HIV-Related Anal Cancer: Incidence Rising Despite Effective Antiretroviral Treatment

Abstract & Commentary

By William B. Ershler, MD

Synopsis: Relative to the general population, the risk of anal cancer in HIV-infected patients remains very high. Unlike other malignancies associated with AIDS, effective antiretroviral treatment appears to have no preventive effect on anal cancer, particularly among men who have sex with men.

Source: Piketty C, et al. Incidence of HIV-related anal cancer remains increased despite long-term combined antiretroviral treatment: Results from the French Hospital Database on HIV. J Clin Oncol 2012;30:4360-4366.

The use of combination antiretroviral therapy (cART) to treat HIV infection has led to changes in the causes of death in HIV-infected individuals in industrialized countries.1-3 Over time, the risk that infected individuals will experience other comorbidities has increased. In this context, though the incidence of AIDS-defining malignancies (ADM) has declined, non-AIDS-defining malignancies (nADM) are now an important cause of mortality in HIV-infected individuals. The incidence of several nADMs is higher among HIV-infected individuals than among the general population. Furthermore, unlike what has been observed for ADM, several studies have assessed the standardized incidence ratio of nADM and have shown either no differences or even increased incidence of certain malignancies when comparing rates in the pre-cART era to more recent times.

Anal carcinoma is one nADM for which recent studies have indicated increasing incidence in HIV-infected individuals, particularly after the implementation of cART.4-6 To explore this within the French Hospital Database on HIV, Piketty and colleagues identified 263 cases of invasive anal squamous cell carcinoma confirmed histologically between 1992 and 2008. This nationwide hospital-based cohort includes 69 clinical and academic centers and comprehensive data on close to 110,000 patients with more than 700,000 person-years of risk.

The incidence rates of anal cancer across four calendar periods — 1992-1996 (pre-cART period), 1997-2000 (early cART period), and 2001-2004 and 2005-2008 (recent cART periods) — were determined as well as standardized incidence ratios (SIRs) comparing incidence in various HIV subsets and the general population by using incidence data from the French Network of Cancer Registries.

In HIV-infected patients, the hazard ratio (HR) in the cART periods vs the pre-cART period was 2.5 (95% confidence interval [CI], 1.28-4.98). No difference was observed across the cART calendar periods (HR, 0.9; 95% CI, 0.6-1.3). In 2005-2008, HIV-infected patients compared with the general population had an excess risk of anal cancer, with SIRs of 109.8 (95% CI, 84.6-140.3), 49.2 (95% CI, 33.2-70.3), and 13.1 (95% CI, 6.8-22.8) for men who have sex with men (MSM), other men, and women, respectively. Among patients with CD4 cell counts above 500/uL for at least 2 years, SIRs were 67.5 (95% CI, 41.2-104.3) when the CD4 nadir had been < 200/uL for more than 2 years and 24.5 (95% CI, 17.1-34.1) when the CD4 nadir was always above 200/uL.

Commentary

These results are consistent with those of prior reports indicating that the risk of invasive anal cancer is increased in HIV-infected individuals, not only in the pre-cART era but more recently as well.6-8 Further, relative to that in the general population, the risk of anal cancer in HIV-infected patients remains extremely high, even in patients with high current CD4 cell counts. cART appears to have no preventive effect on anal cancer, particularly in MSM.

One possible mechanism by which HIV infection would associate with increased rates of malignancy relates to the hypothetical acceleration of constitutional aging processes thought to occur with long-term infection HIV.9 In assessing this, Shiels and colleagues found that age at cancer diagnosis did not differ between HIV-infected patients and the general population for most cancers but notably did for both anal and lung carcinomas. The median age at diagnosis of anal cancer was found to be some 3 years younger in those infected with HIV (42 vs 45 years; P < 0.001).6

Thus, relative to the general population, the risk of anal cancer in HIV-infected patients remains extremely high, even in patients effectively treated with cART. Furthermore, with the aging of those living with HIV, it is likely that the prevalence of this once rare form of cancer will be increasing quite dramatically.

References

1. Lewden C, et al. Causes of death among human immunodeficiency virus (HIV)-infected adults in the era of potent antiretroviral therapy: emerging role of hepatitis and cancers, persistent role of AIDS. Int J Epidemiol 2005;34:121-130.

2. Mocroft A, et al. Changes in the cause of death among HIV positive subjects across Europe: Results from the EuroSIDA study. AIDS 2002;16:1663-1671.

3. Palella FJ, Jr., et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998;338:853-860.

4. Bower M, et al. HIV-associated anal cancer: Has highly active antiretroviral therapy reduced the incidence or improved the outcome? J Acquir Immune Defic Syndr 2004;37:1563-1565.

5. Diamond C, et al. Increased incidence of squamous cell anal cancer among men with AIDS in the era of highly active antiretroviral therapy. Sex Transm Dis 2005;32:314-320.

6. Shiels MS, et al. Age at cancer diagnosis among persons with AIDS in the United States. Ann Intern Med 2010;153:452-460.

7. Crum-Cianflone NF, et al. Anal cancers among HIV-infected persons: HAART is not slowing rising incidence. AIDS 2010;24:535-543.

8. Franceschi S, et al. Changing patterns of cancer incidence in the early- and late-HAART periods: The Swiss HIV Cohort Study. Br J Cancer 2010;103:416-422.

9. Bhatia R, et al. Accelerated aging and human immunodeficiency virus infection: Emerging challenges of growing older in the era of successful antiretroviral therapy. J Neurovirol 2012;18:247-255.