Being HIV-positive increases the risk of AIDS-related cancers such as Kaposi’s sarcoma (KS) and non-Hodgkin lymphoma (NHL), and extended survival since the advent of highly active antiretroviral therapy (HAART) in the late 1990’s also brings an age-related increased risk of other cancers.
In fact, as HIV-infected individuals age along with the rest of the country, they turn out to have about the same increased risk of non-AIDS defining cancers (NADCs) such as breast and prostate cancer as older people in general, notes Dirk P. Dittmer, PhD, professor in the department of Microbiology and Immunology at the University of North Carolina at Chapel Hill.
With a few tweaks in chemotherapy, HIV-positive individuals can be treated for cancer as effectively as anyone else, says Dittmer, who is also a researcher for the AIDS Malignancy Consortium.
“There’s no evidence that I am aware of that standard cancer treatments do not work on people who are HIV-positive when they stay on their antiretrovirals,” he adds. “There are some special considerations such as drug-drug interactions with ART and drug metabolism, but other than that the same therapies apply.”
A number of clinical trials are proving this point, and recent cancer statistics among the HIV population underscore the importance of these successes.
Cancer Burdens Rise and Fall
A new study by Dittmer and colleagues uses the UNC Center for AIDS Research HIV Clinical Cohort (an observational cohort of 3,141 patients receiving HIV care at UNC since 1996) and links it with the North Carolina Cancer registry to estimate cancer incidence rates from 2000 to 2011. Overall, the researchers identified 202 cancers across 15,022 person-years of follow-up, with 134 NADC cases and 68 AIDS-defining cancers (ADCs).
The highest incidence rates (per 100,000 person-years) among the HIV population:1
• KS: 213
• NHL: 226
• Anal cancer: 107
• Lung cancer: 146
Surprisingly, Dittmer notes, NHL appeared to decrease from 2000 to 2011 (a decline of 15 cases per 100,000 person-years per calendar year), while no other cancers showed changes in incidence or in incidence trends.
The most predominant NADC in the HAART era is lung cancer,2 largely due to smoking. It appears to increase over time in the UNC cohort (rising 8 cases per 100,000 person-years each year), but the trend is non-significant.
“What leaps out at us is the high incidence of anal cancers. This is very dramatic,” says Dittmer. “We have pap smears to screen for cervical cancer, but screening for anal cancer is not being done. It’s outside of general practice. So cervical cancer is rare, we see only two cases versus 16 for anal cancer.”
A majority (61%) of the cancers among the HIV positive population are virus-related:
• KS (n=32), caused by human herpesvirus 8.
• NHL (n=34), some cases of which are caused by Epstein–Barr virus.
• Anal cancer (n=16), often due to human papillomavirus (HPV)
• Cervical cancer (n=2), also caused by subtypes of HPV.1
The UNC data concurs with a larger 2011 report by the National Cancer Institute (NCI), tracking trends from 2004 to 2007 among the HIV population in 34 states via registries in the HIV/AIDS Cancer Match (HACM) Study.3 That report also shows KS to be the major ADC and lung cancer the predominant NADC.
While the NCI report shows a decline in ADCs, it also documents an increase in NADCs in the burgeoning over-40 HIV population. It calls the trend “a serious public health issue” needing “targeted cancer prevention and treatment strategies to reduce this burden.”
Chemo Works Despite HIV
Recent clinical trials attest to the success of chemotherapy in HIV-positive patients. “HIV does present some special problems, but they are not insurmountable," says Dittmer. "For example, drug-drug interactions between ART and chemotherapy drugs can be a concern.” says Dittmer.
Drug-drug interactions between ART and chemotherapy drugs can be a concern, for example. “A chemotherapy drug like rapamycin gets broken down in the liver," he says. "The cytochrome P450 enzyme breakdown pathway is inhibited, so you give 1/20th of the dose. But with nonnucleoside reverse transcriptase inhibitors (NNRTIs), you need to give more.”
He cites a small 2012 AIDS Malignancy Consortium clinical trial, conducted at New York’s Memorial Sloan-Kettering Cancer Center, which investigated rapamycin interactions in seven KS patients on either protease inhibitor (PI)-containing or NNRTI-containing ART regimens.
Among the participants (4 on PI-based and 3 on NNRTI-based ART), there were no significant changes in viral loads, and only modest initial decreases in CD4 counts occurred in some patients. Three participants, all on PI-containing regimens and with higher rapamycin exposure, showed partial KS responses, Dittmer and co-investigators report in the Journal of Acquired Immune Deficiency Syndrome.4
While pharmacokinetic interactions were seen (>200-fold differences in cumulative weekly rapamycin doses between participants on PI-containing and those on NNRTI-containing regimens), he points out that the drug could be used to advantage. “With cancer therapy, your white blood cells get wiped out, including the T cells, which are fast-growing and are the same cells targeted by HIV,” Dittmer observes. “So if anything, chemotherapy will reduce the number of HIV-infected cells. All cancer drugs kill those cells. There’s no extra risk, if it’s properly managed.”
Another consortium trial, a pilot study of paclitaxel (also broken down by CYP450) in 34 advanced KS patients, showed that despite the need for higher drug exposure in those on PI drugs, there was no toxicity and 30% of patients had an objective response.5
Barriers to Care
Often the biggest barrier to treatment is just being HIV-positive -- which is among the exclusions in clinical trials of cancer drugs, Dittmer notes. The result is that the most effective drugs are often not available because they have not been tested in the HIV population.
Studies show other disparities in care. HIV-infected individuals are at higher risk for lung cancer and for higher mortality following cancer diagnosis than HIV-uninfected individuals.6
Yet a 2013 study of almost 157,000 HIV-positive adults reported to the Texas Cancer Registry from 1995 to 2009 shows that HIV-infected patients who have non-small cell lung cancer (NSCLC) patients receive cancer treatment less frequently than their HIV-negative counterparts (60.3% vs. 77.5%, respectively). HIV infection was associated with higher lung cancer-specific mortality and more strongly associated with mortality among untreated than among treated patients, even after adjusting for sex, race, stage, and histologic subtype. However, inclusion of cancer treatment in adjusted models slightly attenuated the effect of HIV on lung cancer-specific mortality.7
HIV-positive NSCLC patients also tended to be younger, non-Hispanic black men, with distant disease.
Awareness and Screening
As with non-HIV populations, cancer screening and prevention are key to reducing the incidence and risk of cancers among HIV-infected individuals. Primary care physicians should screen not lonly for anal cancer but also for breast, prostate, and cervical cancers, Dittmer advises, and should be aware of the possibility of lung cancer among HIV-positive individuals. As to the latter, of course, smoking cessation is crucial for prevention.
“There’s no great difficulty in treating HIV-positive people with cancer, with some slight adjustments in treatment," he says, “HIV-positive people now have same lifespan as negatives. With proper treatment for cancer, that can still be true.”
For further information, Dittmer advises physicians to contact the AIDS Malignancy Consortium.
1. Yanik EL, Tamburro K, Eron JJ et al. Recent cancer incidence trends in an observational clinical cohort of HIV-infected patients in the US, 2000 to 2011. Infect Agent Cancer (2013) 8:18. doi:10.1186/1750-9378-8-18
2. Mani D, Haigentz M Jr, and Aboulafia DM. Lung Cancer in HIV Infection. Clin Lung Cancer (2012) 13:6-13. doi: 10.1016/j.cllc.2011.05.005. Epub 2011 Jul 29.
3. Shiels MS, Pfeiffer RM, Gail MH, et al.Cancer burden in the HIV-infected population in the United States J Natl Cancer Inst (2011) 103:753–762 doi: 10.1093/jnci/djr076
4. Krown SE, Roy D, Lee JY, et al. Rapamycin with antiretroviral therapy in AIDS-associated Kaposi sarcoma: an AIDS Malignancy Consortium study. J Acquir Immune Defic Syndr (2012) 59:447-454. doi: 10.1097/QAI.0b013e31823e7884.
5. Cianfrocca M, Lee S, Von Roenn J, et al.Pilot study evaluating the interaction between paclitaxel and protease inhibitors in patients with human immunodeficiency virus-associated Kaposi’s sarcoma: an Eastern Cooperative Oncology Group (ECOG) and AIDS Malignancy Consortium (AMC) trial. Cancer Chemother Pharmacol (2011) 68:827-833.
6. Cadranel J, Garfield D, Lavolé A, et al. Lung cancer in HIV infected patients: facts, questions and challenges. Thorax (2006) 61:1000–1008. doi: 10.1136/thx.2005.052373.
7. Suneja G, Shiels MS, Melville SK, et al Disparities in the treatment and outcomes of lung cancer among HIV-infected individuals. AIDS (2013) 27:459-68. doi: 10.1097/QAD.0b013e32835ad56e.