ctDNA Liquid Biopsy for Early Assessment of Residual Disease in HPV-associated Head and Neck Cancer (Clear-HPVca)

NCT ID: NCT06730412

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 103 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-08-01
• Study Completion Date: 2024-10-31

Brief Summary

The purpose of this study is to test a new liquid biopsy assay for detecting residual disease after surgery in patients with HPV-associated head and neck cancer.

Detailed Description

Human papillomavirus associated head and neck squamous cell carcinoma (HPV+HNC) is the most common HPV-associated cancer in the United States. Surgery is a common approach for primary treatment of early-stage HPV+HNC. Many patients who undergo surgery receive adjuvant radiation or chemoradiation therapy to treat potential residual disease, which is currently predicted based on clinicopathologic risk factors including positive margins, extranodal extension, multiple positive lymph nodes, vascular invasion, and lymphatic invasion. However, there are limitations in predicting residual disease based on the use of these features alone - the use of clinicopathologic risk factors for prediction is non-standardized and has poor individualized predictive and prognostic capacity. Currently, there are no established biomarkers to predict residual disease.

Circulating tumor DNA (ctDNA) is an emerging minimally invasive prognostic biomarker, for detecting molecular residual disease (MRD) and predicting recurrence in multiple solid cancers. Prospective trials in cancers such as colorectal cancer have demonstrated not only strong Disease Free Survival (DFS) prognostic capacity but also Overall Survival (OS). Previous studies have demonstrated that HPV+HNCs release circulating tumor HPV DNA (ctHPVDNA) into the blood where it serves as an accurate real-time biomarker of disease status after surgery. In patients without pathological risk factors, ctHPVDNA is rapidly cleared after surgery. In patients with residual disease, ctHPVDNA remains elevated after surgery. However, initial studies have showed that patients with microscopic levels of residual disease are often not detected by current approaches using droplet digital PCR (ddPCR), suggesting significantly more sensitive assays are necessary.

HPV-DeepSeek is an HPV whole genome next-generation sequencing assay which is significantly more sensitive than ddPCR-based approaches. The investigators aim to conduct a prospective observational cohort study of HPV+HNC patients treated with curative intent surgery to test the primary hypothesis that patients with MRD detection after surgery will have inferior 2-year DFS and OS and the secondary hypothesis that patients with MRD detection after treatment completion (surveillance) will have inferior 2-year DFS and OS.

Conditions

HPV Positive Oropharyngeal Squamous Cell Carcinoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

HPV-associated head and neck cancer patients treated with surgery

AJCC 8 Stage I-III HPV+ head and neck cancer patients treated with curative intent surgery

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Greater than or equal to 18 years of age
• Newly diagnosed, untreated, histologically confirmed HPV-associated head and neck cancer
• Scheduled for curative intent resection as primary treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Pregnant
• Receiving treatment for concurrent second malignancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Dental and Craniofacial Research (NIDCR)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Massachusetts Eye and Ear Infirmary

OTHER

Sponsor Role: lead

Responsible Party

Daniel L. Faden, MD

Assistant Professor, Harvard Medical School

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Otolaryngology - Head and Neck Surgery, Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

R03DE030550

Identifier Type: NIH

Identifier Source: secondary_id

View Link

18-653

Identifier Type: -

Identifier Source: org_study_id