ctHPVDNA in HPV Positive Squamous Cell Carcinoma of the Oropharynx

Circulating Tumor HPV DNA Driven Adjuvant Treatment Deintensification After Transoral Surgery for HPV-Positive Squamous Cell Carcinoma of the Oropharynx

This study is a prospective phase II trial, designed to assess the efficacy and feasibility of adjuvant treatment deintensification guided by ctHPVDNA levels for patients with HPV+OPSCC who undergo transoral surgery and neck dissection.

Study Overview

• Status: Recruiting
• Conditions: Tonsil Cancer; Throat Cancer; Squamous Cell Carcinoma of Oropharynx; HPV Positive Cancer
• Intervention / Treatment: Radiation: Adjuvant Radiation 30 Gray; Radiation: Adjuvant Radiation 40 Gray; Diagnostic test: NavDx

Detailed Description

Oropharyngeal squamous cell carcinoma (OPSCC), commonly known as throat cancer or tonsil cancer, has seen a dramatic rise in incidence over the last twenty years due to the increased incidence of human papillomavirus-positive (HPV) infection and * malignancy within the oropharynx.

The prevailing treatment philosophy within head and neck oncology is that deintensifying treatment could still provide equivalent oncologic outcomes, while further lowering toxicity profiles and improving functional outcomes to minimize the morbidity incurred by patients.

The next frontier in the treatment of HPV+ OPSCC, then, is the potential use of ctHPVDNA in the treatment personalization. Patients could be stratified into risk categories based on their ctHPVDNA levels, and in turn, receive a tailored treatment intensity accordingly.

The goal of this research study is to see if de-intensifying (stopping or scaling back) treatment still provides the same, or perhaps even better, results when compared to standard treatment when using your ctHPVDNA test results as a guide for your treatment.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Azeezat Yekinni; Phone Number: 317-529-6883; Email: ayekinn@iu.edu

Study Locations

• United States
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Recruiting
      • IU Health Joe and Shelly Schwarz Cancer Center
      • Principal Investigator: Michael Sim, MD
      • Contact: Sarah Dutkevitch, RN; Phone Number: 317-278-5618; Email: sdutkevi@iu.edu
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Melvin and Bren Simon Comprehensive Cancer Center
      • Principal Investigator: Michael Sim, MD
      • Contact: Azeezat Yekinni; Phone Number: 317-529-6883; Email: ayekinn@iu.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Pre-Surgery

• Subjects ≥ 18 years old at the time of informed consent.
• Ability to provide written informed consent and HIPAA authorization.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Primary tumor of the oropharynx (palatine tonsil, tongue base, soft palate, lateral or posterior walls of oropharynx).
• Histopathologically confirmed squamous cell carcinoma.
• Detectable ctHPVDNA from blood samples collected prior to treatment.
• Resectable and accessible tumor with high probability of achieving negative margins.
• Smokers and non-smokers included.
• Tumor stage (AJCC 8th edition): T1 or T2, and select T3 tumors that are mobile and do not invade the larynx.
• Nodal stage (AJCC 8th edition): N0, N1 or N2.
• Mobile neck nodes on physical exam if N positive.
• HPV+ tumor, as determined by p16, in-situ hybridization, real-time polymerase chain reaction, or ctHPVDNA.

Post-Surgery

• Subjects with unknown primaries included if primary is definitively identified and resectable with negative margins or if the palatine and lingual tonsils are thoroughly resected and pathologically proven to be negative for a primary.

Exclusion Criteria:

• Serious medical condition preventing general anesthesia for surgery.
• History of previous head and neck radiation or previous head and neck cancer within 3 years.
• Distant metastatic disease present.
• Subjects with synchronous HPV+ oropharynx primaries
• Prior invasive malignant disease within 3 years, with the exception of non-melanoma skin cancer and thyroid cancer, unless patient is deemed cured or disease free, in which case patient may be included in the study.

• Lactating or pregnant women. Women of childbearing potential must have a negative pregnancy test on the day of surgery. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria:

  1. Has undergone a hysterectomy or bilateral oophorectomy; or
  2. Has been naturally amenorrheic for at least 12 consecutive months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adjuvant Radiation 30 Gray; Subjects with undetectable postoperative ctHPVDNA levels after surgery, negative margins, and five or more positive nodes; or confirmed extranodal extension (ENE) (greater than 2 mm) will undergo deintensified radiation treatment of 30 gray.	Radiation: Adjuvant Radiation 30 Gray; If undetectable postoperative ctHPVDNA levels and five or more positive nodes, or confirmed extranodal extension (ENE) (greater than 2 mm) deintensified radiation treatment of 30 gray.; Diagnostic test: NavDx; NavDx is a clinically validated blood test to detect circulating tumor HPV DNA (ctHPVDNA). In this study, ctHPVDNA results, in conjuction with specimen analysis, will be used to assign post-surgical adjuvant treatment.
Experimental: Adjuvant Radiation 40 Gray; Subjects with positive postoperative ctHPVDNA will undergo reimaging to evaluate for potentially operable disease, followed by appropriate surgery as indicated. If surgery is performed, repeat ctHPVDNA levels will be checked, and if then negative, subject will be placed in observation or 30 Gy of radiation depending on nodal status. If repeat ctHPVDNA level is positive, or subject has no obvious operable disease then subject will undergo 40 Gy of radiation.	Radiation: Adjuvant Radiation 40 Gray; If detectable postoperative ctHPVDNA, then reimage to evaluate for potentially operable disease, followed by appropriate surgery as indicated. If surgery is performed, repeat ctHPVDNA levels will be checked, and if then negative, subject will be placed in observation if N0 or N1 disease, and 30 Gy of radiation if N2 disease on final pathologic staging. If repeat ctHPVDNA level is positive, or shows no obvious operable disease, then subject will undergo 40 Gy of radiation.; Diagnostic test: NavDx; NavDx is a clinically validated blood test to detect circulating tumor HPV DNA (ctHPVDNA). In this study, ctHPVDNA results, in conjuction with specimen analysis, will be used to assign post-surgical adjuvant treatment.
Experimental: Observation; Subjects with undetectable postoperative ctHPVDNA levels and either 4 or fewer nodes will have no further adjuvant treatment.	Diagnostic test: NavDx; NavDx is a clinically validated blood test to detect circulating tumor HPV DNA (ctHPVDNA). In this study, ctHPVDNA results, in conjuction with specimen analysis, will be used to assign post-surgical adjuvant treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival	Time from surgery to first disease recurrence or death from any cause	Up to 24 months post initial surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local-reginal Control	Number of subjects with no recurrence at primary oropharyngeal site or in the neck nodal basins	Up to 24 months post initial surgery
Overall Survival	Time from surgery to death from any cause	Up to 24 months post initial surgery
Distant metastasis rates	Assessed by tissue diagnosis or radiographically of recurrent disease at sites away from the primary tumor and neck nodal basins	Up to 24 months post initial surgery
Adverse Events	Number of subjects that experience adverse events, grades 1-5, as assessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) version 5.0	up to 6 months post initial surgery
Swallowing-related Quality Of Life	Assessed using MD Anderson Dysphagia Inventory (MDADI)	3 months, 6 months, 12 months, and 24 months post initial surgery
Gastrostomy tube dependence rates	Assessed by confirmation of feeding tube in-situ in subject and being utilized for nutrition	12 and 24 months post intial surgery

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Michael Sim, MD, Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 1, 2025
• First Submitted That Met QC Criteria: April 1, 2025
• First Posted (Actual): April 7, 2025

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: HPV; transoral surgery; NavDX; HPVctDNA
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Oropharyngeal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Tonsillar Neoplasms
• Other Study ID Numbers: CTO-IUSCCC-0895

Drug and device information, study documents

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