Non-AIDS cancers also more common in advanced HIV

Serious immune system suppression in people with HIV massively increases the risk of developing cancers not normally associated with HIV, according to research conducted in the United States.

A study recently published in the American Journal of Epidemiology, compared rates of cancer between the 122,993 AIDS patients in the State of New York and the general population of the State over the period 1981-1994. It found that not only do people with HIV run a greater risk of developing the AIDS-defining cancers Kaposi's sarcoma, non-Hodgkin's lymphoma and invasive cervical cancer, as expected, but that people with immune suppression caused by HIV also run a significantly higher risk of developing certain other cancers.

Brian Gallagher and his colleagues at the New York State Department of Health established that there were over 12,500 cases of cancer amongst people diagnosed as having AIDS in the period of the study. The most frequently observed cancers were those normally associated with severe HIV-related immune suppression, which occurred in massively increased numbers in people with HIV, with Kaposi's sarcoma being almost 100 times more likely to occur in men and 200 times more likely in women than in HIV-negative people. Similarly, non-Hodgkin's lymphoma was a little over 37 times more common in men with HIV than the general population and just under 55 times times more likely to occur in HIV-positive women than in HIV negative women.

Moreover, the New York team also established that people with HIV were on average three times more likely than the general population to develop other forms of cancer which are not normally associated with HIV.

Non-AIDS related cancers with a significantly elevated relative risk compared with the general population

• tongue (male, 1.8 relative risk; female, 7.1 RR);
• gum and other mouth (male, 1.9 RR; female, 11.1 RR);
• rectum, rectosigmoid and anus (male, 3.3; female, 3.0)
• larynx (male, 1.9; female, 5.9);
• trachea, bronchus, and lung (male, 3.3; female, 7.5);
• skin, excluding Kaposi's sarcoma (male, 20.9; female, 7.5);

brain and central nervous system (male, 3.1; female, 3.4);

• Hodgkin's disease (male, 8.0; female, 6.4);,
• multi-myeloma (male, 2.7; female, 7.2).

Some of these cancers may be mis-classified however. The AIDS Cancer Match Register Study Group, reporting in the Journal of the American Medical Association earlier this year, suggested that skin and soft tissue cancers in AIDS patients may not be recognised as Kaposi's sarcoma by some cancer specialists, and this may partially account for the elevated risk of skin cancer and the gender difference seen in this study and others.

The evidence from New York also suggested that the instance of cancers amongst people with HIV varied according to exposure category and sex. Gallagher's team established that men who were infected with HIV by sex with another man had a significantly increased risk of cancer of the anus, brain, central nervous system and connective tissue, and that men infected because of intravenous drug use had higher rates of cancer of the trachea, bronchus, lungs and stomach. Heterosexually infected women were at a higher risk of developing cancers of the brain, central nervous system, digestive system and invasive cervical cancer, whilst women infected through injecting drug use stood a greater chance of cancers of the bronchus, lungs, oral cavity and pharynx.

The New York research was conducted using records from AIDS patients between 1981-1994, before treatment with combinations of antiretroviral drugs significantly reduced the incidence of illness and death in people with HIV. However there is concern amongst some clinicians that even though some people recover from severe immunosuppression caused by HIV they may still be vulnerable to developing various forms of cancer.

Commenting on the research Gallagher said: "Cancer is a high morbidity and mortality complication of HIV and evaluating HIV-infected patients for (non-AIDS-related) cancers is important." He added that HIV clinicians should closely monitor their patients for signs of malignancy and offer advice on aspects of behaviour and diet that could increase the risk of developing cancer. However, Gallagher and his team have admitted that the link between cancers and HIV is not fully understood.

The research confirms findings published earlier this year which showed an increasing rate of Hodgkins disease, lung cancer, testicular cancer, lip cancer, penile cancer and soft tissue cancers as individuals became more immunosuppressed. Of the non-AIDS related cancers, some are linked to the sexually transmitted infection human papilloma virus. The association between immunosuppression, lifestyle and testicular cancer is unclear, and the excess rate of lung cancer found by the AIDS-Cancer Match Registry was not confined to the most common smoking-related cancer of the lung, adenocarcinoma.

UK findings

Figures from the UK government show that within the general population cancer causes nearly 250,000 deaths a year, 24 percent of all mortality, with lung, prostate and bowel cancers the most common in men, and breast, lung and bowel cancers in women. Amongst the general population under 65 there is a one-in three chance of developing some sort of cancer in a lifetime.

A major cohort study at the Chelsea and Westminster Hospital is gathering data on the instance of cancers in people with HIV in the UK. Dr Mark Bower said that data collection on non-AIDS defining cancers was almost non-existent until recently, but "It`s our impression that the rate is somewhat higher. The rates of lung cancer and testicular cancer are higher".

He also cautioned that fears about an imminent increase in cancers among people with HIV should not be exaggerated.

"It's real, but there are other factors at play. All the lung cancers seen at the Chelsea and Westminster, for example, have appeared in heavy smokers who were of an age where such cancers are not unexpected".

A recent review of cancers in HIV-positive individuals in the UK and the Thames Cancer Registry for the South East of England found that of the non-AIDS-defining cancers, only Hodgkin’s disease and anal cancer occurred more frequently in people with HIV. Anal cancer was only seen more frequently in non-African men and women. See Cancers-overview on this site for more details of this study, and further information about cancers in HIV infection.

Dr Martin Fisher of the Claude Nichol Centre in Brighton said: "We haven't had any cancers of the mouth, lungs and stomach (other than those caused by KS or lymphoma) in the past five years." Although this embraces the period since the widespread use of HAART, he added "we've only ever seen a few non-AIDS-defining cancers here in Brighton so it's too soon to say if there's a trend. But it is encouraging that we have not (yet at least) seen an increase in anal cancers amongst gay men which we'd feared."

Dr Mark Bower said that 15 cases of anal cancer had been seen at the Chelsea and Westminster Hospital, but also noted that in white gay men, as distinct from other risk groups, cancers - including lymphoma - now tend to be the first AIDS-defining illness, regardless of whether people have been taking HAART or not. In other groups, such as renal transplant patients, the total duration of immunosuppression has been associated with the long term risk of developing various cancers, and it will be important for clinicians to be alert to atypical cancers in future, especially in those who experienced a long period of immune suppression in the past.