Head and Neck Cancer Group

CLINICAL RESEARCH

Our group focuses on translational and clinical and research in head and neck cancers including head and neck squamous cell carcinoma (HNSCC) which accounts for around 90% of these tumor types. We also study rare malignancies including salivary gland, nasopharyngeal, and sinonasal cancers, and NUT carcinoma.

We have collaborated in the development of anti-PD1 therapies for patients with head and neck squamous cell carcinoma from early clinical trial to the pivotal study which led to the approval as 1st line in recurrent-metastatic HNSCC (KEYNOTE-048 study, Burtness et al. 2022). Our group was a key contributor to the study leading to the approval of perioperative anti‑PD‑1 in resectable HNSCC (Uppaluri R. et al 2025). This strong multidisciplinary involvement has laid the foundation for an expanded research line exploring innovative perioperative combination approaches.

We are committed to developing biomarkers of drug sensitivity or resistance to immunotherapy and evaluating novel combinations that might overcome primary or secondary resistance to anti-PD1 therapies.

In close collaboration with VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, we aim to identify and develop novel agents to treat patients with head and neck cancers, and improve patient outcomes through personalized medicine.

We are proud to have received a grant from the Spanish Association Against Cancer (AECC), supporting clinical studies in oncology (Ayuda Estudios Clínicos). This funding has enabled us to initiate the EORTC-sponsored study entitled: PROLoNg: Pembrolizumab and Radiotherapy for OLigometastatic squamous cell carcinoma of the head and Neck: a randomized phase III study, in Spain. Support received from AECC also allows us to conduct the translational part of this study, evaluating the VIGex gene expression signature developed in-house by VHIO (Hernando-Calvo et al. 2023), as well as other tissue-based and circulating tumor biomarkers.

Building on our interest in rare cancers, our group has initiated an ISCIII‑funded project in collaboration with the Growth Factors Group, to investigate the role of p95HER2 in malignant salivary gland cancers.Our Group Leader, Irene Braña, is an active member of several leading professional societies and associations in oncology. She serves as a member of the European Society for Medical Oncology (ESMO) Congress Head and Neck Cancer Track (since 2020), the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Group, Cancer Core Europe, the American Society of Clinical Oncology (ASCO), and the Spanish Group of Head and Neck Cancer Treatment (TTCC). Her expertise significantly contributes to shaping precision oncology in the field of head and neck cancer.

Irene Braña

Group Leader

Biosketch

Research Lines

Develop immune-based therapies for the treatment of head and neck cancers, and identify biomarkers of drug sensitivity or resistance.
Clinical development of novel therapies for head and neck squamous cell carcinomas as well as rare malignancies including salivary gland cancers, nasopharyngeal, sinonasal, and NUT carcinoma.
Multidisciplinary collaboration to develop window-of-opportunity, neoadjuvant, and adjuvant studies for head and neck cancer patients.
Molecular characterization of head and neck tumors for the personalized treatment of individual patients.

Team

Group Leader

Irene Braña

Medical Oncologists and Clinical Investigators

Ilaria Mascagni, Gaspar Molina, Katerin Rojas

Publications

Most relevant scientific publications:

Uppaluri R, Haddad RI, Tao Y, Le Tourneau C, Lee NY, Westra W, Chernock R, Tahara M, Harrington KJ, Klochikhin AL, Braña I, Vasconcelos Alves G, Hughes BGM, Oliva M, Pinto Figueiredo Lima I, Ueda T, Rutkowski T, Schroeder U, Mauz PS, Fuereder T, Laban S, Oridate N, Popovtzer A, Mach N, Korobko Y, Costa DA, Hooda-Nehra A, Rodriguez CP, Bell RB, Manschot C, Benjamin K, Gumuscu B, Adkins D; KEYNOTE-689 Investigators. Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer. N Engl J Med. 2025 Jul 3;393(1):37-50.
Forster M, Brana I, Pousa AL, Doger B, Roxburgh P, Bajaj P, Peguero J, Krebs M, Carcereny E, Patel G, Mueller C, Brignone C, Triebel F. Eftilagimod Alpha (Soluble LAG3 Protein) Combined with Pembrolizumab as Second-Line Therapy for Patients with Metastatic Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2024 Sep 3;30(17):3726-3734.

Harrington KJ, Burtness B, Greil R, Soulières D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Basté N, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Lin J, Gumuscu B, Swaby RF, Rischin D. Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. J Clin Oncol. 2023 Feb 1;41(4):790-802.
Hernando-Calvo A, Mirallas O, Marmolejo D, Saavedra O, Vieito M, Assaf Pastrana JD, Aguilar S, Bescós C, Lorente J, Giralt J, Benavente S, Temprana-Salvador J, Alberola M, Dienstmann R, Garralda E, Felip E, Villacampa G, Brana I. Nutritional status associates with immunotherapy clinical outcomes in recurrent or metastatic head and neck squamous cell carcinoma patients. Oral Oncol. 2023 May;140:106364.
Vieito M, Moreno V, Spreafico A, Brana I, Wang JS, Preis M, Hernández T, Genta S, Hansen AR, Doger B, Galvao V, Lenox L, Brown RJ, Kalota A, Mehta J, Pastore F, Patel B, Mistry P, Gu J, Lauring J, Patel MR. Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors. Clin Cancer Res. 2023 Sep 15;29(18):3592-3602.

All publications:

Uppaluri R, Haddad RI, Tao Y, Le Tourneau C, Lee NY, Westra W, Chernock R, Tahara M, Harrington KJ, Klochikhin AL, Braña I, Vasconcelos Alves G, Hughes BGM, Oliva M, Pinto Figueiredo Lima I, Ueda T, Rutkowski T, Schroeder U, Mauz PS, Fuereder T, Laban S, Oridate N, Popovtzer A, Mach N, Korobko Y, Costa DA, Hooda-Nehra A, Rodriguez CP, Bell RB, Manschot C, Benjamin K, Gumuscu B, Adkins D; KEYNOTE-689 Investigators. Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer. N Engl J Med. 2025 Jul 3;393(1):37-50. doi: 10.1056/NEJMoa2415434. Epub 2025 Jun 18. PMID: 40532178.
Tahara M, Greil R, Rischin D, Harrington KJ, Burtness B, de Castro G, Psyrri A, Braña I, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesía R, Ngamphaiboon N, Rordorf T, Ishak WZW, Lin J, Gumuscu B, Lerman N, Soulières D. Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up from the randomized phase III KEYNOTE-048 study. Eur J Cancer. 2025 May 15;221:115395. doi: 10.1016/j.ejca.2025.115395. Epub 2025 Apr 4. PMID: 40262400.
Even C, Harrington KJ, Massarelli E, Laban S, Fayette J, Oliva M, Klein Hesselink M, Visscher S, Fury MG, Wiekmeijer AS, Licitra L, Melichar B, Devriese LA, Braña I, Jankowska P, Posner M, Glisson B, Kong A, Hooftman L, Melief CJM MD,, Ferrarotto R. Randomized clinical efficacy and safety study of peltopepimut-S plus cemiplimab compared to cemiplimab alone in patients with recurrent/metastatic HPV16-positive head and neck cancer. J Immunother Cancer. 2025 Sep 8;13(9):e012555. doi: 10.1136/jitc-2025-012555. PMID: 40921630; PMCID: PMC12421166.
Jiménez-Labaig P, Aymerich C, Rullan A, Cacicedo J, Braña I, Nutting C, Newbold K, Harrington KJ, Catalan A. Prevalence of depressive and anxiety symptoms in patients with head and neck cancer undergoing radiotherapy: A systematic review and meta-analysis of longitudinal studies. Radiother Oncol. 2025 Jan;202:110649. doi: 10.1016/j.radonc.2024.110649. Epub 2024 Nov 24. PMID: 39586358.
Identification of Precise 3D CT Radiomics for Habitat Computation by Machine Learning in Cancer. Prior O, Macarro C, Navarro V, Monreal C, Ligero M, Garcia-Ruiz A, Serna G, Simonetti S, Braña I, Vieito M, Escobar M, Capdevila J, Byrne AT, Dienstmann R, Toledo R, Nuciforo P, Garralda E, Grussu F, Bernatowicz K, Perez-Lopez R. Radiol Artif Intell. 2024 Mar;6(2):e230118. doi: 10.1148/ryai.230118.
Intratumoral therapies in head and neck squamous cell carcinoma: A systematic review and future perspectives. Jiménez-Labaig P, Rullan A, Braña I, Hernando-Calvo A, Moreno V, Doger B, Bitar G, Ap Dafydd D, Melcher A, Harrington KJ. Cancer Treat Rev. 2024 Jun;127:102746. doi: 10.1016/j.ctrv.2024.102746.
A comprehensive examination of mental health in patients with head and neck cancer: systematic review and meta-analysis. Jimenez-Labaig P, Aymerich C, Braña I, Rullan A, Cacicedo J, González-Torres MÁ, Harrington KJ, Catalan A. JNCI Cancer Spectr. 2024 Apr 30;8(3):pkae031. doi: 10.1093/jncics/pkae031.
A systematic review of antibody-drug conjugates and bispecific antibodies in head and neck squamous cell carcinoma and nasopharyngeal carcinoma: Charting the course of future therapies. Jiménez-Labaig P, Rullan A, Hernando-Calvo A, Llop S, Bhide S, O’Leary B, Braña I, Harrington KJ. Cancer Treat Rev. 2024 Jul;128:102772. doi: 10.1016/j.ctrv.2024.102772.
Eftilagimod Alpha (Soluble LAG3 Protein) Combined with Pembrolizumab as Second-Line Therapy for Patients with Metastatic Head and Neck Squamous Cell Carcinoma. Forster M, Brana I, Pousa AL, Doger B, Roxburgh P, Bajaj P, Peguero J, Krebs M, Carcereny E, Patel G, Mueller C, Brignone C, Triebel F. Clin Cancer Res. 2024 Sep 3;30(17):3726-3734. doi: 10.1158/1078-0432.CCR-24-0473.
Pembrolizumab plus epacadostat in patients with recurrent/metastatic head and neck squamous cell carcinoma (KEYNOTE-669/ECHO-304): a phase 3, randomized, open-label study. Cho BC, Braña I, Cirauqui B, Aksoy S, Couture F, Hong RL, Miller WH Jr, Chaves-Conde M, Teixeira M, Leopold L, Munteanu M, Ge JY, Swaby RF, Hughes BGM. BMC Cancer. 2024 Jul 25;23(Suppl 1):1254. doi: 10.1186/s12885-023-11316-0.
Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. Leary A, Oaknin A, Trigo JM, Moreno V, Delord JP, Boni V, Braña I, Fernández C, Kahatt C, Nieto A, Cullell-Young M, Zeaiter A, Subbiah V. Eur J Cancer. 2023 Oct;192:113259. doi: 10.1016/j.ejca.2023.113259. Epub 2023 Jul 28. PMID: 37634282 Free article.
Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors. Vieito M, Moreno V, Spreafico A, Brana I, Wang JS, Preis M, Hernández T, Genta S, Hansen AR, Doger B, Galvao V, Lenox L, Brown RJ, Kalota A, Mehta J, Pastore F, Patel B, Mistry P, Gu J, Lauring J, Patel MR. Clin Cancer Res. 2023 Sep 15;29(18):3592-3602. doi: 10.1158/1078-0432.CCR-23-0092. PMID: 37491846.
Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors. Luke JJ, Fakih M, Schneider C, Chiorean EG, Bendell J, Kristeleit R, Kurzrock R, Blagden SP, Brana I, Goff LW, O’Hayer K, Geschwindt R, Smith M, Zhou F, Naing A. Br J Cancer. 2023 Jun;128(12):2227-2235. doi: 10.1038/s41416-023-02267-1. Epub 2023 Apr 22. PMID: 37087488.
Nutritional status associates with immunotherapy clinical outcomes in recurrent or metastatic head and neck squamous cell carcinoma patients. Hernando-Calvo A, Mirallas O, Marmolejo D, Saavedra O, Vieito M, Assaf Pastrana JD, Aguilar S, Bescós C, Lorente J, Giralt J, Benavente S, Temprana-Salvador J, Alberola M, Dienstmann R, Garralda E, Felip E, Villacampa G, Brana I. Oral Oncol. 2023 May;140:106364. doi: 10.1016/j.oraloncology.2023.106364. Epub 2023 Mar 28. PMID: 36989964.
BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas. Moreno V, Vieito M, Sepulveda JM, Galvao V, Hernández-Guerrero T, Doger B, Saavedra O, Carlo-Stella C, Michot JM, Italiano A, Magagnoli M, Carpio C, Pinto A, Sarmiento R, Amoroso B, Aronchik I, Filvaroff E, Hanna B, Wei X, Nikolova Z, Braña I. Nat Commun. 2023 Mar 13;14(1):1359. doi: 10.1038/s41467-023-36976-1. PMID: 36914652.
Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington KJ, Burtness B, Greil R, Soulières D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Basté N, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Lin J, Gumuscu B, Swaby RF, Rischin D. J Clin Oncol. 2023 Feb 1;41(4):790-802. doi: 10.1200/JCO.21.02508. Epub 2022 Oct 11. PMID: 36219809.

Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: A Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology. Pérez JMT, García-Cosío M, García-Castaño A, Gomà M, Mesia-Nin R, Ruiz-Bravo E, Soria-Rivas A, Castillo P, Braña-García I, Alberola-Ferranti M. Rev Esp Patol. 2023 Jan-Mar;56(1):45-57. doi: 10.1016/j.patol.2022.06.003. Epub 2022 Aug 27. PMID: 36599600.

Projects

PROLoNg: Pembrolizumab and Radiotherapy for OLigometastatic squamous cell carcinoma of the head and neck. Coordinator VHIO: Irene Braña. Funding entity: Estudios Clínicos AECC- NATIONAL CONSORTIUM..
Evaluación del rol de p95HER2 en la evolución de tumores malignos de glándula salival malignos y como posible diana terapéutica. Coordinator: Irene Brana. Funding entity: Instituto de Salud Carlos III.
tL-CHANCER: Unveiling the Role of T-Lymphocyte Clonal Hematopoiesis in Antitumor Immunity to Transform Cancer Immunotherapy. Coordinator: Francisco Martinez. Collaborator: Irene Brana.
Early clinical development of first-in-class EGL-001 targeting Tregs in head and neck squamous cell carcinoma, supported by AI-based pathomics – NEOTREG. Reference Number: 101290046. Co-Leads: Irene Braña & Fran Martínez. Funded by: European Commission. Execution Period: 01/06/2026-31/05/2031. VHIO

Irene Braña

Group Leader

Biosketch

Research Lines

Team

Group Leader

Irene Braña

Medical Oncologists and Clinical Investigators

Ilaria Mascagni, Gaspar Molina, Katerin Rojas

Publications

Projects

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