Sixty percent of newly diagnosed head and neck squamous cell carcinomas (HNSCCs) are at a locally advanced (LA) stage. Depending on tumor site, stage, and resectability, locoregional failure rates can range from 35% to 65%. The persistence of residual disease at the end of treatment is a major prognostic element but is not always reliably assessed by current imaging techniques. Up to 40-50% of patients have residual adenomegaly and only 30% have viable disease when further adenectomy is performed. Sensitive and reproducible detection of residual disease after treatment is a major challenge in this patient category.

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) guided surveillance, with a negative predictive value of 95-97%, has proven to be non-inferior to cervical curage in HNSCCs with residual adenomegaly. Cervical curage is now indicated only if the response assessed by PET-CT is incomplete. Nevertheless, the ability of PET-CT to predict treatment failure is unsatisfactory due to a high frequency of false positives, because of inflammatory changes, with a positive predictive value of about 20-50%.

Circulating tumor DNA (ctDNA) may provide a more reliable assessment of response to potentiated radiotherapy. Liquid biopsy monitoring of response in patients treated with potentiated radiation therapy for locally advanced HNSCCs a has been shown to be feasible. In 85% of patients, ctDNA is detectable and correlates significantly with tumor volume and response to treatment. In addition, one study showed that post-radiotherapy analysis of circulating HPV16 viral DNA (cvDNA) in patients with HPV16-related HNSCCs complemented PET-CT and helped guide management decisions. HPV16 cvDNA and PET-CT have similar negative predictive values, whereas the positive predictive value is higher for HPV16 cvDNA (100% versus 50%). Nevertheless, current data are insufficient to allow routine use of this marker.

This is a multicenter, single arm, open study for patients with a locally advanced head and neck cancer for which a potentiated radiotherapy is indicated.

Inclusion Criteria:

• Age ≥ 18 years and ≤ 80 years
• Histologically confirmed, never treated squamous cell carcinoma with lymph node involvement
• squamous cell carcinoma p16+or p16-, stage III (N1), IVa or IVb (UICC classification 8th edition), N1 minimum, and oropharyngeal sqamous cell carcinomas p16+ stage I or II, N1 minimum, resectable but not operated or unresectable, with indication for concomitant or sequential radiochemotherapy with induction chemotherapy using Docetaxel, Platinum, 5-Fluorouracil (TPF or modified TPF according to the practices of the investigating centers)
• Oral cavity, oropharynx, hypopharynx or larynx, cervical adenopathies without primary
• Availability of FFPE samples prior to treatment initiation
• Detection of circulating DNA in the initial blood sample
• Obtaining informed consent from the patient
• Affiliation to the French social security system

Exclusion Criteria:

• Tumor of the nasopharynx, sinuses, nasal cavity, salivary glands or thyroid cancer
• Treatment by exclusive radiotherapy
• Contraindication to cervical lymph node dissection
• Metastatic disease (stage IVc)
• Previous treatment for head and neck cancer
• History of other cancer in the last 3 years (except carcinoma in situ, basal cell skin carcinoma, localized prostate cancer Gleason 6)
• Pregnant or breastfeeding woman
• Patient under guardianship or curators
• Psychological disorder (cognitive disorders, vigilance disorders, etc.) or social reasons (deprivation of liberty by judicial or administrative decision) or geographical reasons that could compromise the medical follow-up of the trial or compliance with the treatment