ORIGINAL ARTICLE
IMPLEMENTATION OF P16/KI67 DUAL STAINING CYTOLOGY FOR DETECTING CERVICAL DYSPLASIA

UDK: 618.146-006.6-076.5

Milkovski D1, Janevska V1, Stojovski M1, Jovanovska V1, Stanojevik V1, Kjaev I1

 

1University Clinic for Obstetrics and Gynecology, Faculty of Medicine, “Ss Cyril and Methodius” University in Skopje, North Macedonia

 

Abstract:

Cervical cancer is the fourth most common cancer among women worldwide. Vaccination against oncogenic human papillomaviruses (HPV) and effective screening have made cervical cancer preventable. Current screening methods, including cytology, HPV testing, and a combination of both, have limitations, highlighting the need for additional markers to identify high-grade cervical lesions (CIN2+).

p16/Ki67 dual immunocytochemistry staining is a biomarker with high sensitivity and specificity for detecting CIN2+ lesions. Incorporating this biomarker in triage, alongside cytology and HPV testing, can help avoid unnecessary referrals for colposcopy and biopsy.

This study, conducted at the University Clinic for Gynecology and Obstetrics in Skopje over a one-year period, involved 40 female patients aged 21 to 65 years, all of whom underwent HPV DNA testing, cytological testing (LB) and p16/Ki67 dual staining. The study found a significant association between High-Grade Squamous Intraepithelial Lesion (HSIL) and p16/Ki67 dual staining (p=0.012), while no significant association was observed between Low-Grade Squamous Intraepithelial Lesion (LSIL) and p16/Ki67 staining (p=1.0).

 

Key Words: cervical dysplasia; HPV; immunocytochemistry; p16/Ki67.

 

References:

 

  1. Singh D, Vignat J, Lorenzoni V, et al. Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. Lancet Glob Health. 2023 Feb;11(2):e197-e206. doi: 10.1016/S2214-109X(22)00501-0. Epub 2022 Dec 14. PMID: 36528031; PMCID: PMC9848409.
  2. Global strategy to accelerate the elimination of cervical cancer as a public health problem. Geneva: World Heatlh Organization; 2020 (https://www.who.int/publications/i/item/9789240014107).
  3. Ginsburg O Bray, F Coleman MP et al. The global burden of women’s cancers: a grand challenge in global health. Lancet. 2017; 389: 847-860.
  4. Cibula D, Raspollini MR, Planchamp F, et al. ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer – Update 2023. Int J Gynecol Cancer. 2023 May 1;33(5):649-666. doi: 10.1136/ijgc-2023-004429. PMID: 37127326; PMCID: PMC10176411.
  5. https://cdn.who.int/media/docs/default-source/country-profiles/cervical-cancer/cervical-cancer-mkd-2021-country-profile-en.pdf?sfvrsn=27b124a6_38&download=true
  6. WHO. Global strategy to accelerate the elimination of cervical cancer as a public health problem. Geneva: World Health Organization, 2020.7.https://www.cancer.gov/types/cervical/causes-risk-prevention.
  7. https://www.cancer.gov/types/cervical/causes-risk-prevention
  8. Castle, P.E.; Stoler, M.H.; Wright, T.C., Jr.; Sharma, A.; Wright, T.L.; Behrens, C.M. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: A subanalysis of the ATHENA study. Lancet Oncol. 2011, 12, 880–890.9.
  9. https://www.who.int/news-room/fact-sheets/detail/cervical-cancer.
  10. Pathak P, Pajai S, Kesharwani H. A Review on the Use of the HPV Vaccine in the Prevention of Cervical Cancer. Cureus. 2022 Sep 2;14(9):e28710. doi: 10.7759/cureus.28710. PMID: 36211088; PMCID:.
  11. Klaes R, Woerner SM, Ridder R, Wentzensen N, Duerst M, Schneider A. et al. Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integrated papillomavirus oncogenes. Cancer Res. 1999;59:6132–6.
  12. WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention, second edition (https://iris.who.int/bitstream/handle/10665/342365/9789240030824-eng.pdf?sequence=1)
  13. Yu L, Fei L, Liu X, Pi X, Wang L, Chen S. Application of p16/Ki-67 dual-staining cytology in cervical cancers. J Cancer 2019; 10(12):2654-2660. doi:10.7150/jca.32743. https://www.jcancer.org/v10p2654.htm.
  14. Kituncharoen S, Tantbirojn P, Niruthisard S. Comparison of Unsatisfactory Rates and Detection of Abnormal Cervical Cytology Between Conventional Papanicolaou Smear and Liquid-Based Cytology (Sure Path®). Asian Pac J Cancer Prev. 2015;16(18):8491-4. doi: 10.7314/apjcp.2015.16.18.8491. PMID: 26745107.
  15. Massad LS, Einstein MH, Huh WK, et al. 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013 Apr;121(4):829-846. doi: 10.1097/AOG.0b013e3182883a34. PMID: 23635684.
  16. Wright TC, Stoler MH, Behrens CM, Sharma A, Zhang G, Wright TL. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015 Feb;136(2):189-97. doi: 10.1016/j.ygyno.2014.11.076. Epub 2015 Jan 8. PMID: 25579108.
  17. Dovnik, A.; Repše Fokter, A. The Role of p16/Ki67 Dual Staining in Cervical Cancer Screening. Curr. Issues Mol. Biol. 2023, 45, 8476–8491. https://doi.org/10.3390/ cimb45100534.