EMBO Molecular Medicine (Jul 2025)

LIMA1-alpha staining predicts curative intent surgery response in HPV negative head and neck cancer

  • Xi Qiao,
  • Johannes Routila,
  • Mari Tienhaara,
  • Heikki Irjala,
  • Priyadharshini Parimelazhagan Santhi,
  • Teemu Huusko,
  • Linda Nissi,
  • Ilkka Paatero,
  • Noora Lehtinen,
  • Juha Rantala,
  • Toni Viljanen,
  • Ilmo Leivo,
  • Petri Koivunen,
  • Anna Jouppila-Mättö,
  • Rami Taulu,
  • Leif Bäck,
  • Tommy Wilkman,
  • Eeva Haapio,
  • Ilpo Kinnunen,
  • Kari Kurppa,
  • Jukka Westermarck,
  • Sami Ventelä

DOI
https://doi.org/10.1038/s44321-025-00266-8
Journal volume & issue
Vol. 17, no. 8
pp. 2095 – 2114

Abstract

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Abstract In many solid cancer types, surgery alone could be a sufficient first therapy option for a significant number of cancer patients. However, there are currently no diagnostic solutions to identify patients who could be stratified to surgery alone. To identify a biomarker predicting cancer surgery response, candidate biomarkers were studied in a non-metastatic head and neck squamous cell carcinoma (nmHNSCC) cohort well representative of the HPV-negative patient population. LIMA1 immunohistochemistry (IHC) with specificity-validated antibodies outperformed all other biomarkers in multivariable survival analyses of patients with nmHNSCC (n = 128, HR 2.10, P = 0.006). The prognostic effect was selective to LIMA1-alpha isoform IHC detection in patients who had received surgical therapy (n = 184, HR 2.39, P > 0.001). Strikingly, our real-world validation results, using two prospectively collected cohorts (n = 15 and n = 86), demonstrate that none of the LIMA1 negative patients died of HNSCC during the follow-up. Collectively, we report here the discovery of a diagnostic LIMA1-alpha IHC assay for HPV-negative HNSCC patient stratification to surgery-only therapy. Application of LIMA1 detection in routine nmHNSCC diagnostics would revolutionize the clinical management of HNSCC patients.

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