Prospective Observational Study to Validate Circulating HPVDNA and Prognostic Genomic Biomarkers in HPV-associated OPSCC

Study Overview
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Brief Summary
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The primary goal of this study is to examine whether recurrence of HPV-associated OPSCC can be predicted by two factors: 1) mutations in genes called TRAF3 and CYLD, and 2) measurements of circulating HPV DNA in blood plasma. The study will also investigate whether HPV integration is associated with TRAF3 and CYLD mutations, and whether recurrence prediction improves when looking at HPV integration along with TRAF3 and CYLD mutations.

Official Title
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LCCC 2044: Prospective Observational Study to Validate Circulating HPVDNA and Prognostic Genomic Biomarkers in HPV-associated OPSCC

Conditions
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Oropharyngeal Squamous Cell Carcinoma, Carcinoma, Squamous Cell, Head and Neck Squamous Cell Carcinoma, Oropharynx Squamous Cell Carcinoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age T0-T2 N2a-N3 M0 or T3-T4 N0-N3 M0 (AJCC 7th edition) Biopsy proven squamous cell carcinoma of the oropharynx or unknown primary No prior therapy No evidence of distant metastatic disease p16 positive = diffuse ≥ 70% tumor cell expression, with at least moderate (2/3+) staining intensity Planned for receipt of definitive cancer treatment ECOG Performance Status 0-1 Patients must be deemed able to comply with the treatment plan and follow-up schedule. Patients must provide study specific informed consent prior to study entry Exclusion Criteria: All subjects meeting any of the exclusion criteria at baseline will be excluded from study participation: Prior history of radiation therapy to the head and neck Prior history of head and neck cancer. Inadequate pre-treatment tissue sample for tumor genomic analyses

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HPV+ OPSCC Patients<br>Patients with p16+ squamous cell carcinoma of the oropharynx (or unknown primary) who will receive definitive cancer treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of OPSCC | Patients will undergo post-treatment CT scans per institutional standard of care to detect cancer recurrence. Status of recurrence of OPSCC will be confirmed based on biopsy. | From date of therapy completion until biopsy-proven recurrence, assessed up to 5 years | 
| Progression-free survival | Time-to-recurrence will be defined as time lapsed from end (or start) of treatment to first date recurrence (biopsy proven occur later) is detected by CT scans, or death. Otherwise, time-to-recurrence is censored at end of study date. | From beginning or end of treatment until date of CT-detected recurrence or date of death, assessed up to 5 years | 
| Positive Predictive Value | Positive Predictive Value (PPV) is defined as probability that patients with two consecutive positive cHPVDNA (i.e., detectable cHPVDNA) really develop OPSCC recurrence during the study period. | Baseline to up to 5 years | 
| Negative Predictive Value | Negative Predictive Value (NPV) is defined as probability that patients without two consecutive positive cHPVDNA do not develop OPSCC recurrence during the study period. | Baseline to up to 5 years | 
| Quality of Life questionnaire | At specified timepoints before, during, and after treatment, patients will complete a questionnaire comprised of questions from the European Organization for Research and Treatment of Cancer (EORTC) QLQ H&N35, which is for head and neck cancer patients, and EORTC QLQ C30, which is a general cancer assessment. | Baseline until recurrence or up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Papillomavirus, HPV, p16, Oropharynx, OPSCC