HIV-Related Malignancies Increasing, Physicians Tell Panel

BETHESDA, Md--The three-member President's Cancer Panel heardevidence from a number of speakers that HIV-related malignanciesare increasing at a significant rate.

Judith Karp, MD, NCI assistant director for applied science, speakingfor Edward Sondik, acting director of NCI, told the panel thatthe putative Kaposi's sarcoma virus, a newly discovered herpesvirus,may be an "agent provocateur" in both Kaposi's sarcomaand HIV-related lymphoma.

She said that scientists face major challenges in initiating clinicalinvestigations of HIV-related malignancies: "There are alimited number of patients, it is sometimes difficult to recruitpatients into investigative clinical trials, and we face challengesin clinical agent development. We need to define meaningful endpointsfor novel agents such as angiogenesis inhibitors and cytokines."

Ellen Feigal, MD, senior investigator in the NCI Cancer TherapyEvaluation Program (CTEP), said that despite logistical, financial,and other problems, it is important to study HIV-related cancers.

She noted that use of antiretroviral therapy and treatments foropportunistic infection have improved survival of HIV-infectedpatients, and thus cancer incidence will continue to rise.

She cited a need to study the relationship between a well-definedonset of impaired immunity and cancer pathogenesis, as well asthe relationship between a virus and cancer development. In addition,she said, recent advances in knowledge about the pathogenesisof HIV related cancers provide an opportunity to test new therapeuticapproaches.

Dr. Feigal urged collaboration among NIH, the pharmaceutical industry,FDA, and independent investigators to develop effective treatmentsand interventions as quickly as possible. She encouraged studiesof therapeutic approaches that take into account the treatmentof the underlying HIV disease as well as the cancer.

Edward L. Trimble, MD, head of the surgery section, CTEP, andJoel Palefsky, MD, Department of Laboratory Medicine, Universityof California, San Francisco, discussed the increasing incidenceof anal intraepithelial neoplasia (AIN) among HIV-infected individuals.

Said Dr. Palefsky, "High-grade AIN is very common in HIVinfection and should be considered a precursor to anal cancer."He also noted that AIN may possibly be implicated in the potentiationof HIV transmission, especially among those who are the recipientsof anal sexual intercourse.

Dr. Palefsky told the panel that the incidence of anal cancerin men who have practiced anal intercourse is about the same asthe incidence of cervical cancer in women prior to the availabilityof Pap smear screening.

Would it not then be reasonable to think, Dr. Palefsky suggested,that aggressive treatment for AIN might prevent anal cancer, orat least significantly decrease its incidence?

Dr. Trimble also talked about the relationship of HIV infectionto cervical cancer. HIV infection can be transmitted sexually,and immunosuppressed women are at particularly high risk of neoplasiaof the lower genital tract.

He pointed out that HIV-positive women with preinvasive diseasehave higher grade lesions, with more frequent multisite involvement,and experience faster progression of lower genital tract neoplasiathan do HIV-negative women.

Philip Pizzo, chief, NCI Pediatric Oncology Branch, said thatthe overall risk for children with immunodeficiency disordersto develop cancer is 4%--330 times greater than the rate of cancerexpected in otherwise healthy children. Moreover, survivors ofchildhood cancer have a 10 to 20 times higher risk of other cancers;being HIV positive makes them even more vulnerable.

Most Common Pediatric Cancers

The most common cancers in HIV-infected children are Kaposi'ssarcoma, Burkitt's lymphoma, immunoblastic lymphoma, and primaryCNS lymphoma, Dr. Pizzo said.

The incidence of non-Hodgkin's lymphoma is 360 times greater inHIV-infected children than in those who are HIV negative, he said.Extranodal involvement occurs in 85% of HIV-positive children(GI tract, bone marrow, heart, kidneys, liver, bone, and brain),and primary CNS disease accounts for 4% to 40% of all non-Hodgkin'slymphoma.