Some aspects of this disclosure provide methods and compositions for the treatment of cancer, for example, head and neck cancer, in a subject using ALK1 inhibitors, e.g., ALK1-ECD polypeptides, ALK1-Fc fusion proteins, or ALK1-inhibitory antibodies. In some embodiments, methods and compositions are provided for treating certain cancers with ALK1 inhibitors in combination with a chemotherapeutic platinum agent. In some embodiments, methods are provided for identifying whether a cancer in a subject will react to treatment with an ALK1 antagonist, either alone or in combination with a chemotherapeutic platinum agent, for example, based on a determination that the cancer or the subject is positive for human papilloma virus.