Matching Primary Tumor and Blood Gene Expression Analysis of HPV-negative Squamous Head and Neck Cancers (BIOMATCH)

Matching Primary Tumor and Blood Gene Expression Analysis of HPV-negative Squamous Head and Neck Cancers (BIOMATCH - Head and Neck)

The goal of this observational study is to learn whether a blood test can show the same biological features as the tumor in people with head and neck cancer that is not caused by HPV. These cancers often have different biological types, and these types may help predict how the cancer will behave. Today, these types can only be found by studying tumor tissue. This study wants to see if a simple blood sample can give the same information.

The main questions the study aims to answer are:

• Can a blood test identify the same tumor type that researchers find by studying tumor tissue under a microscope and through genetic testing?
• Can these blood test results help predict how people may do after finishing treatment?

Researchers will not assign treatments. All participants will receive the treatments recommended by their own care team as part of routine care.

Participants will:

• Give a blood sample before starting treatment.
• Give another blood sample about 3 months after finishing treatment.
• Allow researchers to use a sample of their tumor (already collected as part of standard care) for genetic testing.
• Continue routine follow-up visits with their care team.

About 300 adults with locally advanced, HPV-negative head and neck cancer (affecting the mouth, throat, voice box, or hypopharynx) will take part. Only people who are receiving treatment to cure their cancer can join. People with returning cancer or cancer that has already spread cannot join.

Researchers will study:

• Gene activity in tumor tissue
• Gene activity in blood
• Patterns in blood fragments and small molecules
• Digital images of tumor samples using computer-based tools

The study will compare these different types of information to see whether a blood test can reliably show the tumor's biological type. If it can, this could make it easier to monitor the cancer after treatment and may help guide future care.

This study does not test any new drug or treatment. It collects information that may help improve care for people with HPV-negative head and neck cancer in the future.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck (HNSCC)
• Intervention / Treatment: Other: Standard of Care (Investigator Choice)

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Lisa Licitra; Phone Number: +39 02 2390 2810; Email: lisa.licitra@istitutotumori.mi.it
• Study Contact Backup: Name: Stefano Cavalieri; Email: stefano.cavalieri@istitutotumori.mi.it

Study Locations

• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Contact: Lisa Licitra; Phone Number: +39 02 2390 2810; Email: lisa.licitra@istitutotumori.mi.it
  • Sassari, Italy
    • Recruiting
    • Azienda Ospedaliera Universitaria di Sassari
    • Contact: Francesco Bussu; Phone Number: +39 079 264 4509; Email: fbussu@uniss.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Loco-regionally advanced HPV-unrelated HNSCC adult patients amenable to treatments with curative intent.

Description

Inclusion Criteria:

• Pathologic diagnosis of HNSCC
• Primary HNSCC arising from the following sites of head and neck: oral cavity, p16-negative oropharynx, hypopharynx, larynx
• Stage III-IVa/b according to the eighth edition of AJCC/UICC classification
• Treatment with curative intent
• Unequivocal clinical and/or radiological absence of metastatic disease
• Patient ability and availability to comply with study protocol procedures.-

Exclusion Criteria:

• Recurrent/metastatic HNSCC
• p16+ oropharyngeal squamous cell carcinoma
• Evidence of high-risk HPV infection at tumor level
• Cancer of unknown primary site
• Non-squamous head and neck cancers (e.g., lymphoma, sarcoma, melanoma, salivary gland cancers)
• Skin squamous cell carcinoma from the skin of the head and neck
• Nasopharyngeal carcinoma
• Sinonasal/paranasal cancers
• Insufficient data about previous medical history.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of a blood profile (b-OMICS) in identifying the tumor tissue subtypes (t-OMICS) in loco-regionally advanced HPV-negative HNSCC patients.	AUROC (area under receiver operating characteristics) of b-OMICS (newly identified and developed in the current project) in diagnosing Cl2-Cl3 on t-OMICS (based on the transcriptomic model developed by De Cecco et al. Oncotarget 2015) in stage III-IVa/b (AJCC/UICC eighth edition) HPV-negative HNSCC patients treated with curative intent.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS of HPV-negative HNSCC patients based on their t-OMICS and b-OMICS.	Overall survival (OS) stratified according to t-OMICS (Cl2-Cl3 vs. others; presence or absence of b-OMICS signature).	6 months
DFS of HPV-negative HNSCC patients based on their t-OMICS and b-OMICS.	Disease-free survival (DFS) stratified according to t-OMICS (Cl2-Cl3 vs. others; presence or absence of b-OMICS signature).	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of a blood GE profile (b-OMICS) in identifying the digital pathology model in loco-regionally advanced HPV-negative HNSCC patients	Sensitivity of b-OMICS (newly identified and developed in the current project) in diagnosing the digital pathology model (newly identified and developed in the current project) in stage III-IVa/b (AJCC/UICC eighth edition) HPV-negative HNSCC patients treated with curative intent	6 months
Specificity of a blood GE profile (b-OMICS) in identifying the digital pathology model in loco-regionally advanced HPV-negative HNSCC patients	Specificity of b-OMICS (newly identified and developed in the current project) in diagnosing the digital pathology model (newly identified and developed in the current project) in stage III-IVa/b (AJCC/UICC eighth edition) HPV-negative HNSCC patients treated with curative intent	6 months
Sensitivity of a digital pathology model in identifying the t-OMICS in loco-regionally advanced HPV-negative HNSCC patients	Sensitivity of digital pathology model (newly identified and developed in the current project) in diagnosing Cl2-Cl3 on t-OMICS (based on the transcriptomic model developed by De Cecco et al. Oncotarget 2015) in stage III-IVa/b (AJCC/UICC eighth edition) HPV-negative HNSCC patients treated with curative intent	6 months
Specificity of a digital pathology model in identifying the t-OMICS in loco-regionally advanced HPV-negative HNSCC patients	Specificity of digital pathology model (newly identified and developed in the current project) in diagnosing Cl2-Cl3 on t-OMICS (based on the transcriptomic model developed by De Cecco et al. Oncotarget 2015) in stage III-IVa/b (AJCC/UICC eighth edition) HPV-negative HNSCC patients treated with curative intent	6 months
DFS of HPV-negative HNSCC patients based on digital pathology model.	DFS stratified according to the newly developed digital pathology model.	6 months
OS of HPV-negative HNSCC patients based on digital pathology model.	OS stratified according to the newly developed digital pathology model.	6 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Collaborators: Fondazione Policlinico Universitario Agostino Gemelli IRCCS; San Raffaele University Hospital, Italy; Istituto Europeo di Oncologia; Azienda Ospedaliero Universitaria di Sassari; Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale; Pineta Grande Hospital, Castel Volturno (CE), Italy
• Investigators: Principal Investigator: Lisa Licitra, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: April 2, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: INT137-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No