Key considerations for people living with HIV

The natural history of HIV infection has been greatly changed by the introduction of highly active antiretroviral therapy (HAART). As a consequence of improved immune function, the incidence of AIDS-defining cancers (ADCs), such as Kaposi’s sarcoma, non-Hodgkin’s lymphoma (NHL) and invasive cervical cancer, has significantly declined. On the contrary, non-AIDS-defining cancers (NADCs), such as hepatocellular carcinoma, anal cancer, lung cancer, colorectal cancer and Hodgkin’s lymphoma, have gradually emerged as a major fraction of the overall cancer burden1.

It can be observed 84% increase in rate of HIV-associated cancers (NADCs) in HIV-infected versus HIV-uninfected adults was observed in one cohort.  Cancer events, occured at similar ages compared to HIV–uninfected adults: 7-month decrease in mean age at diagnosis of HIV-associated cancers in HIV-infected versus HIV-uninfected adults [crude difference in age: 2.9 years, with adjusted mean difference in age of -0.57 years (95% CI: -0.93 to -0.21)] 2. The incidence of NADC in last ten years has been stable with an overall incidence of NADC of 5/1000 person-years [95% confidence interval 4.65, 5.31]). Significant predictors of poorer survival after diagnosis of NADC are lung cancer (compared to other cancer types), male gender, non-white ethnicity and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis are associated with improved survival3.

In the D:A:D Study3 (with 176.775 participants and 880 NADC events from 2004-2010) the three most frequent NADC were lung cancer (n = 140, 0.79/1000 PY), Hodgkin’s lymphoma (n = 112, 0.63/1000PY), and anal cancer (n = 79, 0.45/1000PY).

The reasons are still partially unknown. Some of the increased risk may be explained by a high prevalence of cancer risk factors, such as smoking, alcohol consumption, human papilloma virus (HPV) infection and hepatitis C virus (HCV) infection among HIV-infected people. The role of immunosuppression in the development of NADCs is controversial, as several studies have not found a clear-cut evidence of an association between the degree of immunosuppression and the development of NADCs. For example, Patel and colleagues found that the risk of developing colorectal cancer was significantly increased in the presence of a low nadir CD4 cell count; on the contrary, in other papers no association between the degree of immunosuppression and the development of NADCs has been described1.

Analogously, the impact of HAART is still not well defined. The use of HAART was associated with lower rates of NADCs in a study by Burgi, whereas the standardized incidence ratio (SIR) for NADCs was reported not to be decreased in the post-HAART era among patients enrolled in the Swiss cohort study. Future research should focus on the etiology of NADCs, in order to shed light on the pathogenesis of cancer and ultimately to work for prevention; moreover, additional studies should evaluate the best therapeutic approaches to NADCs and the impact of cancer screening interventions among HIV-infected people, in an effort to diagnose cancer at an earlier stage1.

This review will focus on the following NADCs that occur commonly among people living with HIV:

  • Lung cancer
  • Hodgkin’s disease
  • Anal cancer
  • Hepatocellular cancer (HCC)
  • Other cancers (with limited data available): colorectal cancer (CRC), breast cancer, prostate cancer, testicular germ cell cancers.

Patients with NADCs should be managed by oncologists and HIV providers together. The minimum number of patients that an HIV oncology service should manage has not been defined. Several studies and a Cochrane review have shown that the more HIV patients treated by a clinical centre, the better the outcomes. In line with national cancer waiting times, all patients with suspected cancers must be referred urgently and seen within 2 weeks of referral. Moreover, the NHS Cancer Plan sets out the goal that no patient should wait longer than 1 month from an urgent referral with suspected cancer, to the start of treatment4.

We suggest that careful attention to the drug interactions between cytotoxic chemotherapy and antiretroviral agents is needed, as well as focus on opportunistic infection prophylaxis.

References

  1. Pinzone MR, Fiorica F, Di Rosa M, et al., Non-AIDS-defining cancers among HIV-infected people. Eur Rev Med Pharmacol Sci. 2012 Oct;16(10):1377-1388.
  2. Althoff K, Wyatt C, Gibert C, et al. HIV-infected adults are at greater risk for myocardial infarction (MI), end-stage renal disease (ESRD), and non-AIDS-defining cancers, but events occur at similar ages compared to HIV–uninfected adults. Program and abstracts of the 20th Conference on Retroviruses and Opportunistic Infections; March 3-6, 2013; Atlanta, Georgia. Abstract 59.
  3. SW Worm, M Bower, P Reiss, et al. Non-AIDS defining cancers in the D:A:D Study - time trends and predictors of survival: a cohort study. BMC Infectious Diseases 2013, 13:471.
  4. British HIV Association Guidelines for HIV-associated Malignancies 2013. Version 1. 25 July 2013.