People living with HIV at higher risk of cancers caused by smoking or viruses, but not all cancers

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The risk of cancer is increased twofold for people with HIV compared to individuals in the general population, Danish investigators report in the online edition of AIDS. But the increased risk was almost entirely due to higher incidence of smoking-related cancers and also malignancies caused by viral infections. The risk of other cancers did not differ between the people with HIV and people who did not have HIV.

“In the present study we found that the increased risk of non-AIDS cancer was largely confined to cancers associated with smoking and viral infections,” write the authors. “The risk of cancers that are not considered strongly related to smoking or viral infections did not differ between the HIV-infected and the background population, and the impact of immune deficiency was limited.”

Non-AIDS-related cancers are an increasingly important cause of serious illness and death among people with HIV. The exact causes are uncertain. However, possible explanations include high rates of smoking, a high burden of viral co-infections such as hepatitis C virus (HCV) and human papillomavirus and immune suppression caused by HIV.



Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

human papilloma virus (HPV)

Some strains of this virus cause warts, including genital and anal warts. Other strains are responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.


In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

Investigators from Denmark wanted to establish the proportions of cancers in people living with HIV attributable to smoking, viral infections, and HIV-related immune suppression.

They therefore compared the incidence of cancer between people with HIV and matched controls in the general population. Results were stratified according to smoking status and immune deficiency. Cancers were categorised as smoking-related, virus-related or 'other'.

The HIV-positive population consisted of 3503 individuals who received care between 1995 and 2011. Their average CD4 count at baseline was 450 cells/mm3. At the time of inclusion in the study, 77% were taking HIV therapy and, for 92% of follow-up time, the people with HIV were taking antiretroviral therapy.

The control population consisted of 12,979 individuals.

There were 157 cancer diagnoses among the people living with HIV compared to 255 diagnoses among the controls.

The overall incidence of cancer was twice as high in people with HIV compared to the controls (IRR = 2.0; 95% CI, 1.6-2.5).

The incidence of cancers related to viral infections was almost twelvefold higher in the HIV-positive population than in the HIV-negative controls (IRR = 11.5; 95% CI, 6.5-20.5). Incidence of smoking-related cancers was almost threefold higher among people with HIV (IRR = 2.8; 95% CI, 1.6-4.9). The risk of other cancers did not differ between the people living with HIV and the HIV-negative controls.

Incidence of smoking-related cancers associated with current smoking was significantly higher among the people living with HIV (IRR = 21.35; 95% CI, 2.88-158.5) than the controls (IRR = 4.12; 95% CI, 1.74-9.78).

For the people with HIV, a lowest-ever (nadir) CD4 count below 200 cells/mm3 was associated with a more than threefold increase in the risk of lung cancer (IRR = 3.54; 95% CI, 1.00-12.59). No patients with a nadir CD4 count above 200 cells/mm3 developed a smoking-related cancer.

Smoking-related and virus-associated malignancies accounted for 23% and 43% of cancers diagnosed in the HIV-positive population. Virological cancers were rare in the controls.

The fractions of all cancers in the HIV-positive population attributable to smoking and viral infections were 27% and 49%, respectively.

For cancer types considered associated with smoking, the proportion attributed to smoking was 91%. The proportion of virus-related cancers attributed to having HIV was also 91%.

For cancers not strongly related to smoking or viral infections, the proportion attributable to being HIV positive and immune deficiency were 0%.

“We found that HIV patients, with long term-engagement in care, had an increased risk of cancers that are considered strongly related to smoking and viral infections,” comment the authors. “They did not have increased risk of other cancers compared with the background population. We found no association between immune deficiency and non-virological cancers that are not strongly related to smoking.”


Helleberg M et al. Risk of cancer among HIV-infected individuals compared to the background population: impact of smoking and HIV. AIDS 28, online edition. DOI: 10.1097/QAD.0000000000000283, 2014.