This is prospective research study which will include patients with recurrent or metastatic squamous cell carcinoma of the head and neck, esophagus and anal canal starting on first-line platinum based chemotherapy or any line of immunotherapy treatment.This study aims to characterize the dynamic changes in genomic, epigenetic, immune profiling and imaging data during treatment with systemic therapy. Patients will have archived tumor samples requested as well as blood samples collected at up to four time points to analyze these changes. Imaging data will be derived from patients' routine CT scans before and after treatment.

Inclusion Criteria:

1. Patients with a histological or cytological diagnosis of Squamous Cell Cancer of the head and neck, esophagus or anal canal who have radiologically confirmed recurrent or metastatic disease.
2. Patients must be of adequate fitness, ECOG 0-1 for systemic therapy, with either standard chemotherapy, immunotherapy or within the context of a clinical trial.
3. Patients must be commencing on a new treatment at time of consent, this can be first line platinum based chemotherapy, or immunotherapy, any line.
4. Patients must be ≥ 18 years old.
5. Patients must have provided voluntary written informed consent.

Exclusion Criteria:

None

Patients with a diagnosis of squamous cell cancer of the head & neck, esophagus, or anal canal who have radiologically confirmed recurrent or metastatic disease.