Biomarkers in Cervical Squamous Neoplasia: Diagnostic, Prognostic, and Predictive

Cervical squamous neoplasia runs the gamut from low-risk intraepithelial processes to aggressive invasive malignancies. A variety of biomarkers can be enlisted to help diagnose, prognosticate, and inform treatment of these lesions. There are ongoing controversies about diagnostic and prognostic biomarker use in squamous intraepithelial lesions, and many pathologists are new to predictive biomarker interpretation in invasive cervical lesions.

To provide practical guidance on the appropriate use of diagnostic, prognostic, and predictive biomarkers in cervical squamous intraepithelial lesions and invasive carcinomas.

Peer-reviewed literature and the author's personal experience.

Diagnostic biomarkers such as p16 and human papillomavirus E6/E7 messenger RNA in situ hybridization can have value in the diagnosis of squamous intraepithelial neoplasia, but there are important caveats to their use and interpretation. No prognostic biomarkers have yet demonstrated statistically durable significance for risk stratification of low-grade squamous intraepithelial lesions. Programmed death ligand-1 immunohistochemistry and tumor mutational burden testing are US Food & Drug Administration-approved predictive biomarkers that can be enlisted for the identification of invasive cervical squamous carcinomas that may respond to checkpoint inhibitor-based immunotherapy, whereas human epidermal growth factor receptor 2 (HER2) immunohistochemistry can identify optimal candidates for conjugated anti-HER2 therapies.