Disclosed are methods for treating hematologic and solid cancers in a subject, the method comprising administering locally or systemically a therapeutically effective amount of a HRVA2.s and/or HRVA45.s alone or in combination with FDA approved or experimental immunomodulatory agents such that some cells of the cancer undergo viral oncolysis, wherein the host immune system is engaged culminating in host immune activation and tumor regression in the human or animal host. Disclosed are methods for treating viral induced lesions of the skin, including HPV driven papillomas in a subject, the method comprising administering a therapeutically effective amount of HRVA2.s and/or HRVA45.s alone or in combination with immunomodulatory agents such that some cells of the papilloma cells undergo selective viral lysis, wherein the host immune system is engaged culminating in host immune activation and papilloma in the subject.