Cervical preneoplasia biomarkers: a conundrum for the community based gynecologic surgical pathologist

The integration of high-risk (HR) human papillomavirus (HPV) in the cell genome is an essential step in the oncogenic pathway of lower ano-genital HPV-related squamous preinvasive and invasive lesions. The expression of HR-HPV surrogate biomarkers of HR-HPV integration by immunohistocytochemistry (IHC) serves as a diagnostic and/or a prognostic tool of cervical preinvasive lesions. IHC is claimed to decrease the interobserver variability in the diagnosis of histomorphologically equivocal lesions, and to be helpful in evaluating the potentiality of regression, persistence or progression. The most common biomarkers used in cervical pathology are p16(INK4a), Ki-67, the HPV capsid L1 antigen, and ProEXc. Critical review of the literature shows a great variability in the diagnostic accuracy, risk evaluation, and relative distribution of these biomarkers in low and high grade preinvasive lesions. Review of the literature suggests that currently dual IHC with p16 and L1 provide the best diagnostic and prognostic evaluation of lesions diagnosed histomorphologically as low and high-grade.