Bladder cancer occurring earlier in people with HIV, and cases more difficult to treat, French study finds

The frequency of bladder cancer is elevated in patients with HIV, investigators from Paris report in PLoS ONE. Although the malignancy was rare, it often presented in an aggressive form and was associated with poor outcomes. Bladder cancer among patients with HIV mainly involved male patients and occurred at a younger age (mid-50s) than would be expected in the general population. A systematic literature review identified a small number of additional cases of the malignancy in patients with HIV, and again the cancer mainly affected men in their 50s and was often aggressive.

“Our study shows that bladder cancer can occur in patients with HIV-infection although it remains a rare event,” comment the authors. “When accounting for the different age and sex structure of our cohort and of the general French population…we observed more cases of bladder cancers than expected.”

In France 22% of deaths in HIV-positive patients are due to non-HIV-related cancers. Bladder cancer is one of the most common cancers seen in the general population, but very few cases of the malignancy in people with HIV have been reported in the scientific literature.

Doctors at the Saint-Louis Hospital in Paris observed a few consecutive cases of bladder cancer in HIV-positive patients. This prompted them to design a retrospective study of the records of patients treated at the hospital’s HIV clinic between 1998 and 2013 to assess the prevalence of bladder cancer and its characteristics. They also conducted a systematic literature review to identify further cases of the cancer in HIV-positive patients.

The investigators examined the records of 6353 patients with HIV infection and 2200 bladder cancer patients who received care at their hospital. They identified 15 cases of the malignancy in patients with HIV, representing 0.2% of the entire cohort. The five-year prevalence was estimated at 128.1 per 100,000 persons. In men, the prevalence was 85 per 100,000 persons, similar to that in the general French male population (107 per 100,000 persons). However, after the investigators adjusted their data to take account of the differences in the age/sex structure of their patient cohort to the general French population, they found that the cancer occurred over three times as often among individuals with HIV (standard morbidity ratio, 3.44).

Most (73%) of the HIV-positive patients with bladder cancer were men. Median age at diagnosis of bladder cancer was 56 years, considerably younger than the average age of 72 years for men observed in the general population. Approximately two-thirds of cases involved current smokers. Smokers in the study had a lengthy smoking history or were heavy smokers - the median smoking exposure was 36 pack years. Smoking has been identified as the single most important risk factor for bladder cancer in the general population and is estimated to cause at least half of US cases of bladder cancer in men and up to a third of cases in women. Frequent exposure to chemicals used in industrial processes is the other major cause.

Over half (55%) had a previous AIDS diagnosis and the median nadir CD4 cell count was 195 cells/mm³. Most (86%) patients were taking ART and 64% had an undetectable viral load. Median CD4 cell count at the time bladder cancer was diagnosed was 506 cells/mm³.

The investigators were interested to note that six of the ten assessable patients had lesions associated with infection with human papillomavirus (HPV) – two cases of cervical cancer and four of anal warts.

In almost three-quarters (73%) of cases, the presenting symptom was haematuria (blood in urine). Histological investigations showed that 80% of cases involved transitional cell carcinoma, the most common form of bladder cancer. High-grade histology was found in eleven patients, and 47% had tumours that had spread to muscle. One case of HPV was detected by biopsy.

The one-year survival rate was 75%. Four patients died during follow-up (27%), and all the deaths were related to bladder cancer.

The systematic literature review identified a further 13 cases of bladder cancer in patients with HIV. These shared characteristics with the cases treated in Paris. Most (eleven) involved men, median age at cancer diagnosis was 55 years and most patients were receiving ART. Blood in urine was the most common presenting symptom (nine cases). High-grade tumours were present in nine patients and 46% of patients died within a median of eight months of follow-up.

“Our study and literature review showed that bladder cancers in HIV-infected patients share common characteristics with bladder cancers in non HIV infected individuals,” note the investigators. These include, “male sex predominance, higher prevalence of Caucasians, a high proportion of smokers, painless haematuria as the main presenting symptom.”

Despite these similarities, bladder cancer in patients with HIV was also associated with several unusual features:

• Younger age (the investigators were therefore concerned that frequency would increase as their cohort continues to age).
• Possible association with immune suppression
• HPV involvement
• High rate of aggressive tumours.

“Physicians in charge of HIV-infected patients should be aware that their patients, as they become older, face an increased risk of bladder cancer, especially those with a low nadir CD4 cell count, who smoke, and also potentially those with HPV infection,” conclude the authors. “Because bladder cancers in HIV-infected patients seem to be more aggressive, this diagnosis should be suspected in any patients with haematuria or dysuria and should prompt rapid urologic examination.”