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

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.

Study Overview

• Status: Completed
• Conditions: HPV Positive Oropharyngeal Squamous Cell Carcinoma

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.

• Study Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Department of Otolaryngology - Head and Neck Surgery, Massachusetts Eye and Ear Infirmary

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

AJCC 8 Stage I-III HPV+ Head and Neck Cancer patient undergoing curative intent surgical resection

Description

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

Exclusion Criteria:

• Not meeting all inclusion criteria
• Pregnant
• Receiving treatment for concurrent second malignancy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	Disease free survival in patients with versus without minimal residual disease detection after surgery	2 years
Overall survival	Overall survival in patients with versus without minimal residual disease detection after surgery	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	Disease free survival in patients with versus without minimal residual disease detection after treatment completion	2 years
Overall survival	Overall survival in patients with versus without minimal residual disease detection after treatment completion	2 years

Collaborators and Investigators

• Sponsor: Massachusetts Eye and Ear Infirmary
• Collaborators: Massachusetts General Hospital; National Institutes of Health (NIH); National Institute of Dental and Craniofacial Research (NIDCR)

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: December 9, 2024
• First Posted (Actual): December 12, 2024

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: minimal residual disease; head and neck squamous cell carcinoma; HPV; NGS; liquid biopsy; squamous cell carcinoma; circulating tumor DNA; MRD; HPV+ HNSCC; HPV-DeepSeek
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Carcinoma; Neoplasms, Squamous Cell; Pathological Conditions, Signs and Symptoms; Squamous Cell Carcinoma of Head and Neck; Neoplasm, Residual; Carcinoma, Squamous Cell
• Other Study ID Numbers: 18-653; R03DE030550 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No