Pathogenesis of non-AIDS-defining cancers: a review

As the AIDS epidemic advances, the number of HIV-infected subjects developing AIDS-related neoplasms is rapidly increasing, and the spectrum of malignancies encountered is expanding. Several non-AIDS-defining cancers are being reported at an increasing incidence in HIV-infected individuals, including anal, skin, oral mucosa, head and neck and lung carcinomas, testicular tumors, and pediatric soft-tissue sarcoma. There appears to be an emerging role for various concurrent viral infections in the HIV-infected host that are likely implicated in the pathogenesis of some nondefining-AIDS neoplasms. Our recent findings in HIV-associated lung cancers and in the precursor lesions of cervical carcinoma suggest that wide-spread genomic instability, as manifested by the development of increased numbers of microsatellite alterations (MAs), may occur frequently in HIV-associated tumors and they may play an important role in the pathogenesis of those neoplasms. Although the mechanism underlying the development of increased MAs is unknown, it may play a crucial role in the development of many HIV-associated tumors. It will be important to track the epidemiological and biological features of non-AIDS-defining cancers in HIV-infected patients, and compare them to those tumors in the general population. It is likely that further clues about malignant transformation and oncogenesis unraveled in the HIV setting will have broad clinical implications.