Prevalence of P16 Immunohistochemistry Positive Staining and Its Correlation to Clinical and Radiological Staging of Squamous Cell Carcinoma of the Cervix.

Abstract

Background: Cervical cancer is the fourth most common genital tract cancer and fourth common cause of death among the causes of neoplasm-related mortality in women worldwide. Squamous cell carcinoma is the most common type and constitutes about 90% of all pathological types of cervical cancer. Cyclin-dependent kinase inhibitor 2A (CDKN2A; p16) is a gene that is located on chromosome 9 that encodes a protein (P16) that inhibits cyclin-dependent kinases 4 and 6 which are inhibitors of retinoblastoma protein; the net result is reactivation of retinoblastoma protein and arrest of cell cycle in G1 phase. So, expression of p16 protein within cancer cell may denote good prognosis. The presence of a soft marker that can detect hidden advanced stages in apparently clinically and radiologically early resectable stages of cervical cancer and can replace life-threatening preoperative lymphadenectomy is of great importance. Is P16 protein which when expressed is associated with good prognosis in other cancer can be this soft marker?

Aim of the study: The aim of this study is to estimate the prevalence of cyclin-dependent kinase inhibitor 2A (CDKN2A; p16) immunohistochemistry positive staining in squamous cell carcinoma of the cervix and to correlate its positivity  to clinical and radiological disease stage.

Patients and methods: An analytical cross-sectional observational prospective and retrospective study was conducted on 60 invasive squamous cell cervical cancer patients from gyne-oncology unit at Al Shatby university hospital after taking a written consent and following approval by Alexandria medical school institutional ethics committee. Inclusion criteria included all patients with invasive squamous cell carcinoma of the cervix prospective and retrospective from January 2019 till June 2022 diagnosed by taking wedge, punch and cone biopsy followed by histopathological examination that confirmed the diagnosis and showed grading and types of squamous cell carcinoma. Clinical examination, vaginal ultrasonographic scanning, computerized axial tomography and magnetic resonance imaging were carried out to all cases, and data were recorded for clinical and radiological staging purposes. All data were collected, coded, tabulated and statistically analyzed to estimate the prevalence of p16 positivity in the study cases and to correlate its positivity with clinical and radiological disease stage.

Result: In relation to prevalence of p16 immunostaining, 34 cases (56.7%) were positive in comparison with 26 cases (43.3%) being negative. Considering correlation between early resectable stage and late nonresectable stage with P16 positive and negative staining, the result showed the following: 32 cases (53.3%) were resectable, 30 cases (88.2%) of them were P16 positive immunostaining compared to 2 cases (7.7%) being P16 negative immunostaining while nonresectable cases were 28 cases (46.7%), 4 cases (11.8%) only were P16 positive compared to 24 cases (92.3%) being P16 immunostaining negative, so most of early resectable stage cases were P16 positive immunostaining and most of late nonresectable stage cases were P16 negative immunostaining. There is a positive significant correlation between early resectable stage in relation to positive P16 immunostaining, and the same was present between late nonresectable stage and negative P16 immunostaining (p = 0.000).

Conclusion: The present study concluded that P16 positive immunostaining prevalence in cervical squamous cell carcinoma was 56.7% and its positive staining is highly correlated with early resectable clinically and radiologically disease stage.