AIDS-Associated Malignancies
On this page:
Prevalence
AIDS and HIV infection continue to be major public health concerns. From 1981 to 2001, 816,149 cases of AIDS were reported to the CDC, 18 percent of which were in women. Heterosexual transmission of HIV increased from 3 percent in 1985 to 28 percent in 2001. 65 percent of HIV-positive women are infected by this route. Approximately 506,154 persons are currently living with HIV infection or AIDS in the United States. Of those, 141,048 adults and adolescent women are living with AIDS, and 49,226 are living with HIV infection. In 2001, 41,744 new cases of AIDS were reported to the CDC; one third were in women. There were also 35,051 new cases of HIV infection reported; however, this is likely an underestimate since not all states report new cases.
While the numbers of deaths per year in the United States due to AIDS has decreased in the era of highly active antiretroviral therapy (HAART), the numbers of persons living with the disease has increased. The longer life expectancy of HIV+ people with access to HAART may increase their cumulative risk of developing cancer to rates similar to solid organ transplant recipients whose lifetime risk of cancer is increased due to iatrogenic immune suppression.
AIDS-Associated Malignancies. The long-term risks of developing cancer for HIV+/AIDS patients are not yet known. Malignancies occur in more than 30 to 40 percent of HIV+ patients during the course of their disease and include: non Hodgkin's lymphoma, cervical cancer, anal cancer, and Kaposi's sarcoma (KS). Although KS is extremely rare among women, non Hodgkin's lymphoma (NHL) currently ranks sixth in overall female cancer incidence and mortality. In addition, there is an increased incidence of NHL in women from the pre-HAART to HAART period. The risk of cervical neoplasia is five times higher in women with HIV infection than in uninfected women, due to the extraordinarily high prevalence of oncogenic HPV infection among HIV seropositive women. Cervical HPV rates in HIV-infected women are 43 percent versus 24 percent in uninfected women. Rates for anal HPV in HIV-infected women are 79 percent, compared to uninfected women, whose rates are 53 percent.
Women's Interagency HIV Study (WIHS). Since 1995, NCI has provided supplemental funds to support malignancy studies in the NIAID/NICHD/NIDA/NIDCR-funded WIHS, the largest U.S. study of HIV infection in women. HIV-infected women have increased incidence rates for Kaposi sarcoma (>200-fold), non-Hodgkin's lymphoma (23-fold), and lung cancer (10-fold) when compared to SEER rates. No significant increases have been detected among HIV-infected and high-risk uninfected WIHS women for lung cancer after adjusting for cigarette smoking. Only one confirmed case of invasive cervical cancer has occurred to date in an HIV-infected woman. Despite concerns to the contrary, no increased risk of breast cancer or unusual types of breast tumors have been detected in over 5,000 woman-years of follow-up. HIV-infected women who initiated highly active antiretroviral therapy against HIV experienced significant reductions in overall cancer risks. WIHS women have high rates of infection with oncogenic tumor viruses, including hepatitis C and human herpes virus 8.
Treatment
Aids Malignancy Program (AMP). NCI developed a multi-component AMP to assist the research community in studying the interplay of viruses, immune dysfunction, aberrant growth factor expression, and the development of cancer in AIDS patients, with the goal of developing more effective treatment regimens. The main components of the program are the AIDS Associated Malignancies Clinical (AMC) Trials Consortium and the AIDS and Cancer Specimen Resource (ACSR). The ACSR contains or provides access to over 100,000 specimens collected from cohort studies, clinical trials, and other research.
The AMC unites 15 main member sites that conduct innovative treatment trials for AIDS associated malignancies, providing access to tissue specimens and clinical data from patients. Important clinical information from completed AMC trials includes: Oral 9-cis-retinoic acid was shown to be an active anti-tumor drug for AIDS-related KS with an overall response rate of 37 percent; CHOP or a modified dosage of CHOP chemotherapy is an effective and tolerable treatment for NHL in HIV+ patients on HAART; IFN-a2ß administered to HIV+ KS patients on protease inhibitors was well tolerated with overall response of 39 percent; in a phase I trial, Oral COL-3 administered once daily to HIV+KS patients is well tolerated, with overall response of 44 percent; and a phase III study indicated that IM862 is ineffective against AIDS-KS, in contrast to earlier phase I and II trials.
EPOCH. An NCI study of dose-adjusted EPOCH (etopside, prednisone, vincristine, cyclophosphamide, doxorubicin) chemotherapy with HAART suspension for untreated AIDS-Related Non-Hodgkin's lymphoma (ARL) patients showed disease-free and overall survival of 92 and 60 percent, respectively, at 53 months median followup. Results seemed to correlate with high MIB-1 and possible upward CD4 risk migrations and providing emphasis for the importance of tumor biology in treatment outcomes. The results also suggest that by forestalling immune depletion, HAART has shifted tumor pathogenesis and confers no specific benefit during chemotherapy treatment.
A European-U.S.study showed a reduction in HIV transmission in pregnant women treated with antiretroviral therapy, caesarian section, with greater birth weight babies, and higher CD4 cell count.
