Clinical human papillomavirus testing modalities: Established techniques and new directions

Testing for the presence of human papillomavirus (HPV) has important implications for the identification of women at increased risk of developing cervical cancer. Signal amplification and polymerase chain reaction-based molecular tests have demonstrated an extremely high sensitivity for the detection of the HPV genome but suffer from a low specificity for high-grade disease that requires treatment. New molecular tests designed to target the activity of HPV in the cell, including assays for HPV gene products E6, E7, and L1, as well as the cell cycle protein p16^INK4A, have been developed with the hope of overcoming this problem. Immunocytochemical tests that use markers to detect the activity of HPV in the cell, particularly p16 ^INK4A, have been studied but are only rarely used clinically in cytology. A novel antibody directed against L1 and a combination of antibodies against minichromosome maintenance protein-2 and topoisomerase IIα both show promise and may lead to expanded use of this approach for HPV-related testing.