Oropharynx Squamous Cell CarcinomaCIRCOSNCT05904327
Circulating Biomarkers in Oropharyngeal Cancers
An observational study of Oropharynx Squamous Cell Carcinoma and Oropharynx Cancer, run by Region Örebro County at 1 site in Sweden.
Trial summary
The goal of this observational longitudinal study is to learn about circulating tumor Human Papilloma Virus-DNA (ctHPV-DNA) as a biomarker for HPV positive oropharyngeal cancer and cancer of unknown primary of the head and neck. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Oropharynx Squamous Cell Carcinoma, Oropharynx Cancer, Tonsillar Cancer
- How many people
- 130 participants
- Where
- 1 siteSweden
- Study dates
- 1 Dec 2020to 31 Mar 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Study participants are recruited from multidisciplinary conferences of head and neck cancer at Örebro University hospital - Region Örebro County, Västmanland's hospital - Region Västmanland and Karolinska University hospital - Region Stockholm. Örebro University hospital is a tertiary referral hospital of three regions in central Sweden (Region Värmland, Region Sörmland and Region Dalarna) and therefore patients from these regions will also be included in this study. All patients with OPSCC at any of the study centers will be asked to participate in CIRCOS. All study participants will sign an informed written consent upon inclusion
Who may be able to join
- Oropharyngeal cancer
- Cancer of unknown primary in the head and neck
Who cannot join
- Previous treatment of cancer in the oropharynx.
- Previous treatment of unknown primary tumor.
- Remote metastases
- Patients unwilling or unable to comply with the study protocol and follow-up schedule
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Use of Circulating Biomarkers in Oropharyngeal Cancer and Unknown Primary of Head and Neck - a Prospective Multicenter Study for Treatment Evaluation and Surveillance
The goal of this observational longitudinal study is to learn about circulating tumor Human Papilloma Virus-DNA (ctHPV-DNA) as a biomarker for HPV positive oropharyngeal cancer and cancer of unknown primary of the head and neck. The main questions it aims to answer are:
- Can ctHPV-DNA be used for treatment evaluation in HPV positive oropharyngeal cancer and cancer of unknown primary of the head and neck?
- Can circulating HPV-DNA be used as a biomarker for recurrent disease during surveillance?
Participants will be asked to leave plasma samples at diagnose, at the end of treatment and at every clinical follow-up.
The patients are there own controls.
Read the detailed description
In the multicenter study of CIRCOS, Circulating biomarkers in oropharyngeal cancer, patients with oropharyngeal cancer or cancer of unknown primary of the head and neck are consecutively included. Plasma samples are collected at diagnosis, at the end of treatment and during surveillance after treatment.
At diagnose participants will fill in informed consent and a form regarding known risk factors for cancer. Tissue from the tumor will be analyzed for HPV genotype with a multiplex q-PCR. Information about p16 will be collected from medical records.
ctHPV-DNA are short DNA fragments that leaks into the blood stream from tumor cells during apoptosis and necrosis. In the study, ctHPV-DNA will be extracted from blood plasma. Levels of ctHPV-DNA (copies/mL) will be measured using digital droplet PCR (ddPCR) with genotype specific assays (based on the result of q-PCR at diagnose) used in singleplex (SAGA diagnostics). A negative sample after treatment will be defined as a good molecular response for evaluation after treatment. Two consecutive, positive samples during surveillance will be defined as molecular recurrence. If a molecular recurrence is seen patients will be contacted and offered an extra clinical control at an Ear nose and throat department.
If a patient is HPV negative in tissue, the tissue will be analyzed with whole genome sequencing. If a mutation is found, a personalized ddPCR-kit will be used for plasma.
All patients will be followed for five years.
- Conditions
- Oropharynx Squamous Cell Carcinoma, Oropharynx Cancer, Tonsillar Cancer, Base of the Tongue Carcinoma
- Keywords
- circulating tumor DNA, HPV, human papilloma virus
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Oropharyngeal Neoplasms, Tonsillar Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
The accuracy of ctHPV-DNA as a biomarker for recurrent disease, measured in PPV and NPV
ctHPV-DNA will be evaluated by ddPCR. Two consecutive positive values will be defined as a molecular recurrance. The accuracy of the test will be presented with negative predictive value (NPV) and positive predictive value (PPV) at one, two (interim analysis) and at five year follow-up
Measured: 5 year follow-up
Secondary outcomes (2)
The correlation between molecular tumor burden (copies/mL) and radiological tumor burden (diameter and volume) using Kendall rank correlation coefficient.
Correlation of ctHPV-DNA and radiologic tumor burden at diagnosis and post treatment. ctHPV-DNA will be evaluated by ddPCR (copies/mL) at diagnose and at the end of treatment. The levels of ctHPV-DNA will be used as a measure of molecular tumor burden. The molecular tumor burden will be compared with the radiologic tumor burden, measured in diameter and volume in the diagnostic and evaluation computed tomography. The correlation will be calculated using Kendall rank correlation coefficient
Measured: 3 months follow-up
A comparison between molecular (copies/mL) and radiological response to treatment according to RECIST (Response Evaluation Criteria in Solid Tumors) using Kruskal wallis test.
The kinetics in ctHPV-DNA and will be compared to radiological confirmed treatment response in order to test ctHPV-DNA as a biomarker for treatment response. Radiological response will be evaluated according to the RECIST-criteria. Kinetics of ctHPV-DNA will be described as percentage change between pre- and post-treatment levels of ctHPV-DNA.
Measured: 3 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2023
- Study start1 Dec 2020
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Oropharynx Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Region Örebro County
- Sponsor type
- University, hospital or other
- Collaborators
- Region Stockholm, Region Västmanland, Dalarna County Council, Sweden, Sormland County Council, Sweden, Värmland County Council, Sweden
- Responsible party
- Sponsor
- Investigators
- Gisela Helenius, Study director, Örebro University, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05904327
- Sponsor's protocol ID
- 278627
- Acronym
- CIRCOS
- Status last verified
- Apr 2023
- First submitted
- 17 Apr 2023
- Last updated
- 15 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Almeren AO, Waenerlund M, Landstrom F, von Beckerath M, Qvick A, Carlsson J, Helenius G. Circulating Tumour DNA as a Complementary Tool for Treatment Evaluation in HPV-Associated Head and Neck Squamous Cell Carcinoma: An Observational Cohort Study. Clin Otolaryngol. 2025 Sep;50(5):831-839. doi: 10.1111/coa.14317. Epub 2025 Apr 22.
PubMed 40260766Qvick A, Andersson E, Oldaeus Almeren A, Waenerlund M, Stenmark B, Karlsson C, Karlsson MG, Helenius G. Sensitive and Specific Droplet Digital PCR Assays for Circulating Tumor HPV DNA: Development, Validation, and Clinical Application in HPV-Associated Cancers. Mol Diagn Ther. 2024 Nov;28(6):835-845. doi: 10.1007/s40291-024-00743-9. Epub 2024 Sep 26.
PubMed 39325260
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Circulating Biomarkers in Oropharyngeal Cancer and Unknown Primary of Head and Neck - a Prospective Multicenter Study for Treatment Evaluation and Surveillance
- ClinicalTrials.gov ID
- NCT05904327
- Acronym / sponsor ID
- CIRCOS / 278627
- Conditions
- Oropharynx Squamous Cell Carcinoma, Oropharynx Cancer, Tonsillar Cancer, Base of the Tongue Carcinoma
- Keywords
- circulating tumor DNA, HPV, human papilloma virus
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Region Örebro CountyUniversity, hospital or other
- Collaborators
- Region Stockholm, Region Västmanland, Dalarna County Council, Sweden, Sormland County Council, Sweden, Värmland County Council, Sweden
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 15 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this observational longitudinal study is to learn about circulating tumor Human Papilloma Virus-DNA (ctHPV-DNA) as a biomarker for HPV positive oropharyngeal cancer and cancer of unknown primary of the head and neck. The main questions it aims to answer are:
- Can ctHPV-DNA be used for treatment evaluation in HPV positive oropharyngeal cancer and cancer of unknown primary of the head and neck?
- Can circulating HPV-DNA be used as a biomarker for recurrent disease during surveillance?
Participants will be asked to leave plasma samples at diagnose, at the end of treatment and at every clinical follow-up.
The patients are there own controls.
Detailed description
In the multicenter study of CIRCOS, Circulating biomarkers in oropharyngeal cancer, patients with oropharyngeal cancer or cancer of unknown primary of the head and neck are consecutively included. Plasma samples are collected at diagnosis, at the end of treatment and during surveillance after treatment.
At diagnose participants will fill in informed consent and a form regarding known risk factors for cancer. Tissue from the tumor will be analyzed for HPV genotype with a multiplex q-PCR. Information about p16 will be collected from medical records.
ctHPV-DNA are short DNA fragments that leaks into the blood stream from tumor cells during apoptosis and necrosis. In the study, ctHPV-DNA will be extracted from blood plasma. Levels of ctHPV-DNA (copies/mL) will be measured using digital droplet PCR (ddPCR) with genotype specific assays (based on the result of q-PCR at diagnose) used in singleplex (SAGA diagnostics). A negative sample after treatment will be defined as a good molecular response for evaluation after treatment. Two consecutive, positive samples during surveillance will be defined as molecular recurrence. If a molecular recurrence is seen patients will be contacted and offered an extra clinical control at an Ear nose and throat department.
If a patient is HPV negative in tissue, the tissue will be analyzed with whole genome sequencing. If a mutation is found, a personalized ddPCR-kit will be used for plasma.
All patients will be followed for five years.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Study participants are recruited from multidisciplinary conferences of head and neck cancer at Örebro University hospital - Region Örebro County, Västmanland's hospital - Region Västmanland and Karolinska University hospital - Region Stockholm. Örebro University hospital is a tertiary referral hospital of three regions in central Sweden (Region Värmland, Region Sörmland and Region Dalarna) and therefore patients from these regions will also be included in this study. All patients with OPSCC at any of the study centers will be asked to participate in CIRCOS. All study participants will sign an informed written consent upon inclusion
Key inclusion criteria (2 listed)
- Oropharyngeal cancer
- Cancer of unknown primary in the head and neck
Key exclusion criteria (4 listed)
- Previous treatment of cancer in the oropharynx.
- Previous treatment of unknown primary tumor.
- Remote metastases
- Patients unwilling or unable to comply with the study protocol and follow-up schedule
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The accuracy of ctHPV-DNA as a biomarker for recurrent disease, measured in PPV and NPV
Time frame: 5 year follow-up
ctHPV-DNA will be evaluated by ddPCR. Two consecutive positive values will be defined as a molecular recurrance. The accuracy of the test will be presented with negative predictive value (NPV) and positive predictive value (PPV) at one, two (interim analysis) and at five year follow-up
2 secondary outcomes
The correlation between molecular tumor burden (copies/mL) and radiological tumor burden (diameter and volume) using Kendall rank correlation coefficient.
Time frame: 3 months follow-up
A comparison between molecular (copies/mL) and radiological response to treatment according to RECIST (Response Evaluation Criteria in Solid Tumors) using Kruskal wallis test.
Time frame: 3 months follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2023.
- Derived from this study: PubMed 40260766Almeren AO, Waenerlund M, Landstrom F, von Beckerath M, Qvick A, Carlsson J, Helenius G. Circulating Tumour DNA as a Complementary Tool for Treatment Evaluation in HPV-Associated Head and Neck Squamous Cell Carcinoma: An Observational Cohort Study. Clin Otolaryngol. 2025 Sep;50(5):831-839. doi: 10.1111/coa.14317. Epub 2025 Apr 22.
- Derived from this study: PubMed 39325260Qvick A, Andersson E, Oldaeus Almeren A, Waenerlund M, Stenmark B, Karlsson C, Karlsson MG, Helenius G. Sensitive and Specific Droplet Digital PCR Assays for Circulating Tumor HPV DNA: Development, Validation, and Clinical Application in HPV-Associated Cancers. Mol Diagn Ther. 2024 Nov;28(6):835-845. doi: 10.1007/s40291-024-00743-9. Epub 2024 Sep 26.
Related trials for Oropharynx Squamous Cell Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 2
A Single Arm Phase II Trial in p16-positive Oropharynx Cancer of Selective Dose De-escalation of nodAl VolumEs at Minimal Risk and Primary Site Disease (SAVED)
Head and Neck Cancer, Head and Neck Squamous Cell Cancer
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
RecruitingObservational study
Head and Neck Carcinoma Clinical Research Platform for Molecular and Blood-based Biomarkers, Treatment and Outcome
Squamous Cell Carcinoma of the Oral Cavity, Squamous Cell Carcinoma of the Oropharynx
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gisela Helenius study director
Örebro University, Sweden
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Oropharynx Squamous Cell Carcinoma and Oropharynx Cancer, run by Region Örebro County at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The accuracy of ctHPV-DNA as a biomarker for recurrent disease, measured in PPV and NPV (time frame: 5 year follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05904327, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2023.