• Written informed consent given according to ICH/GCP and national/local regulations must be obtained prior to any screening procedures.

• World Health Organization (WHO) performance status 0-1.

• Age ≥ 18 years.

• Patients with a pathologically proven invasive HNSCC, including oral cavity, oropharynx (independently of HPV status), larynx or hypopharynx.

• Decision by Multidisciplinary Tumor Board of primary treatment with radical radiotherapy with or without concurrent chemotherapy (according to the local guidelines).

• Baseline imaging of the neck:

‣ ≤ 2.5 mm slices CT with iodine injection (independently or during the FDG-PET/CT examination IF acquired in normal diagnostic conditions, i.e. arms along the thorax with diagnostic quality);

⁃ MRI not mandatory but allowed, performed according to centres guidelines;

⁃ FDG-PET/CT.

• Tumor characteristics:

‣ cT-classification (8th TNM staging): T1(except T1 of glottis)-T4a (or, for p16+ oropharyngeal tumors classified cT4, if criteria are compatible with cT4a-stage of p16- tumors).

⁃ cN-classification (8th TNM staging), as assessed by iodine contrasted CT (or MRI) and FDG-PET:

• i. mandatorily cN0 contralaterally to the primary tumor (or on one side of the neck for midline primary tumors):

‣ 1\. smallest diameter \< 5 mm in retropharyngeal level (VIIa);

⁃ 2\. smallest diameter of Küttner node (level IIa) \< 12 mm;

⁃ 3\. smallest diameter \< 10 mm or sum of smallest and largest diameters \< 17 mm in any other level;

⁃ 4\. no central necrosis ;

⁃ 5\. maximal standardized uptake value (SUVmax) ≤ 2.2;

⁃ 6\. in dubious cases (typically 2.2 \< SUVmax \< 4.5 and inconclusive CT or MRI), US-guided FNAC may be required to exclude positive node contralaterally.

∙ ii. ipsilaterally positive (if any of the above mentioned criteria is met), i.e. cN1, cN2a, cN2b, ipsilateral cN3b; or cN1 for oropharyngeal p16+ tumors.

⁃ No distant metastasis.