The clinical impact of using p16^INK4a immunochemistry in cervical histopathology and cytology: An update of recent developments

Abstract

Cervical cancer screening test performance has been hampered by either lack of sensitivity of Pap cytology or lack of specificity of Human Papillomavirus (HPV) testing. This uncertainty can lead to unnecessary referral and treatment, which is disturbing for patients and increases costs for health care providers. The identification of p16 INK4a as a marker for neoplastic transformation of cervical squamous epithelial cells by HPVs allows the identification of HPV-transformed cells in histopathology or cytopathology specimens. Diagnostic studies have demonstrated that the use of p16 INK4a immunohistochemistry substantially improves the reproducibility and diagnostic accuracy of histopathologic diagnoses. p16 INK4a cytology has substantially higher sensitivity for detection of cervical precancer in comparison to conventional Pap tests. Compared to HPV DNA tests, immunochemical detection of p16 INK4a -stained cells demonstrates a significantly improved specificity with remarkably good sensitivity. About 15 years after the initial observation that p16 INK4a is overexpressed in HPV-transformed cells we review the accumulated clinical evidence suggesting that p16 INK4a can serve as a useful biomarker in the routine diagnostic work up of patients with HPV infections and associated lesions of the female anogenital tract.

Interobserver reproducibility and accuracy of p16/Ki‐67 dual‐stain cytology in cervical cancer screening

“…[4][5][6] It is a marker for HPV-related transformation that highlights disruption of the retinoblastoma (RB)/E2F pathway related to activity of HPV oncogene E7. 7 Although p16 expression is strongly related to HPV oncogene activity, it is also observed physiologically in some metaplastic cervical cells.…”

p16INK4a/Ki‐67 co‐expression specifically identifies transformed cells in the head and neck region

“…4,5 By analogy, p16 INK4a immunohistochemical overexpression also indicates HPV-induced HNSCC with overall high sensitivity and specificity, particularly within the oropharynx. [6][7][8][9] However, some central aspects impede the unrestricted diagnostic use of p16 transformation in the head and neck.…”

Survey of p16INK4a immunohistochemistry in diagnosis of dysplastic changes in cervix

“…1,5 Women with abnormal screening test results for cervical cancer are commonly referred to colposcopy after some triage test. 6 Cyclin dependent kinase (CDK) inhibitor 2A also known as p16 INK4a limits cell cycle through negative feedback control to check the cell proliferation by regulation of CDK4 and CDK6. Thus, in the cervical neoplasia and dysplasia, the overexpression of p16 INK4a happens.…”

“…Thus, in the cervical neoplasia and dysplasia, the overexpression of p16 INK4a happens. 7 6 The present study aimed to evaluate p16 INK4a immunohistochemical staining for diagnosis of CIN in patients who had definite histopathological diagnosis with low and high-grad cervical lesions.…”