The present invention relates to methods for identifying, assessing, preventing, and treating cancer (e.g., head, neck, and/or lung cancers in humans). A variety of PD-LI isoforni biomarkers are pro v ided, wherein alterations in the copy number of one or more of the biomarkers and/or alterations in the amount, structure, and/or acti vity of one or more of the biomarkers is associated with cancer status and indicates amenability to treatment or prevention by modulating PD-1 and/or PD-L! levels.