A Glass Half Full: Cancer Risk for People Living With HIV

Table of Contents

• Introduction
• A Dividing Line: Before and After HAART
• Apples to Apples
• AIDS-Defining Cancers
• The New Frontier: Non-AIDS-Defining Cancers
• Hodgkin's Lymphoma
• Oncogenic Viruses
• The Role of Immune Health
• Prevention
• Next Steps
• Closing Note
• Selected Sources

Introduction

A review of cancers among people with HIV before and since the mid-1990s advent of HAART (highly active antiretroviral therapy) quickly reveals a "before" and "after" experience. Before HAART made it possible to suppress HIV replication to a low or even undetectable level, certain cancers were fairly common in this population.

These "AIDS-defining cancers" (ADCs) are Kaposi's sarcoma (KS, seen mainly in men), non-Hodgkin lymphoma (NHL) and invasive cervical cancer (caused by certain types of human papillomavirus, or HPV). Having one of them while infected with HIV constitutes an AIDS diagnosis. Although anal cancer is caused by the same HPV types and has the same clinical course as cervical cancer, it is not classified as an AIDS-defining cancer.

HAART greatly reduces the risk for both ADCs and the various non-AIDS-defining cancers (NADCs) seen disproportionately in people with HIV. It strengthens the immune system's ability to keep in check such potentially cancer-causing viruses as HPV, hepatitis B virus (HBV) and hepatitis C virus (HCV), as well as the other opportunistic infections that prey on a weakened immune system.

In resource-limited countries, cancer has been blamed for fewer HIV-related deaths. But some experts suggest this is either due to the lack of recognition and recording of malignancies, or because HIV positive people are still dying from AIDS-related causes before they have lived long enough to develop cancers, which often take years to emerge.

In major United States cities such as San Francisco, an HIV/AIDS epicenter since the start of the epidemic, the picture of cancer risk among long-term HIV survivors is very different than in less wealthy regions. Here, most people who know they have HIV are managing the disease with HAART, and doctors predict that many are likely to have a more normal lifespan.

But even in San Francisco, HIV physician Christopher Hall, M.D., observed that managing cancers, particularly KS and squamous cell carcinoma of the anus and rectum, "is becoming a bigger part of what we do." He added, "we've become closer to our oncology colleagues and get them involved in cases."

As we age, our immune systems weaken and make us more susceptible to cancers of various sorts, regardless of HIV status. People with HIV are at greater risk than their HIV negative age peers because their immune systems are already challenged. Chronic inflammation and simply living longer with other potentially harmful viral infections increases the risk of cancer developing over time.

While HAART can strengthen the immune system and weaken the effects of HIV, it cannot make us choose to eat nutritious food, moderate alcohol intake, exercise regularly, reduce our number of sexual partners and use condoms, quit smoking, or get the recommended screenings, vaccines and treatments needed to avoid complications from other infections.

Today, HIV positive people who are on HAART and receiving regular medical care have a number of tools to minimize the risk for cancer -- tools that were unavailable in the epidemic's early years.

A Dividing Line: Before and After HAART

The beginning of the HAART era in 1996 marks a dividing line in the rates and types of cancers affecting people with HIV.

Antiretroviral therapy has greatly reduced HIV positive people's risk for AIDS-defining cancers, according to a review of cancer occurrence in the HAART era by Michael J. Silverberg, Ph.D., a cancer researcher with Kaiser Permanente Northern California, and longtime HIV and cancer expert Donald Abrams, M.D., of the University of California, San Francisco (UCSF).

For example, a U.S. military study of 4,500 people with HIV looked at rates of cancer between 1984 and 2007 -- that is, 12 years before HAART was introduced until 11 years after it became available. Before HAART became the standard of care for HIV disease, 80% of cancers in people with HIV were AIDS-defining. Five years later, 71% of cancers seen in HIV positive people were deemed unrelated to AIDS.

Apples to Apples

Most studies of HIV positive people's cancer risk have examined whether HAART has lowered that risk. But Silverberg said that comparing the experience of people with HIV before (or still not on) HAART to today "is comparing apples and oranges."

Silverberg and his colleagues examined the histories of 20,277 HIV patients at Kaiser Permanente Northern California, who were unusual in that they all had health insurance. This means they were, more or less, on a level playing field as far as their ability to access medical care. They could presumably get annual Pap smears, colonoscopies (for those over 50 without a family history of colon cancer), mammograms and other screenings that could detect anything unusual -- a precancerous lesion, for example -- well before it progressed to cancer.

The researchers looked at the histories of these Kaiser members from 1996 -- the first year HAART was available -- to 2007. Participants were 90% male, 55% white, 19% black and 21% Latino. Of the men, 74% were infected with HIV through sexual contact with another man, 16% through sexual contact with a woman, and 8% through injection drug use.

Among the men, at some point 552 had an ADC, 221 had an infection-related NADC and 388 had an NADC unrelated to another infection. A majority of cancers (67%) seen in HIV positive members were related to an infectious cause, compared with only 12% in HIV negative people of similar sex and age. The HIV positive participants also had a 30% increased risk of NADCs not caused by other infectious agents, compared with their HIV negative counterparts.

The researchers noted in the journal AIDS that almost 70% of cancers in HIV positive people were either AIDS-defining or related to infections -- mainly human herpesvirus 8 (the cause of KS), HPV and hepatitis B and C (which can cause liver cancer). They suggested that immunodeficiency reduces the body's ability to suppress oncogenic viruses.

The Kaiser study was limited in that it did not account for cancer risk factors such as smoking -- which is well known to cause lung cancer and can amplify the effects of HPV. The study also did not examine alcohol use, which is linked to cancers of the larynx and liver. Given the high rates of smoking and alcohol use among people with HIV, these omissions represent serious limitations.

Nevertheless, this study is notable for its long follow-up period, given the fact that most earlier research compared rates and risks of cancer among HIV positive people before and only shortly after the start of the HAART era. In spite of its limitations, the Kaiser study may give a more accurate snapshot of today's cancer risk for people with HIV in the U.S. -- at least men who have access to HAART and private health insurance. (Editor's note: See "Cancer and HIV/AIDS" in this issue for an overview of several recent studies of cancer in people with HIV.)