Cancer biomarkers in HIV patients

Abstract

Purpose of review: In this review, we update investigations related to cancer biomarkers in HIV-infected populations.

Recent findings: CD4 lymphocyte count is associated with primary central nervous system lymphoma (PCNSL), systemic non-Hodgkin's lymphoma (NHL) (except perhaps for Burkitt lymphoma), Kaposi's sarcoma, cervical cancer, and anal cancer. HIV load is associated with Burkitt lymphoma and systemic NHL (but not PCNSL), with Kaposi's sarcoma and with anal cancer. CD40 ligand incorporated into the HIV envelope and expression of activation-induced cytidine deaminase may help explain the relationship between HIV load and Burkitt lymphoma. Genetic polymorphisms have been identified that are linked to lymphoma in HIV patients. B-cell activation as manifest in immunoglobulin light chain production may be an important marker for NHL risk. Cytokines and related molecules (IL10, sCD30) may identify patients at high risk for NHL. Epstein-Barr virus (EBV) in cerebrospinal fluid (CSF) is useful as a marker for PCNSL, although with the falling incidence of PCNSL, the specificity of the test has been called into question. EBV and Kaposi's sarcoma-associated herpesvirus (KSHV) have not yet emerged as especially promising markers of risk for either lymphoma or Kaposi's sarcoma.

Summary: CD4 lymphocyte count, HIV load, germline genetic polymorphisms, cytokine and related molecules, and immunoglobulin light chains all show increasing promise as biomarkers of malignancy in HIV patients.

Fig 1

Non-Hodgon’s lymphoma (NHL) risk as a function of serum free light chain (FLC) levels among HIV-infected people. Odds ratios (ORs) and associated 95% CIs are presented for NHL in relation to FLC levels. FLC levels are categorized as normal or as a multiple of the upper limit of normal (ULN). ULNs are l.94 mg/dL for κ and 2.63 mg/dL for λ. The panels correspond to results for (A) κ FLC levels measured 0 to 2 years prior to NHL diagnosis/control selection: (B) κ FLC levels measured 2 to 5 years prior to NHL diagnosis/control selection; (C) λ FLC levels measured 0 to 2 years prior to NHL diagnosis/control selection; and (D) λ FLC levels measured 2 to 5 years prior to NHL diagnosis/selection.