Biomarkers for biological agents

Biomarkers of exposure to biological agents have proved to be extremely useful in establishing causal associations between infections and human cancer, as well as in tracing the natural history of the relevant agents. This chapter will focus on biomarkers for biological agents currently recognized as causally associated with various human cancers after evaluation at the IARC. These are human papillomavirus (HPV), hepatitis B (HBV) and C virus (HCV) and Helicobacter pylori. A prototype of nucleic-acid-based biomarkers is detection of HPV DNA. It measures the presence of type-specific DNA at a given point in time. PCR-based assays are considered the method of choice for epidemiological investigations. The test requires collection of exfoliated cells or biopsies. Specimens can be kept stored at -20 degrees C for long periods of time. DNA degradation is low. Some of the limitations of the marker for cancer epidemiology lie in the fact that HPV DNA infections are often transient, especially in young women. In repeated measurements, HPV DNA may fluctuate, but the reasons for this are unknown. Antigens and antibodies from the HBV and HCV can be viewed as prototypes for serological biomarkers. For HBV, there are markers able to distinguish between past and persistent infections. HBV DNA detection in sera further refines the assessment of exposure. Standardized serological assays are available and widely used in developing countries. For HCV antibodies, serological assays are standardized and widely available. RNA detection in sera by PCR is under development. A limitation of the currently available assays is the type and subtype variation of HCV by geography, which requires further research and standardization. In low-risk populations, numerous false-positive results arise and confirmatory tests are required.