Role of p16 expression in preneoplastic and neoplastic lesions of cervix

Authors

  • Anurita Saigal Department of Pathology, IGMC Shimla, Himachal Pradesh, India
  • Anchana Gulati Department of Pathology, IGMC Shimla, Himachal Pradesh, India
  • Rajni Kaushik MMMU and Hospital, Kumarhatti, Solan, Himachal Pradesh, India
  • Digvijay Singh Dattal Department of Pathology, IGMC Shimla, Himachal Pradesh, India

DOI:

https://doi.org/10.18203/2320-6012.ijrms20241537

Keywords:

Cervical cancer, p16, HPV, Preneoplastic, Neoplastic

Abstract

Background: Cancer of the cervix is the leading cause of cancer among women in India. Human papilloma virus plays an important role in the causation of preneoplastic and neoplastic cervical lesions. HPV type-specific oncoproteins interact with cellular regulatory proteins resulting in upregulation of p16, a cyclin dependent kinase inhibitor. This has made p16, a valuable surrogate biomarker of HPV infection, useful in evaluating HPV associated preneoplastic and neoplastic lesions of cervix. The aim of this study was to evaluate p16 expression in preneoplastic and neoplastic cervical lesions.

Methods: A total of 93 specimens diagnosed histopathologically as cervical preneoplasia and neoplasia were included in this prospective study of one year duration. Maximum cases were of Neoplastic lesions followed by preneoplastic lesions. Majority of the neoplastic lesions were Squamous cell carcinoma. Immunohistochemical (IHC) staining for p16 was performed and was scored by percentage positivity and reaction intensity. p16 positivity in neoplastic lesions was significantly (p<0.0001) higher than preneoplastic lesions.

Results: Of the 93 cases, 17 (18.28%) were preneoplastic and 76 (81.72%) neoplastic lesions. In the preneoplastic group, 52.94% cases were p16 positive while 47. 06% cases revealed p16 negativity. Among the neoplastic group, 85.53% cases were p16 positive while 14.47% cases were p16 negative.

Conclusions: p16 expression progressively increased with increasing grades of cervical preneoplastic and neoplastic lesions, establishing p16 as a supplementary marker for early diagnosis of cervical cancer.

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References

WHO Information Centre on HPV and Cervical Cancer. Available at: https://www.who.int. Accessed on 20 November 2023,

Mzibri M, Attaleb M, Hassani A, Khyatti M, Benbacer L, Ennaji M, et al. Evaluation of p53, p16INK4a and E-Cadherin status as biomarkers for cervical cancer diagnosis, topics on cervical cancer with an advocacy for prevention. Pac J Cancer Prev. 2012;13(2):196-208.

Kumar V, Sagunthala P, Ravi S, Premalatha S. Analysis of Immuno histochemical Expression of P16INK4 a in preneoplastic squamous cell lesions of cervix. JDMS. .2016;15(3):46-51.

Gupta A, Ahmad MK, Mahndi AA, Singh R, Pradeep Y. Promoter Methylation and Relative mRNA Expression of the p16 Gene in Cervical Cancer in North Indians. Asian Pac J Cancer Prev. 2016;17(8):4149-54.

Agoff SN, Lin P, Morihara J, Mao C, Kiviat NB, Koutsky LA. p16 (INK4a) expression correlates with degree of cervical neoplasia: a comparison with Ki-67 expression and detection of high-risk HPV types. Mod Pathol. 2003;16:665-73.

Witkiewicz A, Wright T, Ferenczy A. Blaustein's pathology of the female genital tract. 6th ed. New York: Springer Verlag; 2011:6;254-64.

Redman R, Rufforny I, Liu C, Wilkinson EJ, Massoll NA. The utility of p16INK4a in discriminating between cervical intraepithelial neoplasia 1 and nonneoplastic equivocal lesions of the cervix. Arch Pathol Lab Med. 2008;132(5):795-9.

Tan GC, Norlatiffah S, Sharifah NA, Razmin G, Shiran MS, Hatta AZ, et al. Immunohistochemical study of p16 INK4A and survivin expressions in cervical squamous neoplasm. Indian J Pathol Microbiol. 2010;53(1):1-6.

Volgareva G, Zavalishina L, Andreeva Y, Frank G, Krutikova E, Golovina D, et al. Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells. BMC Cancer. 2004;4:58.

Kang S, Kim J, Kim HB, Shim JW, Nam E, Kim SH, et al. Methylation of p16 -INK4a is a non-rare event in cervical intraepithelial neoplasia. Diagn Mol Pathol. 2006;15:74-82.

Ferreux E. Evidence for at least three alternative mechanisms targeting the p16INK4A/cyclin D/Rb pathway in penile carcinoma, one of which is mediated by high-risk human papillomavirus. J Pathol. 2003;201:109-18.

Tripathi A, Banerjee S, Roy A, Roychowdhury S, Panda CK. Alterations of the P16 gene in uterine cervical carcinoma from Indian patients. Int J Gynecol Cancer. 2003;13:472-9.

Murphy N, Heffron CC, King B. p16INK4A positivity in benign, premalignant and malignant cervical glandular lesions: a potential diagnostic problem. Virchows Arch. 2004;445(6):610-5.

Izadi-Mood N, Asadi K, Shojaei H, Sarmadi S, Ahmadi SA, Sani S, et al. Potential diagnostic value of P16 expression in premalignant and malignant cervical lesions. J Res Med Sci. 2012;17(5):428.

Kishore V, Patil AG. Expression of p16INK4A Protein in Cervical Intraepithelial Neoplasia and Invasive Carcinoma of Uterine Cervix. J Clin Diagnos Res. 2017;11(9):EC17.

Umar A, Avwioro OG, Muhammad AT, Mohammed I, Mohammed MO, Ibrahim KK, et al. Immunohistochemical expression of p16 (ink4a) protein in cervical dysplasia and carcinoma in patients attending Federal Teaching Hospital, Gombe, Nigeria. Brunei Int Med J. 2016;12(7):41-6.

Lesnikova I, Lidang M, Hamilton-Dutoit S, Koch J. p16 as a diagnostic marker of cervical neoplasia: a tissue microarray study of 796 archival specimens. Diagn Pathol. 2009;4:22.

Srivastava S. P16INK4A and MIB-1: An immunohistochemical expression in preneoplasia and neoplasia of the cervix. Indian J Pathol Microbiol. 2010;53(3):518.

Kumari K, Vadivelan AA. P16INK4A expression in cervical intraepithelial neoplasia and cervical cancer. Brunei Int Med J. 2013;9(3):165-71.

Pao CC, Lin CY, Chang YL, Tseng CJ, Hsueh S. Human papillomaviruses and small cell carcinoma of the uterine cervix. Gynecol Oncol. 1991;43(3): 206-10.

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Published

2024-05-31

How to Cite

Saigal, A., Gulati, A., Kaushik, R., & Dattal, D. S. (2024). Role of p16 expression in preneoplastic and neoplastic lesions of cervix. International Journal of Research in Medical Sciences, 12(6), 1936–1940. https://doi.org/10.18203/2320-6012.ijrms20241537

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Original Research Articles