HPV-associated Oropharyngeal Carcinoma (HPV-OPC)

Official title

Validation of a New Method for Monitoring HPV Infection in Patients With Head and Neck Cancers

Overview

This study focuses on the longitudinal monitoring of HPV infection in patients with head and neck cancers, particularly oropharyngeal carcinoma (OPC), using a new electrochemical detection method. This method has already been successfully developed and validated for cervical cancer. The aim of the project is to monitor the dynamics of HPV viral load before the start of treatment and during conservative radiation therapy or concurrent chemoradiation therapy. HPV will be analyzed from oral swabs, oral cavity washings, and plasma as part of a small prospective study. The results of the new method will be correlated with standard techniques, particularly qPCR. Longitudinal monitoring may contribute to the individualization and potential de-escalation of treatment in selected patients.

Detailed description

Patients with HPV-positive head and neck tumors, primarily OPC, who are indicated for conservative radiation therapy or concurrent chemoradiation therapy will be enrolled in the study. At defined time points (before the start of treatment and during treatment), oral swabs, oral cavity washings, and peripheral blood samples will be collected, from which plasma will be isolated for analysis of viral ctDNA. We estimate approximately 20 patients with OPC indicated for radiotherapy alone or concurrent chemoradiotherapy who are p16-positive. Negative controls will be patients with OPC indicated for radiotherapy alone or concurrent chemoradiotherapy who are p16-negative (approximately 10-15).

Interventions

• Diagnostic test HPV p16
  Monitoring changes in HPV DNA levels during therapy can predict the clinical response to treatment and, in the future, may allow for the safe de-escalation of the intensity of radiation therapy or chemoradiation in selected patients. We will also determine the appropriate method for collecting DNA samples so that, in the future, sampling can be as minimally invasive as possible while maintaining the necessary sensitivity and specificity. By comparing the dynamics of local mucosal samples with th
• Diagnostic test HPV testing - positive results
  Monitoring changes in HPV DNA levels during therapy can predict the clinical response to treatment and, in the future, may allow for the safe de-escalation of the intensity of radiation therapy or chemoradiation in selected patients. We will also determine the appropriate method for collecting DNA samples so that, in the future, sampling can be as minimally invasive as possible while maintaining the necessary sensitivity and specificity. By comparing the dynamics of local mucosal samples with th
• Diagnostic test HPV testing - negative results
  Monitoring changes in HPV DNA levels during therapy can predict the clinical response to treatment and, in the future, may allow for the safe de-escalation of the intensity of radiation therapy or chemoradiation in selected patients. We will also determine the appropriate method for collecting DNA samples so that, in the future, sampling can be as minimally invasive as possible while maintaining the necessary sensitivity and specificity. By comparing the dynamics of local mucosal samples with th

Primary outcome measures

• Correlation of HPV DNA Levels Measured by a New Electrochemical Method Versus Standard Quantitative Polymerase Chain Reaction (qPCR) [Time frame: Baseline (pre-treatment), Week 4 of radiotherapy, end of radiotherapy (approx. Week 7), and 3 months post-radiotherapy]

Secondary outcome measures (1)

• Change From Baseline in HPV16 Viral Load in Plasma, Oral Swabs, and Oral Rinses [Time frame: Baseline (pre-treatment), Week 4 of radiotherapy, end of radiotherapy (approx. Week 7), and 3 months post-radiotherapy.]

Eligibility criteria

Inclusion criteria

• a patient with an oropharyngeal tumor indicated for curative radiation therapy or chemoradiotherapy
• if radiation therapy or chemoradiotherapy was preceded by surgery, the patient may be enrolled if the lesion persists on imaging studies
• the lesion must be a histologically confirmed squamous cell carcinoma with known p16 status
• age ≥ 18 years
• the subject must be willing and able to provide written informed consent for specimen collection
• ability to communicate effectively with the investigator in the local language, and ability to understand and comply with the study requirements

Exclusion criteria

• previous induction chemotherapy
• unknown p16 status, incomplete or inadequate histology-e.g., adenocarcinoma, melanoma, lymphoma,
• previous radiation therapy to the oropharynx
• palliative patients indicated for accelerated radiation therapy with a treatment duration of < 5.5 weeks
• age < 18 years
• pregnant or breastfeeding women
• patients in the terminal stage of life
• severe alcohol and/or drug abuse during treatment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Health services research

Study locations

Czechia · 1 center

• Masaryk Memorial Cancer Institute — Brno

Publications

• Rettig EM, Faden DL, Sandhu S, Wong K, Faquin WC, Warinner C, Stephens P, Kumar S, Kuperwasser C, Richmon JD, Uppaluri R, Varvares M, Sethi R, Hanna GJ, Sroussi H. Detection of circulating tumor human papillomavirus DNA before diagnosis of HPV-positive head and neck cancer. Int J Cancer. 2022 Oct 1;151(7):1081-1085. doi: 10.1002/ijc.33996. Epub 2022 Mar 16. PMID 35262203
• Das D, Hirayama S, Aye L, Bryan ME, Naegele S, Zhao B, Efthymiou V, Mendel J, Fisch AS, Guan Z, Kroller L, Michels BE, Waterboer T, Richmon JD, Adalsteinsson V, Lawrence MS, Crowson MG, Iafrate AJ, Faden DL. Circulating tumor human papillomavirus DNA whole genome sequencing enables human papillomavirus-associated oropharynx cancer early detection. J Natl Cancer Inst. 2026 Jan 1;118(1):58-67. doi: PMID 40925715
• Izadi N, Strmiskova J, Anton M, Hausnerova J, Bartosik M. LAMP-based electrochemical platform for monitoring HPV genome integration at the mRNA level associated with higher risk of cervical cancer progression. J Med Virol. 2024 Oct;96(10):e70008. doi: 10.1002/jmv.70008. PMID 39420658
• Izadi N, Sebuyoya R, Moranova L, Hrstka R, Anton M, Bartosik M. Electrochemical bioassay coupled to LAMP reaction for determination of high-risk HPV infection in crude lysates. Anal Chim Acta. 2021 Dec 1;1187:339145. doi: 10.1016/j.aca.2021.339145. Epub 2021 Oct 5. PMID 34753575

Identifiers

NCT: NCT07718620 · A6/26

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗