HIV-positive men have an increased risk of developing testicular cancer, according to a study published in the May 15th edition of the Journal of Clinical Oncology. The study also found that although the incidence of testicular cancer has not fallen since the introduction of HAART, HIV-positive men are just as likely as those without HIV infection to have the malignancy successfully treated.
There is conflicting evidence about the incidence and outcome of testicular germ cell tumours (GCT) in HIV-positive men, with a number of small studies reaching opposing conclusions. In addition, little is known about the long-term prognosis of HIV-positive men with GCTs as most of the studies were conducted pre-HAART.
Investigators at five UK HIV treatment centres and one in Denmark collaborated on a study to try and establish the course of GCT in HIV-positive patients and the effects of HAART on the incidence and outcome of GCT. Incidence was calculated using the Chelsea and Westminster Hospital’s prospective cohort of 8,640 HIV-positive men who have contributed over 42,000 patient years of follow-up. This incidence was then compared to age matched HIV-negative men in south east England.
There are two types of GCT: seminoma which are considered less aggressive and non-seminomatous GCT’s (NSGCT).
A total of 35 cases of GCT were identified between 1985 and 2001 at the six clinics. All but three cases involved gay men, and the average period between HIV diagnosis and the diagnosis of GCT was 4.2 years (range zeo to 14 years). Most cases of GCT – 22 - were diagnosed before effective anti-HIV therapy became available, with the remaining 13 cases diagnosed since 1996.
Nearly two thirds (n=26, 74%) of patients were diagnosed with seminomas. The remaining nine men had the potentially more aggressive NSGCT form of testicular cancer. Age and CD4 cell count were comparable between both patient groups.
Patients were monitored for an average of 4.6 years after the diagnosis of testicular cancer (range 0.3 to 14 years). In total ten patients died, three from GCT and seven from HIV-related disease. All the HIV-related deaths occurred before treatment with HAART became available.
The investigators calculated overall five year survival to be 79% (95% CI, 66% - 94%) and tumour free survival to be 89% (95% CI, 77% to 100%).
Chemotherapy was provided to 17 patients, and ten reported moderately severe or worse side-effects. However, no patient developed a secondary malignancy after chemotherapy. Chemotherapy did however result in a fall in CD4 cell count from an average of 315 cells/mm3 to 227 cells/mm3, and radiotherapy a decline in CD4 cell count from 343 cells/mm3 to 233 cells/mm3. Two patients developed AIDS-defining opportunistic infections during chemo or radiotherapy.
Incidence
Using the 8,600 male patients in the Chelsea and Westminster cohort, the investigators calculated that the incidence of GCT in HIV-positive men was 3.32 per 100,000 patient years of follow up (95% CI, 1.82 – 5.57). This was significantly higher than that for age matched HIV-negative men in south east England (0.76 per 100,000 patient years; 95% CI, 0.67 – 0.85, p<.01>
Seminomas occurred with significantly greater frequency in age-matched HIV-positive men (RR 5.45, 95% CI, 3.35 – 8.10), but this was not the case for NSGCT.
The incidence of GCT did not decline with the advent of HAART with an incidence of 4.0 per 100,000 patient years of follow-up prior to 1996 and 3.7 per 100,000 patient years of follow-up after.
Chronic immune suppression is thought by the investigators to be the most likely cause.
Conclusions
”This study found no difference when the incidence of HIV-related GCT was compared in the pre- and post-HAART era,” note the investigators, adding, that “if a number of years of chronic immune suppression are required for HIV-related GCT to develop, an increase in incidence may become apparent only with prolonged follow-up.”
Treatment with HAART should be maintained in patients receiving even the most aggressive therapies for GCT, “because the cancer is associated with an excellent overall survival.”
The investigators conclude that increased incidence of GCT is seen in HIV-positive men. This is likely to be due to chronic immune suppression, and as HAART has resulted in people with long-term immune suppression living longer, the incidence of GCT is likely to increase even further over the coming years.
Further information on this website
AIDS deaths down, but new causes of death at largest UK HIV clinic - news story, April 2003
No higher risk of non-AIDS cancers in advanced HIV disease, says US National Cancer Institute - news story, April 2003
Non-AIDS cancers more common in advanced HIV disease - news story, October 2001
Powles T et al. Multicenter study of human immunodeficiency virus-related germ cell tumours. Journal of Clinical Oncology 21: 1922 – 1927, 2003.