Study Background and Rationale Head and neck cancer (HNC) is the sixth leading cause of cancer-related death, with over 650,000 new cases diagnosed worldwide each year. About 60% of patients are diagnosed at an advanced stage, and many experience recurrence or spread despite surgery, radiation, or chemotherapy. Major risk factors include tobacco and alcohol use, prior radiation therapy, and infection with human papillomavirus (HPV). The prognosis differs across patients due to HPV infection and genetic factors. HPV is commonly found in cancers of the tonsils and throat. Patients with HPV-positive tumors generally respond better to treatment and live longer than those who are HPV-negative. Conversely, patients with certain genetic changes, like EGFR amplification, tend to have worse outcomes. HNC can develop in the oral cavity, throat, larynx, nasal cavity, nasopharynx, and salivary glands. Squamous cell carcinoma caused by smoking is the most common type, but other types like salivary gland cancer or adenoid cystic carcinoma also occur, making the disease clinically diverse. Treatments exist, but for advanced cancers, such as advanced laryngeal cancer, the 5-year survival rate is only around 40%. HNC also affects the face and throat, which can cause breathing problems, difficulty swallowing, voice changes, and significant impact on quality of life. The effectiveness of treatment is limited by tumor diversity and complex interactions between cancer cells, immune cells, and surrounding tissue (tumor microenvironment, TME). Most research so far comes from Western populations, but genetic and viral differences in Asian patients require domestic studies. To provide personalized treatment, it is essential to collect clinical and genetic data from Korean patients and study their tumors and TME. Need for Long-term Follow-up Studies Even early-stage HNC can recur locally, with recurrence rates reported between 20-57%. Recurrent or metastatic HNC has poor prognosis, with only 20-30% surviving five years. HNC usually progresses from pre-cancerous lesions to primary tumors and then spreads to lymph nodes. The molecular mechanisms behind this progression are not fully understood. Various factors including smoking, alcohol, and HPV infection influence HNC development. HPV-positive patients show better outcomes, but their immune response may be suppressed. Therefore, continuous observation of HNC patients from early disease to recurrence is necessary to identify biomarkers that predict outcomes and to find more effective treatments. Importance of Studying Tumor Microenvironment Immune checkpoint inhibitors (ICIs) combined with chemotherapy have improved survival in HNC. For example, pembrolizumab plus chemotherapy extended median overall survival to 13 months versus 10.7 months with standard treatment. Patients with higher PD-L1 expression responded better, but some high PD-L1 patients still did not respond, and some low PD-L1 patients responded well. Clear biomarkers to predict who will benefit from ICIs are still lacking. Role of Samsung Medical Center In Korea, about 3,000 new cases of lip, oral, and throat cancer occur annually. Samsung Medical Center treated 550 of these patients in 2021, about one-fifth of national cases. More than half presented with advanced disease. Five-year survival rates for patients at Samsung Medical Center are higher than national averages: 78.5% overall, 93.2% for local tumors, and 37.8% for metastatic disease. These data show the importance of collecting patient information and samples for ongoing research. Study Objectives This study aims to: Collect clinical information from HNC patients at Samsung Medical Center. Collect tissue and blood samples at diagnosis, before and during treatment, and at disease progression or suspected recurrence. Identify biomarkers that can guide personalized treatment in the future. Study Design Eligibility Inclusion Criteria: Adults 20 years or older. Histologically confirmed HNC at any head and neck site (oral cavity, pharynx, larynx, nasal cavity, salivary glands, or other locations). Patients diagnosed elsewhere are eligible if pathology is confirmed at Samsung Medical Center. Various HNC-related cancer types including squamous cell carcinoma, adenocarcinoma, undifferentiated carcinoma, and others. Scheduled for or previously received appropriate treatment (surgery, radiotherapy, chemotherapy, or immunotherapy). Able to understand and sign informed consent. Exclusion Criteria: Not meeting inclusion criteria. Any other reason deemed unsuitable by the investigator. Sample Size: Approximately 350 patients per year will participate, based on the number undergoing biopsy and blood collection at Samsung Medical Center. Duration The study will last 60 months from IRB approval (\ December 31, 2030). Data and Sample Collection Clinical Data: Collect demographics, diagnosis details (location, stage, HPV status), medical history, smoking/alcoh