive oropharyngeal cancer. Clin Cancer Res. 2023;29:3914–23. DOI: https://doi.org/10.1158/1078-0432.CCR-23-1064

Naegele S, Efthymiou V, Das D, Sadow PM, Richmon JD, Iafrate AJ, et al. Detection and monitoring of circulating tumor HPV DNA in HPV-associated sinonasal and nasopharyngeal cancers. JAMA Otolaryngol Head Neck Surg. 2023;149:179–81. DOI: https://doi.org/10.1001/jamaoto.2022.4107

Adelman AE, Motwani K, Chapurin N. Circulating tumor DNA testing for detection and surveillance of sinonasal HPV-associated cancers. J Neurol Surg Rep. 2025;86:e89. DOI: https://doi.org/10.1055/a-2576-7496

Whitehead RA, Papagiannopoulos P, Joshi N, Bhayani MK. Identification and surveillance of unusual primary site using human papillomavirus-specific cell-free tumor DNA. Otolaryngol Head Neck Surg. 2024;171:1611–13. DOI: https://doi.org/10.1002/ohn.872

Spindler K-LG, Jakobsen AV, Eriksen JG, Fokdal L, Nordsmark M, Thorsen LBJ, et al. The clinical utility of circulating human papillomavirus across squamous cell carcinomas. Acta Oncol. 2025;64:1–12. DOI: https://doi.org/10.2340/1651-226X.2025.41288

Ferrandino RM, Chen S, Kappauf C, Barlow J, Gold BS, Berger MH, et al. Performance of liquid biopsy for diagnosis and surveillance of human papillomavirus-associated oropharyngeal cancer. JAMA Otolaryngol Head Neck Surg. 2023;149:971–7. DOI: https://doi.org/10.1001/jamaoto.2023.1937

Campo F, Paolini F, Terrenato I, Blandino G, Pascale VD, Iocca O, et al. Circulating HPVDNA in patients undergoing transoral robotic surgery for oropharyngeal cancer: liquid biopsy could identify molecular residual disease. Eur Arch Oto Rhino Laryngol. 2025;282:3193–9. DOI: https://doi.org/10.1007/s00405-025-09218-x

Lauritzen BB, Sjöstedt S, Jensen JM, Kiss K, von Buchwald C. Unusual cases of sinonasal malignancies: a letter to the editor on HPV-positive sinonasal squamous cell carcinomas. Acta Oncol. 2023;62:608–13. DOI: https://doi.org/10.1080/0284186X.2023.2224508

Zamuner FT, Gunti S, Starrett GJ, Faraji F, Toni T, Saraswathula A, et al. Molecular patterns and mechanisms of tumorigenesis in HPV-associated and HPV-independent sinonasal squamous cell carcinoma. Nat Commun. 2025;16(1):5285. DOI: https://doi.org/10.1038/s41467-025-59409-7

Published

2026-10-20

How to Cite

Myllerup Jensen, J., Kloch Bendtsen, S., Kronberg Jakobsen, K., Kiss, K., Rossing, M., Grønhøj, C., & von Buchwald, C. (2026). Detection of circulating tumor HPV-DNA in patients with HPV-positive sinonasal and nasopharyngeal carcinoma. Acta Oncologica, 65, 857–859. https://doi.org/10.2340/1651-226X.2026.46393