Table 3.

Biomarkers in cervical dysplasia

Biomarker	Significance
L1 capsid protein	Represents approximately 90% of the total protein on the virus surface and is generally detectable during the reproductive phase of HPV infection. The L1 protein is abundant in productive infections (CIN 1), found only in rare cases of CIN2/3, and not produced in carcinomas
p16INK4a (CINtecTM)	Surrogate marker of HPV E7-mediated pRb catabolism, providing evidence of transformation of the cervical mucosa. On immunohistochemistry, diffuse staining for p16INK4a is present in almost all cases of CIN2, CIN3, squamous cell carcinoma and endocervical glandular neoplasia; however, it is rarely detected in benign squamous mucosa or CIN 1 lesions caused by low risk HPV types
Ki-67	Proliferation marker confined to the parabasal cell layer of normal stratified squamous mucosa but shows expression in the stratified squamous epithelium in CIN lesions in correlation with the extent of disordered maturation, but cannot discriminate HPV-mediated dysplasia from proliferating cells in benign reactive processes
DNA Aneuploidy	HPV infection leads to DNA hypermethylation, disruption of the normal cell cycle, and chromosomal aberrations, all of which may lead to changes in DNA content. Aneuploidy increases progressively from CIN1 to CIN3
MCMs (ProExC testTM)	MCMs are required for the origination of DNA replication and are overexpressed in cervical high-grade dysplasia and carcinoma, but can also be seen in some benign cycling squamous and glandular cells
FISH technology	One of the most consistent chromosomal abnormalities in cervical carcinoma is gain of chromosome arm 3q (in about 70%), which can be detected by FISH. TERC gene in this region is amplified in progression to CIN3

FISH: Fluorescent in situ hybridization; MCAs: Minichromosome maintenance proteins; TERC: Telomerase RNA component.