BETHESDA, Md--A review of 10 years' experience with HIV-infected patients treated at University Hospital, Newark, NJ, revealed significantly elevated levels of several types of cancers, but a surprising dearth of invasive cervical cancers, which prompted the study's lead author to suggest dropping cervical cancer from the list of AIDS-associated malignancies.
Stanley H. Weiss, MD, and colleagues at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School and University Hospital, examined data from the hospital's cancer registry of patients treated from 1986 through 1995.
They compared the proportion of specific cancers diagnosed among 118 HIV-positive cancer patients (93 male, 25 female) with those occurring in 3,289 individuals not known to carry HIV, and also compared their outcomes.
"Newark is clearly an HIV epicenter," Dr. Weiss told the first National AIDS Malignancy Conference held at the National Cancer Institute. "There are particularly high rates among women and injection drug users, providing an interesting community in which to look at issues related to cancer."
Excess Kaposi's Sarcoma and NHL
The tumor types among the HIV-positive patients included 45 Kaposi's sarcoma (38%); 22 lymphoreticular (19%), which included 16 non-Hodgkin's lymphoma (NHL), 3 Hodgkin's, and 3 leukemia; 16 lung (14%); 13 head and neck (11%); 11 gastrointestinal (9%); 3 breast (2.5%); 3 invasive cervical; and 5 miscellaneous (4%).
Not surprisingly, HIV patients showed significant excesses of Kaposi's sarcoma and non-Hodgkin's lymphomas, with odds ratios of 66 and 8, respectively. Other cancers with statistically excessive ratios were lung (2.7), leukemia (3.4), and Hodgkin's lymphoma (4.4).
Dr. Weiss and his colleagues had previously reported an association between HIV infection and cervical dysplasia, with the highest rates among those with the fewest CD4 cells. They had also documented that, in their region, historically the majority of HIV-infected women infrequently or never had cervical cytology screening, despite physician counseling.
Said Dr. Weiss: "We therefore anticipated finding an excess of invasive cervical cancer." He noted that the total of 230 cervical cancers in his series constituted 14% of the 1,654 cancer registry cases among women. "This proportion is significantly elevated compared to national data [8% in 1993 for uterine cancers, including invasive cervical cancers]," he said. "Cervical cancer remains epidemic in our region."
To the investigators' surprise, cervical cancer among HIV-infected women was not increased in the registry study. The reduced odds ratio was 0.87 (not statistically significant), Dr. Weiss said.
A University Hospital clinic run by Dr. Patricia Kloser has cared for several thousand HIV-positive women, he said. All of the cervical cancers occurring among women at this clinic were already in the cancer registry records. The last HIV clinic case of cervical cancer during the study period occurred in 1992, "so despite much other cervical pathology, it has not been translating into invasive cancer here," Dr. Weiss pointed out.
Cervical cancer was added in 1993 as an AIDS-defining condition among HIV-positive women, "despite there then being only 18 such cases described in the world," he said.
The strength of the association with cervical dysplasia was persuasive on a biologic basis, but, he said, "our new data suggest that we should reconsider this decision."
More important, Dr. Weiss noted, the findings suggest that a biologic progression from dysplasia to invasive cancer may involve a step in the carcinogenesis pathway that is somehow impeded or reduced among HIV-positive individuals.
"If so, our data offer a clue that alternative therapies, perhaps immunologic, may exist that could reduce the risk of cervical cancer in all women," Dr. Weiss commented.
With the exception of Kaposi's sarcoma, the overall outcome among all the HIV-infected patients in this study was "no worse than expected for patients with cancer of the same site and stage without known HIV infection," Dr. Weiss said. However, whites in both groups had a longer median survival time than nonwhites.
The study patients were 69% black, 17% Hispanic, and 14% white. Of the 118 HIV patients, 47% smoked cigarettes, 12% never smoked, and the smoking status of the others was unknown.
Mixed Reaction to Proposal
Dr. Weiss' proposal to drop invasive cervical cancer as AIDS defining met mixed reactions at the conference.
"I would advocate that we do not change the definition," said Mitchell Maiman, MD, of the State University of New York Downstate Medical School in Brooklyn. "Cervical cancer is by far our leading gynecological malignancy, unlike the rest of the country."
Dr. Maiman described experience at his institution that contrasted strikingly with that presented in the New Jersey study. He noted that while women account for 15% of US AIDS cases and 19% of AIDS cases in New York City, they make up 26% of AIDS diagnoses in Brooklyn.
"Thus far, we're running an HIV positivity rate of 18% or 19% in women who come in with invasive cervical cancer under the age of 50," he said. "Those are pretty high rates and certainly indicate that HIV testing in all patients with cervical cancer in high-risk populations is a good idea."
Dr. Maiman reported data drawn from an initial pool of 221 women younger than age 51 with cervical cancer. Of these, 149 were tested for HIV and 28 were positive. HIV-infected women tended to have a more advanced stage of cervical cancer when diagnosed.
"The majority of these patients came in with advanced disease, that is, stage ID2," Dr. Maiman said. In contrast, 43% of HIV-negative patients had early-stage disease (stage IA or IB1). "Most important," he said, "most of the HIV-positive patients came in asymptomatic with regard to HIV infection. So if you don't test, you don't know."
The Downstate data indicate that HIV-positive women who develop cervical cancer are not among the more immunosuppressed AIDS patients and that their outcome is worse.
"Sixty-four percent had CD4 counts between 200 and 500, and another 16% had counts over 500," Dr. Maiman noted. "About half the patients who are HIV negative recurred over time, while almost 90% of the patients who are HIV positive recurred."
Downstate's experience since the study is slightly better, he added. "We now have a few patients who have more prolonged courses."
Dr. Maiman also noted a high prevalence of oncogenic strains of human papillomavirus in women with AIDS. "We must look at HPV as almost a ubiquitous or opportunistic infection in HIV-positive patients," he said.
Dr. Weiss strongly concurred that HPV is a serious problem in urban communities and is highly prevalent among HIV-infected women. Resources for gynecologic care remain critically important for these regions, he said.
Dr. Weiss added that "a research application to explore and explain the differences in these local findings of cervical cancer incidence is under current development as a joint endeavor between researchers at Downstate and our group."