Universität zu Köln

Klasen, Charlotte ORCID: 0009-0009-3120-0439, Eckel, Hans N. C. ORCID: 0000-0002-6947-9836, Wuerdemann, Nora ORCID: 0000-0002-1092-689X, Böckelmann, Joseph, Knipper, Karl ORCID: 0009-0008-7133-3538, Suchan, Malte ORCID: 0009-0000-0134-8509, Sharaf, Kariem ORCID: 0000-0001-7799-4005, Sharma, Shachi Jenny ORCID: 0000-0002-2768-7936, Abing, Helen ORCID: 0000-0001-8453-842X, Charpentier, Arthur ORCID: 0000-0001-9636-7437, Esser, Julia ORCID: 0009-0002-3556-3738, Hansen, Kevin ORCID: 0000-0001-5028-0600, Mayer, Marcel ORCID: 0000-0001-9963-1109, Jansen, Louis ORCID: 0000-0003-0332-1099, Klußmann, Jens Peter ORCID: 0000-0002-8223-7954, Quaas, Alexander ORCID: 0000-0002-3537-6011 and Lyu, Su Ir ORCID: 0009-0002-4125-6048 (2025). Expression patterns of TROP2 and Nectin-4 in oropharyngeal squamous cell carcinoma in relation to HPV status: potential biomarkers for targeted therapy. Therapeutic Advances in Medical Oncology, 17. pp. 1-14. Sage. ISSN 1758-8359

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Abstract

Background: Patients with inoperable or metastatic oropharyngeal squamous cell carcinoma (OSCC) face limited therapeutic options. Nectin-4, an immunoglobulin-like transmembrane adhesion protein, and Trophoblast Surface Antigen 2 (TROP2), a transmembrane glycoprotein, have recently emerged as targets for antibody–drug conjugates (ADCs). Enfortumab Vedotin, an ADC targeting Nectin-4, has been approved for locally advanced or metastatic urothelial carcinoma, while sacituzumab govitecan, targeting TROP2, was approved for metastatic triple-negative breast cancer. Objectives: This study aimed to demonstrate expression rates of TROP2 and Nectin-4 in a representative cohort of human papillomavirus (HPV)-positive and HPV-negative OSCC and discuss the relevance of those markers as possible targets for ADCs. Design: A retrospective cohort study. Methods:We analyzed tissue samples from 226 OSCC patients treated at the University Hospital of Cologne between 2005 and 2020. The expression of Nectin-4 and TROP2 was assessed using immunohistochemistry, and the H-score method was applied to categorize expression levels into four groups: negative (0–10), low (11–100), moderate (101–200), and high (201–300). Results: TROP2 expression was positive in 96.5% of the samples, with 84.1% showing moderate to high expression (H-Score 101–300). A total of 38.8% of the cases expressed Nectin-4. Notably, patients with HPV-positive OSCC demonstrated significantly higher Nectin-4 expression compared to those with HPV-negative OSCC (p < 0.001). Conclusion: This study is one of the first to investigate the expression of Nectin-4 and TROP2 in a cohort of both HPV-positive and HPV-negative OSCC patients. Our results indicate that TROP2 is almost universally expressed in OSCC, while Nectin-4 expression is less frequent. TROP2 and Nectin-4 are promising therapeutic targets for OSCC, with Nectin-4 being particularly relevant for HPV-positive patients. Clinical trials are necessary to confirm the clinical relevance and efficacy of ADCs targeting TROP2 and Nectin-4 in OSCC treatment.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Klasen, Charlotte UNSPECIFIED https://orcid.org/0009-0009-3120-0439 UNSPECIFIED Eckel, Hans N. C. UNSPECIFIED https://orcid.org/0000-0002-6947-9836 UNSPECIFIED Wuerdemann, Nora UNSPECIFIED https://orcid.org/0000-0002-1092-689X UNSPECIFIED Böckelmann, Joseph UNSPECIFIED UNSPECIFIED UNSPECIFIED Knipper, Karl UNSPECIFIED https://orcid.org/0009-0008-7133-3538 UNSPECIFIED Suchan, Malte UNSPECIFIED https://orcid.org/0009-0000-0134-8509 UNSPECIFIED Sharaf, Kariem UNSPECIFIED https://orcid.org/0000-0001-7799-4005 UNSPECIFIED Sharma, Shachi Jenny UNSPECIFIED https://orcid.org/0000-0002-2768-7936 UNSPECIFIED Abing, Helen UNSPECIFIED https://orcid.org/0000-0001-8453-842X UNSPECIFIED Charpentier, Arthur UNSPECIFIED https://orcid.org/0000-0001-9636-7437 UNSPECIFIED Esser, Julia UNSPECIFIED https://orcid.org/0009-0002-3556-3738 UNSPECIFIED Hansen, Kevin UNSPECIFIED https://orcid.org/0000-0001-5028-0600 UNSPECIFIED Mayer, Marcel UNSPECIFIED https://orcid.org/0000-0001-9963-1109 UNSPECIFIED Jansen, Louis UNSPECIFIED https://orcid.org/0000-0003-0332-1099 UNSPECIFIED Klußmann, Jens Peter UNSPECIFIED https://orcid.org/0000-0002-8223-7954 UNSPECIFIED Quaas, Alexander UNSPECIFIED https://orcid.org/0000-0002-3537-6011 UNSPECIFIED Lyu, Su Ir UNSPECIFIED https://orcid.org/0009-0002-4125-6048 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-811727
Identification Number:	10.1177/17588359251361877
Journal or Publication Title:	Therapeutic Advances in Medical Oncology
Volume:	17
Page Range:	pp. 1-14
Number of Pages:	14
Date:	October 2025
Publisher:	Sage
ISSN:	1758-8359
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Chirurgie > Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Transplantationschirurgie Faculty of Medicine > Hals-Nasen-Ohrenheilkunde > Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde Faculty of Medicine > Innere Medizin > Klinik I für Innere Medizin - Hämatologie und Onkologie Faculty of Medicine > Pathologie und Neuropathologie > Institut für Pathologie Faculty of Medicine > Weitere > Centrum für integrierte Onkologie (CIO) Zentrum für Molekulare Medizin
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language antibody–drug conjugates ; enfortumab vedotin ; HPV ; Nectin-4 ; oropharyngeal carcinoma ; sacituzumab govitecan ; targeted therapy ; TROP2 English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81172