Cervical Cytology-Histopathology Concordance and Role of Dual Immunomarkers in Biopsy Samples of Uterine Cervix: A Cross-sectional Study from a Tertiary Care Hospital of West Bengal, India

Abstract

Introduction: Cervical cancer is one of the leading causes of cancer deaths. Liquid-based cervical cytology enables the detection and diagnosis of the disease at an early stage. p40 is a specific immunomarker that distinguishes squamous cell carcinomas from other cervical carcinomas with glandular and neuroendocrine differentiation. Aim: To determine the role of Liquid-based Cytology (LBC) in the early detection of premalignant and malignant lesions of the uterine cervix and its concordance with histopathological findings. Materials and Methods: This cross-sectional study was conducted at the Institute of Post Graduate Medical Education and Research (IPGME&R), Kolkata, West Bengal, India, over a period of one year and six months (from October 2020 to March 2022). Cervical samples were collected from a total of 200 females, and the materials were processed using the BD SurePath™ LBC method. The cytologically confirmed cases were biopsied, and histopathological concordance was established. Immunohistochemical (IHC) staining for p40 and p63 was performed using the peroxidase-antiperoxidase method to differentiate between premalignant, malignant squamous, and glandular lesions of the uterine cervix. For quantitative analysis, all cells were counted in 10 random fields at 400x magnification, and p63 and p40 were expressed as a percentage of positive cells per the total number of counted cells. Cases were considered positive if 5% or more of the tumour cell nuclei showed brown nuclear staining. The mean percentage positivity of p63 and p40 nuclear staining of all the cases in each category was calculated for non neoplastic and precursor/neoplastic lesions of the cervix. Results: Among the 200 cases evaluated by LBC, 169 (84.5%) were non neoplastic, and the remaining 31 (15.5%) were precursor/neoplastic lesions. The vast majority (126 cases, 63%) were inflammatory smears, followed by 20 cases (10%) that were Negative for Intraepithelial Lesion or Malignancy (NILM). Total of 40 cases were followed-up with biopsy and histopathology, and concordance with the cytological diagnosis was evaluated. Among 40 cases, 23 were precursor/neoplastic on histopathology, and seven cases that were non neoplastic on Histopathological Examination (HPE) had been correctly diagnosed on LBC, giving a concordance rate of 75%. The overall sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of LBC were 92%, 46.6%, 74.1%, and 77.7%, respectively, considering histological diagnosis as the gold standard. Regarding IHC expression on histopathology, the mean positivity of p40 and p63 for non neoplastic lesions was 9.40% and 10.06%, and for precursor/neoplastic lesions, 47.44% and 46.4%, respectively. Adenocarcinoma-in-situ and adenocarcinoma were negative for both p40 and p63. Conclusion: Cervical cytology is a less invasive, cost-effective, and simple procedure to diagnose cervical epithelial cell abnormalities. Cytological-histopathological concordance revealed that LBC is a sensitive diagnostic method. The comparison between non neoplastic and neoplastic lesions of the cervix revealed a statistically significant difference with respect to the mean percent positivity of p40 and p63 IHC staining. Both of these markers can be used to differentiate squamous cell carcinoma from adenocarcinoma of the cervix.

Keywords

• immunohistochemistry
• liquid based cytology
• p40
• p63
• uterine cervical neoplasm