In situ hybridization (ISH) is the demonstration of specific genetic inform
ation within a morphologic context. For HPV, colorimetric ISH has the advan
tage that it can be applied to routine formalin-fixed paraffin embedded tis
sues. This conserves patient material and permits histologic selection of o
ptimal material for testing. ISH allows for precise spatial localization of
viral sequences within tissues. ISH also allows the integration status of
HPV to be determined. The major limitations of the method are the potential
for error in HPV typing because of probe cross-hybridization and relativel
y low sensitivity if the method is not fully optimized.