Inclusion of new biomarkers to improve the personalized treatment approach for HPV-positive and -negative oropharyngeal squamous cell carcinoma (OPSCC) patients is urgently needed. Emerging evidences suggest that mutations in epigenetic regulators, as well as epigenetic changes, deeply influence the biology of OPSCC, thus representing attractive targets for the definition of novel molecular markers for this malignancy. Based on these considerations, our project aims to retrospectively identify a new mutational and epigenetic signature to identify OPSCC patients at high risk of early relapse, and to set up a new multicenter prospective study in order to validate it

Inclusion Criteria:

• newly diagnosed, previously untreated, histologically confirmed stage III-IVa OPSCC, according to AJCC 7th Edition,
• managed with definitive treatment modality (either radical surgery plus adjuvant radiotherapy ± chemotherapy or definitive chemo-radiotherapy)
• minimum follow up of 2 years or who had disease recurrence within 2 years after the end of treatment.
• neoplastic lesion contains ≥ 70% neoplastic cells

Exclusion Criteria:

Patients:

• with distant metastases at diagnosis,
• who have been managed with palliative intent;
• with previous history of head and neck cancer are not eligible

Caucasian patients, with newly diagnosed, previously untreated, histologically confirmed stage III-IVa OPSCC