The advent of highly active antiretroviral therapy (HAART) has significantly reduced the
incidence of AIDS events, including AIDS-defining malignancies. Nevertheless, several cohort studies
conducted in the post-HAART period have reported an increasing risk of non-AIDS-defining
Overall, the potential mechanisms leading to an increased risk of developing NADCs probably involve
multiple known and unknown factors. In addition to ageing, chronic inflammation and ongoing
immune system dysregulation, other contributing factors are co-infection with potentially oncogenic
viruses (HBV, HCV, HPV, EBV) and high-risk behaviours such as tobacco smoking.
As a consequence of these risk factors, high standardized incidence ratios have been consistently reported,
mainly in cohort studies regarding smoking-related cancers (lung cancer, but also pharyngeal
and kidney cancer), due to the far more common cigarette smoking habit in the HIV-population.
Also in the setting of infection-related malignancies, the high frequency of liver cancer, as a consequence
of HBV and HCV co-infection is well known. Similarly, HPV infection accounts for the
higher risk of anal cancer. On the same line, Hodgkin lymphoma is more frequent in the HIV population,
due to the dysregulation and proliferation of EBV-infected lymphocytes.
Several studies addressed the direct relationship between immunosuppression and cancer progression,
showing that subjects with HIV infection experience higher cancer-specific mortality, as compared
to the general population, independently of cancer stage or cancer treatment.
In the HIV population, for many NADCs, the prognosis is still worse as compared to the general
population. However, an improvement has been reported over the last decades, mainly thanks to
more available and adequate treatment chances.