RB1 and osteosarcoma: The p16 protein is also increased in a variety of non‐HPV‐related neoplasms including esophageal squamous cell20 and ovarian21 carcinomas and osteosarcomas.22 Presumably p16 has lost its tumor suppressive function in such cells via inactivation of Rb or other proteins involved in the Rb pathway, although the exact molecular mechanisms for increased p16 have not been defined in all cases.