THE ROLE OF IMMUNOHISTOCHEMICAL MARKERS IN THE DIAGNOSIS OF CERVICAL DYSPLASIA

Immunohistochemical analysis is a pivotal diagnostic method for detecting precancerous lesions and cervical carcinoma by evaluating the expression of p16INK4a and Ki-67 biomarkers. The detection of these proteins in tissue samples enhances the accuracy of differential diagnosis, enabling the distinction between reactive changes and dysplastic or neoplastic processes, thereby optimizing therapeutic decision-making. Relevance of the topic. Cervical intraepithelial neoplasia (CIN) is a precancerous condition characterized by pathological alterations in epithelial cells. Without timely diagnosis and intervention, CIN may progress to invasive cervical carcinoma (ICC) [1]. Nearly all cervical cancer cases are associated with sexually transmitted human papillomavirus (HPV). According to the World Health Organization (WHO), cervical cancer accounts for over 300,000 deaths annually, with the majority occurring in low- and middle-income countries (e.g., India, Nigeria, Bangladesh) [2]. HPV is detectable in 99% of cervical cancer cases, with HPV subtypes 16 and 18 responsible for approximately 70% of these cases [3,4]. The interval of 10–20 years between the onset of precancerous cervical lesions (CIN) and the development of invasive carcinoma provides a critical opportunity for screening, diagnosis, and treatment of precancerous conditions. According to WHO estimates, 2022 saw approximately 20 million new cancer cases and nearly 10 million cancer-related deaths globally. Projections indicate that by 2050, the annual number of new cancer cases will rise to 35 million, reflecting a 77% increase compared to 2022 [5]. During wartime in Ukraine, an increase in cervical cancer incidence has been observed. Chronic stress, sleep disturbances, and exposure to airborne pollutants resulting from explosions may compromise immune function, creating favorable conditions for cervical carcinogenesis. The WHO underscores the importance of advanced diagnostic techniques, including immunohistochemistry, in the global strategy for cervical cancer prevention and control. Conventional cytological methods (Pap test) and histopathological examination do not always provide definitive conclusions regarding the grade of cervical intraepithelial neoplasia or its risk of progression. The diagnosis of intraepithelial neoplasia is highly dependent on subjective factors, including the physician’s expertise, sample quality, and technical aspects of tissue processing, which may contribute to misinterpretation of cytological and histological findings. Immunohistochemistry plays a crucial role in the diagnosis and risk stratification of cervical dysplasia, holding substantial clinical, scientific, and societal relevance. This method improves diagnostic precision, facilitates personalized treatment strategies, and contributes to reducing cervical cancer-related mortality. Immunohistochemical analysis of the tumor suppressor protein p16INK4a (cyclin-dependent kinase inhibitor 4A) enables the identification of neoplastic foci, delineation of tumor margins, and correlation between its overexpression and the severity of epithelial abnormalities. Another key marker is the nuclear proliferation antigen Ki-67, which is expressed during active cell cycle phases (G1, S, G2, and M), serving as an indicator of cellular proliferation [8]. Thus, immunohistochemistry is an essential component of contemporary diagnostic and management protocols for cervical pathology. This review examines well-established biomarkers with proven diagnostic utility in cervical precancerous lesions. Objective: To evaluate the role of immunohistochemical analysis in diagnosing cervical intraepithelial neoplasia, based on current medical literature, and to emphasize the diagnostic significance of immunohistochemical markers (p16 and Ki-67) in differentiating grades of dysplasia. Furthermore, this study assesses the prognostic value of these markers in predicting the risk of malignant transformation in cervical epithelial cells. Conclusion. Immunohistochemical analysis is pivotal in the diagnosis and prognostic assessment of cervical pathologies, enabling accurate grading of dysplasia and estimation of its progression risk to invasive carcinoma. The p16 and Ki-67 biomarkers demonstrate high sensitivity and specificity in detecting cellular abnormalities associated with the persistence and integration of human papillomavirus.