First HIV, then cancer

As people with HIV live longer, they are developing cancers at higher rates than the general population
Bill Hall
Bill Hall has lived with HIV since 1986. Seven years ago, he learned he also has non-Hodgkin's lymphoma. Photo by Robert Hood / Fred Hutch News Service

Bill Hall had seen the grim photos in newspapers and magazines of gay men dying of AIDS. So when he tested positive for HIV in June 1986, he assumed he had been sentenced to death.

The next 10 years were a blur of visiting friends in the hospital and going to funerals. Hall outlived the members of four support groups. Then he began taking first the drug AZT and, after 1996, an antiretroviral cocktail that kept the virus in check.

He survived.

One day about seven years ago – after more than a decade on treatment – Hall was brushing his teeth in his Seattle apartment and saw a lot of blood in the sink. He went to the dental clinic at Harborview Medical Center, where the dentist took a biopsy of an abscess in his lower gum.

A few weeks later, he had a new diagnosis: non-Hodgkin’s lymphoma.

“I just sat there and zoned out. I don’t even remember walking home,” said Hall, now 62, recalling his shock at being handed what he thought was a second death sentence. “It was like when I found out I was HIV-positive.”

From the early days of the AIDS pandemic, non-Hodgkin’s lymphoma has been one of a trio of cancers known as AIDS-defining malignancies. It, a rare skin cancer called Kaposi’s sarcoma and, in women, cervical cancer, signaled that a person’s HIV infection had progressed to full-blown AIDS. People didn’t die of AIDS, per se. They died of one of these cancers or of infections like pneumocystis pneumonia and toxoplasmosis that took advantage of a weakened immune system.

What Hall didn’t know at the time of his new diagnosis is that even as cases of full-blown AIDS and AIDS deaths have dropped dramatically since the introduction of antiretroviral drugs, the association between HIV and cancer remains.

About 1 of 22 people with HIV will develop non-Hodgkin’s lymphoma by age 75, compared to about 1 in 143 for the general population, according to a new study published today in the journal Annals of Internal Medicine. About 1 in 23 will develop Kaposi sarcoma, compared to about 1 in 10,000 in the general population. (The study did not look at cervical cancer.)

It’s not just the traditional AIDS-defining cancers that people with HIV have to worry about. Roughly 1 in 29 people with HIV will develop lung cancer by age 75, compared with about 1 in 36 in the general population. Incidents of other cancers such as anal and liver cancers and Hodgkin lymphoma are also higher in people with HIV. And colorectal cancer incidence, while lower, is rising in people with HIV, according to the study by lead researcher Dr. Michael J. Silverberg of Kaiser Permanente Northern California.

“Pretty much across the board, cancer incidence was higher in HIV patients,” said Silverberg in a phone interview.

Good news, bad news for HIV and cancer

Funded by the National Institutes of Health, the study estimated the cumulative cancer incidence of nine common cancers in 86,620 people with HIV and 196,987 uninfected adults from 1996 – the year “everything changed,” Silverberg said – to 2009. It is not the first to find higher rates of cancer in people with HIV, but it is one of the largest studies, and its authors hope to give people with HIV and their healthcare providers clear guidance on what to be on the alert for and what steps to take to prevent and screen for cancer.

The participants, mostly men, took part in a longtime study called the North American AIDS Cohort Collaboration on Research and Design, which was the collective effort of more than 20 cohort studies in the United States and Canada and drew on patients being treated for HIV at Kaiser Permanente, U.S. Veterans Health Administration hospitals and others. Taking advantage of the fact that people joined the study at different ages, researchers were able to statistically estimate the cumulative cancer incidence, or lifetime risk, up to age 75.

To some extent and for some cancers, the news is partly good: People with HIV are living long enough to develop diseases that become more common as people age.

“With these effective therapies, HIV patients are living almost normal lifespans,” Silverberg said. “Before [1996], people were dying before they were old enough to get many of these of diseases.”

And while people with HIV are still at greater risk for the traditional AIDS-associated malignancies, cases have declined with the growing use of antiretroviral therapy. Not everyone with HIV in the study was on antiretroviral therapy, but the numbers rose from about 39 percent in the early years to 74 percent in 2005-2009.

In an ideal world, everyone with HIV would be diagnosed early and immediately put on antiretroviral therapy. In reality, HIV is asymptomatic for many years, and about 1 in 8 of the 1.2 million people infected with HIV in the United States are unaware of their infection, according to the U.S. Centers for Disease Control and Prevention.

For some cancers, the higher incidence may not be entirely related to HIV infection. People with HIV tend to smoke and drink more. And longer survival also means longer exposure to infections that can cause cancers, such as human papillomavirus, or HPV, which is associated with anal and cervical cancers, and hepatitis B and C, which can lead to liver cancer.

“It’s not good enough to make sure everybody gets on therapy,” Silverberg said. “There are also risk factors you have to control.”

That said, the immune system of a person with HIV, even on treatment, is not the same as that of someone who is uninfected.

“There’s still underlying damage to the immune system and underlying inflammation that’s causing these cancers,” Silverberg said. “Even in the treated person, there is still higher risk.”

Get on treatment – but quit smoking too

Dr. Jeffrey Schouten, senior staff scientist at Fred Hutchinson Cancer Research Center’s Vaccine and Infectious Disease Division and director of the Hutch-based Office of HIV/AIDS Network Coordination, agreed that cancer in people with HIV “is a major problem” due to an aging HIV population, cigarette smoking, co-infection with other viruses and other factors, some of which take decades to result in cancer.

“It reaffirms what we already knew about the high risk of cancers – lung, liver and anal cancers in particular,” he said. “We’ve known for some time that smoking cessation should be a high priority for our patients. This reinforces the need to make that viable.”

It also raises new research questions, such as whether people with HIV should be included in the high-risk groups for which regular computed tomography screening for lung cancer is now recommended. The answer to that is not as obvious as it might appear because their already higher rates of lung infections could lead to false positives, Schouten said.

But other steps are no-brainers: Get tested for HIV. Get on treatment early. Deal with other risky behaviors like smoking and get skin, colon and other already recommended cancer screenings.

Hall said that if he’d known about his higher risk of developing cancer, he might have been more attuned to changes in his health. He didn’t notice he was losing weight, for example, until a friend told him to buy a belt.

“It didn’t occur to me that rapid weight loss meant something was going on,” he said. “I would have been on the lookout for that.”

After his dental appointment, Hall was assigned to an oncologist at Harborview, who immediately told him that not all cancer is a death sentence. He underwent chemotherapy. Seven years out from his cancer diagnosis, he is doing well. Even his long-term depression is under better control as he’s become active in numerous organizations, including serving on the community advisory board of defeatHIV, a research group based at Fred Hutch that is investigating using gene-editing to cure HIV.

“I’m fine,” Hall said. “I never say I’m great because I do live with both diseases. But I’m actually doing quite well, considering. And I’m happy about that.”




Mary Engel is a former staff writer at Fred Hutchinson Cancer Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.

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