A Phase I/II Study Afatinib/Carboplatin/Paclitaxel Induction Chemotherapy In HPV-Negative HNSCC.

Inclusion Criteria:

1. Patients must have a histologically confirmed diagnosis of squamous cell carcinoma, operable or inoperable tumors, stage III (T3N0-1) and IVA-B (T1-4 N2-3M0 or T4N0-1M0) of oral cavity, oropharynx, hypopharynx and larynx. For patients with oropharynx primary, either HPV negative or HPV positive with a \> 10 pack year tobacco history or current smokers are eligible. HPV status should be determined before the enrollment in only non-smokers with oropharynx primary by HPV in-situ hybridization and/or p16 immunostain.
2. Patients must have measurable disease of primary, nodes or both by clinical and radiographic methods per RECIST v1.1..
3. No prior therapy, including surgery with curative intent, chemotherapy, radiation therapy, immunotherapy, EGFR targeted therapies, or any other investigational agents.
4. Age \>= 18 years.
5. ECOG performance status 0-1.
6. Patients must have normal hepatic, renal and bone marrow function.

   * Absolute neutrophil count \>=1,000/ mm3 Count
   * Platelets \>= 100,000/mm3 Count
   * Total serum bilirubin =\< 1.5mg/dL Level:
   * AST and ALT =\< 2.5 X ULN
   * Alkaline Phosphatase =\< 2.5 X ULN
   * Total calculated creatinine clearance \>= 60 mL/min
7. Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix and/or non-melanomatous skin cancer.
8. Patients with the following within the last 6 months prior to pre-registration must be evaluated by a cardiologist and/or neurologist prior to entry into the study.

   * Congestive heart failure \> NYHA Class II
   * CVA/TIA
   * Unstable angina
   * Myocardial infarction (with or without ST elevation)
9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Any prior radiation above the clavicles.
2. Any prior invasive malignancy (unless non-melanomatous resectable skin or the DFS is 2 years or more).
3. History of allergic reactions attributed to compounds of similar chemical or biological composition to afatinib, or other agents used in study.
4. Cardiac left ventricular dysfunction with resting ejection fraction of less than institutional lower limit of normal ( if no lower limit of normal is defined in the institution, the lower limit is 50%)
5. Gastrointestinal tract disease resulting in an inability to take or absorb oral or enteral medication.
6. Baseline significant gastrointestinal symptoms with diarrhoea as a major symptom or a CTCAE Grade \>1 diarrhoea of any etiology.
7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
8. Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception.
9. Known pre-existing interstitial lung disease (ILD)
10. Pregnant women are excluded.