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Discordance Between p16-Expression and HPV-Status in Sinonasal Carcinoma: A Multicenter Retrospective Study
by
, , ,
Nina Wenda
1,*,†
,
Henrike Barbara Zech
2,3,†,
Marta Barde
1,
Leoni Ramke
2,
Anna Sophie Hoffmann
2,
Till Clauditz
4,
Sebastian Wagner
5,
Jan Gosepath
1,‡ and
Christian Stephan Betz
2,‡ 1
Department of Otolaryngology, Head and Neck Surgery, Helios HSK Wiesbaden, 65199 Wiesbaden, Germany
2
Department of Otolaryngology, Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
3
Mildred-Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
4
Department of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
5
Department of Pathology, Helios HSK Wiesbaden, 65199 Wiesbaden, Germany
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
Cancers 2025, 17(19), 3135; https://doi.org/10.3390/cancers17193135
Submission received: 10 August 2025
/
Revised: 7 September 2025
/
Accepted: 15 September 2025
/
Published: 26 September 2025
(This article belongs to the Special Issue Human Papillomavirus (HPV) and Related Cancer)
Simple Summary
Human papillomavirus (HPV) infection is known to be a risk factor of head and neck and especially throat cancer. A protein called p16 is often used as a detection marker for HPV-associated cancer. It is unclear whether cancers in the nose and sinuses (called sinonasal squamous cell carcinoma or SNSCC) are affected through HPV, and whether p16 is a reliable test for HPV in this disease. This study looked at 111 patients with SNSCC, diagnosed in two centers in Germany between 2008 and 2024. Tumors were tested for p16 and for HPV DNA. We found that about 28% of the tumors had HPV, mostly types 16 and 33. But in about 30% of cases, the p16 test results did not match the actual HPV DNA findings. This mismatch varied depending on the sites. Our findings suggest that p16 is insufficient as a standalone marker for detecting HPV-association. Method standardization and more precise testing is needed in cancers of the nasal cavity and paranasal sinus to the understanding of the biology of these rare and difficult-to-treat tumors.
Abstract
Background/Objectives: Human papillomavirus (HPV) infection is a well-established risk factor for oropharyngeal squamous cell carcinoma (OPSCC), where p16 immunohistochemistry serves as a surrogate marker. However, the role of HPV in sinonasal squamous cell carcinoma (SNSCC) remains less defined, and the reliability of p16 as a standalone surrogate is under debate. This study aimed to assess the concordance between p16 expression and HPV-DNA status in SNSCC and characterize clinicopathologic features in HPV-associated cases. Methods: We retrospectively analyzed 111 SNSCC cases diagnosed between 2008 and 2024 at two German centers. p16 status was determined by immunohistochemistry using site-specific antibody protocols. HPV-DNA testing and genotyping were performed via PCR and reverse hybridization. Clinical and histopathological data were collected and compared between HPV-positive and -negative tumors. Results: HPV-DNA was detected in 31/111 cases (27.9%), with HPV16 and HPV33 (Site A) and HPV 16 and HPV18 (Site B) being the most frequent subtypes. Discordance between p16 and HPV-DNA status was observed in 29.7% of cases, with site-specific discordance rates of 44.6% and 14.5%. Patients with HPV-positive tumors were younger than their HPV-negative counterparts. Conclusions: Our findings underscore the limitations of p16 as a single surrogate marker for detecting HPV-associated sinonasal cancer. Future research on the role of HPV in sinonasal cancer should integrate complementary testing methods (like p16Ink4A immunohistochemistry and HPV DNA/mRNA analysis) and aim for test standardization.
Keywords:
sinonasal carcinoma; human papilloma virus; biomarker discordance; p16; HPV-PCR
