Currently, Hodgkin’s disease (HD) is not considered an AIDS-defining cancer. However, those infected with HIV are 7.6 to 11.5 times more likely to have HD compared to the general population. Some report that HD is the most common non-AIDS-defining malignancy among HIV-positive people; however, other studies cite lung cancer as the most common.
Some researchers feel strongly that HD should be considered an AIDS-defining condition,3 though this issue is controversial. While analyses have routinely demonstrated increased risk of HD in those infected with HIV, an actual causal link between HIV and HD has not been established and studies assessing the effect of immune-suppression on incidence of HD are conflicting.
A positive correlation between immune-suppression and increased incidence of HD has been demonstrated in some analyses, but not others. Additional evidence indicates that HD tends to occur early in HIV infection when CD4 T cell counts are higher and immune competence is still intact, indicating that HD is not a critical event in the development of AIDS.
Few studies have looked at the effect of HAART on incidence of HD. However, those that have assessed this relationship reported no difference in rates either when comparing patients who had received HAART with treatment-naïve patients or when comparing HD rates during the pre-HAART and post-HAART eras.
Similar to cervical cancer, anal cancer is strongly associated with HPV infection and the presence of precancerous anal lesions, which are referred to as squamous intraepithelial lesions (SIL) and anal intraepithelial neoplasia (AIN).
High-grade forms of these lesions tend to contain the oncogenic types of HPV, specifically HPV-16 and HPV-18. Most studies demonstrate that those infected with HIV are 30 to 50 times more likely to have anal cancer, with rates as high as 60 fold in HIV-positive men who are bisexual or homosexual.
Progression to high-grade dysplasia is increased in the presence of HIV infection, and anal HPV infection and high-grade SIL (HSIL) are extremely common in bisexual and homosexual men, regardless of HIV sero-status.
Until recently, anal sex was assumed to be the mode of acquisition for anal HPV infection. However, when rates of HPV infection and SILs were compared in HIV-positive men with or without a history of bisexual or homosexual behaviour, rates were high even in those men with no history of anal sex who contracted HIV through IV drug use.
These data suggest that anal HPV infection can be acquired through means other than anal intercourse in HIV-positive men. Moreover, 76% of HIV-positive women and 42% of high-risk HIV-negative women tested positive for anal HPV DNA.
Presently, it is unclear whether prevalent risk factors, such as anal intercourse, a history of sexually transmitted diseases, or even heavy tobacco use are responsible for the increased incidence of anal cancer in the HIV-positive population.
An alternative hypothesis is that HIV-induced immune-suppression results in the development of anal neoplasia and, consequently, anal cancer. Incidence of anal SIL is highest among the most immune-suppressed HIV-positive men.
Moreover, regression of lesions is associated with high CD4 T cell counts at the time of HAART initiation, and HIV-positive men who progress have the lowest CD4 T cell counts.
However, other analyses have failed to show a clear relationship between CD4 T cell counts and incidence of anal cancer. In addition, one study revealed that incidence was significantly increased even during early HIV infection, suggesting that severe immune-suppression is not necessary for the development of anal cancer.
The possible benefits of HAART on the incidence of anal cancer and precancerous lesions have not been conclusively demonstrated. The few studies that have examined this relationship suggest that HAART has not decreased the incidence or increased the regression of these lesions.
When rates during the pre-HAART and post-HAART eras were compared, no significant change in incidence of anal cancer was observed; however, researchers pointed out that there were too few cases from which to draw definitive conclusions.
People infected with HIV are 2.5 to 7.5 times more likely to develop lung cancer compared to HIV-negative people. In fact, lung cancer was the most frequently observed non-AIDS-defining malignancy in several studies.
Lung cancer was the most common cause of death from a non-Aids-defining malignancy in persons with Aids in San Francisco between 1994 and 1998.
However, another study failed to demonstrate a significant increase in lung cancer incidence in the HIV-positive population. Several studies have reported a positive correlation between rates of lung cancer and immune suppression.
Analyses of risk behaviour have reported conflicting data: one study showed that HIV-positive patients with lung cancer smoked twice as many cigarettes as HIV-negative patients with lung cancer, while another study that compared HIV-positive women to HIV-negative women with similar smoking histories showed a two-fold increased incidence in the HIV-positive women.
Long-term cigarette exposure is typically lower in HIV-positive patients because they are usually diagnosed with lung cancer at an earlier age. Before the introduction of HAART, rates of lung cancer were low, perhaps on account of early AIDS-related mortality. A recent analysis showed an almost 9-fold increase in lung cancer incidence following the introduction of HAART.
Testicular Germ Cell Tumours
Testicular cancer (also referred to as testicular germ cell tumours or GCTs) is the most common solid malignancy in men between the ages of 15 and 34 years in the general population.
Studies assessing cancer incidence demonstrate that HIV-positive men are 1.4 to 8.2 times more likely to develop testicular cancer, though another study failed to show significantly increased incidence.
While no viral oncogene has been implicated in HIV-associated testicular cancer, viruses such as mumps orchitis, HPV, Epstein-Barr virus (EBV), and human endogenous retrovirus K10 are associated with testicular cancer in HIV-negative men and may be involved in development of testicular cancer in the HIV-positive population.
One large study reported a modest association between incidence of seminoma GCT and immune-suppression. However, another analysis showed that HIV-positive patients with seminoma appeared to have preserved immune systems The effect of HAART on incidence rates has not been analyzed thoroughly, but one report showed no difference in incidence rates when comparing the pre-HAART and post-HAART eras.
(Additional information from various sources)