Histopathological Verification of Abnormal Cytology Results Suggesting High-Grade Intraepithelial Lesions in Women over 50 Years of Age—Evaluation of the Clinical Utility of Conventional Gynecological Cytology

<b>Objectives</b>: Cervical cancer remains a major health concern worldwide. In women aged ≥ 50, diagnostic accuracy may be compromised due to menopausal changes such as atrophy and squamocolumnar junction displacement. Cytology remains the primary screening tool in many regions, including Poland, although its sensitivity and specificity are limited. This study assessed the concordance between cytological diagnoses of high-grade squamous intraepithelial lesions (HSILs); atypical squamous cells, which cannot exclude HSIL (ASC-H); atypical glandular cells (AGCs); and histopathological verification in women aged ≥ 50 years, highlighting the limitations of current diagnostic pathways. <b>Methods</b>: A retrospective analysis was conducted on women aged ≥ 50 years referred between 2018-2024 with abnormal cytology. All patients underwent colposcopic assessment followed by histopathological verification supported by p16 immunostaining. Cytological and histopathological results were compared. Associations between clinical variables and diagnostic concordance were tested using the chi-square test (α = 0.05). <b>Results</b>: Among 79 patients, histopathology confirmed high-grade squamous intraepithelial lesions with cervical intraepithelial neoplasia grade 2 or higher (HSIL/CIN2+) in 38%. Low-grade squamous intraepithelial lesions with cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) were found in 11%, and vaginal intraepithelial neoplasia grade 1 (VAIN1) in 4%, while 47% demonstrated inflammatory changes or no abnormalities. HSIL cytology showed the highest concordance, whereas AGC was more frequently associated with benign findings. No statistically significant association was detected between cytology accuracy and clinical characteristics (<i>p</i> > 0.05), highlighting the need for further studies in larger cohorts. <b>Conclusions</b>: In women aged ≥ 50, abnormal cytology frequently overestimated the severity of cervical pathology. Reliance on cytology alone may lead to overtreatment or misclassification, particularly in the presence of atrophic or inflammatory changes. Complementary use of human papillomavirus (HPV) genotyping and molecular markers alongside histopathological verification is recommended to enhance diagnostic precision in this population.