Dysplasia and cancer screening in 21st century

Cancer is the second leading cause of death in the United States, and is projected to overtake cardiovascular diseases as the number one cause of mortality in adults within a decade. Cancer screening offers an opportunity to detect cancer precursor lesions at early stages, and hence preemptively manage and prevent development of frank cancers. Despite tremendous technological advances over last decade, which allow us to study genomic/epigenomic and proteomic profile of cells with unprecedented details, it has been difficult to develop non-invasive biomarkers with high sensitivity and specificity that can have clinical applications. Dysplasia, which requires histopathological examination of the tissue, remains the best marker of propensity to develop cancer, and hence the best available surrogate biomarker. However, procuring tissues for detection of dysplasia is highly invasive and economically unviable for most visceral malignancies. Therefore, there is emphasis on developing circulating biomarkers through a consortium approach where high-performing biomarkers in basic research are tested in large collaborative clinical settings to assess their clinical efficacy. In this review, we have discussed fundamental principles of cancer screening, difficulties in developing novel and effective biomarkers, continuing reliance on dysplasia as best available surrogate marker for cancer screening, as well as briefly highlighted newer screening modalities.