The Comparison of Cytology and Biomarker (P53 and Bcl2) Analysis in Cervical Neoplasia: A Prospective Study

Document Type : Original Article

Authors

1 Department of Pathology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

2 Department of Hematology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

3 Department of Gynae-oncology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

4 Department of Community Medicine, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

Abstract

Background and aim: Cervical cancer is females' fourth most common cancer. A Pap smear is most commonly used for cervical cancer screening but has a low sensitivity. So, biomarkers can improve the diagnostic efficiency of screening programs. The aim of this study is to evaluate the sensitivity and specificity of cytology and biomarkers p53 and Bcl2 in detecting cervical neoplasia considering histopathological examination as the gold standard.
Material and methods: It was a prospective hospital-based observational study. All cervical biopsies and surgically resected specimens received in the Histopathology laboratory of patients between 30-65 years were included.
Results: One hundred and sixty patients who visited the Gynae-Oncology Outpatient department during the study period were enrolled. Out of these 10 cases were premalignant lesions and 97 cases of invasive carcinoma. Squamous cell carcinoma was the most common histological subtype of invasive cancer. Keratinizing Squamous cell carcinoma was the most common histological subtype of squamous cell carcinoma, and also Endocervical Adenocarcinoma was the most common histological subtype of Adenocarcinoma. Cytology had high specificity of 96.2% and low sensitivity of 59.8% in detecting cervical neoplasia. p53 staining on immunohistochemistry had a sensitivity of 77.6% and specificity of 90.6%. Bcl2 staining on IHC had the highest specificity of 100% and sensitivity of 48%.
Conclusions: Combined use of cytology and biomarkers analysis increases the chances of detecting cervical cancer at early stages than using any single screening test. It will help in reducing patient morbidity and mortality.

Keywords

Main Subjects


[1]  Khan MA, Tiwari D, Dongre A, Mustafa S, Das CR, Massey S, et al. Exploring the p53 connection of cervical cancer pathogenesis involving north-east Indian patients. PloS one. 2020;15(9):e0238500. https://doi.org/10.1371/journal.pone.0238500.
[2]  Grace VB, Shalini JV, Devaraj SN, Devaraj H. Co-overexpression of p53 and bcl-2 proteins in HPV-induced squamous cell carcinoma of the uterine cervix☆. Gynecologic oncology. 2003;91(1):51-8. https://doi.org/10.1016/S0090-8258(03)00439-6.
[3]  Jin XW, Zanotti K, Yen-Lieberman B. New cervical cancer screening strategy: combined Pap and HPV testing. Cleveland Clinic journal of medicine. 2005;72(2):141-8. https://doi.org/10.3949/ccjm.72.2.141.
[4]  Dimitrakakis C, Kymionis G, Diakomanolis E, Papaspyrou I, Rodolakis A, Arzimanoglou I, et al. The possible role of p53 and bcl-2 expression in cervical carcinomas and their premalignant lesions. Gynecologic oncology. 2000;77(1):129-36. https://doi.org/10.1006/gyno.1999.5715.
[5]  Kurita T. Developmental origin of vaginal epithelium. Differentiation. 2010;80(2-3):99-105. https://doi.org/10.1016/j.diff.2010.06.007.
[6]  Nayar R, Wilbur DC. The pap test and Bethesda 2014. Acta cytologica. 2015;59(2):121-32. https://doi.org/10.1159/000381842.
[7]  Dahiya N, Bachani D, Acharya AS, Sharma DN, Gupta S, Haresh KP. Socio-demographic, reproductive and clinical profile of women diagnosed with advanced cervical cancer in a tertiary care institute of Delhi. The Journal of Obstetrics and Gynecology of India. 2017;67(1):53-60. https://doi.org/10.1007/s13224-016-0907-x.
[8]  Jain A, Ganesh B, Bobdey SC, Sathwara JA, Saoba S. Sociodemographic and clinical profile of cervical cancer patients visiting in a tertiary care hospital in India. Indian Journal of Medical and Paediatric Oncology. 2017;38(03):291-5. https://doi.org/10.4103/ijmpo.ijmpo_20_16.
[9]  Deffar K, Abdelhalim K, Xie X, Ying L, Ouhida S, Mahnane A. Immunohistochemical expression of p53 and Bcl-2 in Algerian cervical carcinoma. Biomedical and Pharmacology Journal. 2018;11(1):67-75. https://dx.doi.org/10.13005/bpj/1348.
[10] Kumari A, Pankaj S, Choudhary V, Kumari A, Nazneen S, Kumari J, et al. Retrospective analysis of patients of cervical cancer a tertiary center in Bihar. Indian Journal of Cancer. 2018;55(1):70-3. https://doi.org/ 10.4103/ijc.IJC_482_17.
[11] Rana MK, Singh K, Mahajan MK, Rana AP. Clinicopathological profile of cervical carcinoma: an experience of tertiary care cancer centre. Asian Pacific Journal of Cancer Care. 2019;4(3):83-6. https://doi.org/10.31557/APJCC.2019.4.3.83-86.
[12] Jain R, Nigam RK, Malik R, Jain P. Clinicopathological presentation of cervical cancer in Bhopal. Indian Journal of Medical and Paediatric Oncology. 2019;40(S 01):S33-7. https://doi.org/10.4103/ijmpo.ijmpo_185_17.
[13] Jain A, Jain R, Iqbal KG, Dhannanjay S, Tusar K. Histopathological study of tumours of cervix. Advances in Cancer Research and Therapy. 2014;1:1-8.
[14] Rani R, Kumar R, Trivedi V, Singh U, Chauhan R, Ali M, et al. Age, parity and stages of cervix cancer: a hospital based study. Br J Med Health Res. 2016;3(4):73-82.
[15] Nanda A, Bansal N, Gupta V, Sharma A, Tandon A, Singhal M. Correlation between Cytology, HPV-DNA test and colposcopy in evaluation of cervical intraepithelial lesions. Journal of SAFOMS. 2014;2(2):71-4. https://doi.org/10.5005/jp-journals-10032-1045.
[16] RaghavendraAbhishitha G, Himabindu P, Devi SU. Cervical Cancer Screening By Cytology, Colposcopy and Their Correlation with Histopathology. 2019;18(12):21-5. https://doi.org/10.9790/0853-1812092125.
[17] Adamopoulou M, Kalkani E, Charvalos E, Avgoustidis D, Haidopoulos D, Yapijakis C. Comparison of cytology, colposcopy, HPV typing and biomarker analysis in cervical neoplasia. Anticancer Research. 2009;29(8):3401-9.
[18] Bobdey S, Sathwara J, Jain A, Balasubramaniam G. Burden of cervical cancer and role of screening in India. Indian journal of medical and paediatric oncology. 2016;37(04):278-85. https://doi.org/10.4103/0971-5851.195751.
[19] Baskaran K, Karunanithi S, Sivakamasundari I, Sundresh NJ, Thamaraiselvi B, Swaruparani S. Overexpression of p53 and its role as early biomarker in carcinoma od uterine cervix. Int J Res Pharm Sci 2013; 4(2):198-202.
[20] Sandhu JK, Shivakumar S. Study of p53 in cervical intraepithelial neoplasia and carcinoma cervix with clinico-pathological correlation. Int J Sci Stud. 2016;4(1):208-14.
[21] Shukla S, Dass J, Pujani M. p53 and bcl2 expression in malignant and premalignant lesions of uterine cervix and their correlation with human papilloma virus 16 and 18. South Asian Journal of Cancer. 2014;3(01):048-53. https://doi.org/10.4103/2278-330X.126524.
[22] Barpande CP, Gaopande VL, Joshi AR. Immunohistochemical study of invasive squamous cell carcinoma of uterine cervix and cervical intraepithelial neoplasia using Bcl-2, p53 and Ki-67. Journal of Evidence Based Medicine and Healthcare. 2018;5(52):3584-8. https://doi.org/10.18410/jebmh/2018/730.
[23] Kamaraddi S, Nayak A, Honnappa S, Swarup A. Expression of Bcl-2 marker in premalignant lesions of cervical cancer. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2016;5(4):965-70.