P16/Ki-67 Dual Staining Improve Detection of High-Grade Intraepithelial Lesions and Cervical Cancer.
DOI:
https://doi.org/10.61841/pej3ns22Keywords:
p16/ki-67 dual immunostaining, ASC-US, LSIL, LBC, colposcopy guided biopsy .Abstract
Abstract--Worldwide, cervical intraepithelial lesions are common in adult women , after the age of 30 years . The high grade lesions are precancerous and could transformed to in situ and invasive squamous cell carcinoma of uterian cervix .These transformation significantly can be reduced by screening program of the cervix ,namely : cytology, HR-HPV test , and colposcopy .
Women with cytology of utrian cervix that showed morphology of intraepithelial lesions ,especially high grade lesions , HR-HPV test should be done for these women . However , high prevalence of HPV infection can`t predicate the risk of malignant transformation in these women , thus additional triage test , including biomarkers for transformed cells can be used to detect women need further evaluation , follow up and treatment .
In current study , p16/Ki-67 dual immunostaining , was used for cytology as biomarker for detection of cellular changes and can improve the diagnosis of precancerous lesions and cervical squamous cells carcinoma .
Aim of the study: To identify the role of p16/ki-67 dual immunostaining in predicting the presence of significant cervical lesions in women with mild cytological atypia .
Patients , material and method: A prospective study of 317 women , with average age 39 years , over a period of December 2017 to August 2019, in Bagdad city and Salahaden Government .Patients were referred from private gynecological clinics to private lab of Dr.Salim Rasheed Al-Obaidi in Baghgad city and Lab of Dr. Inas Abd Al Majed Rasheed in Salahaden Government. All cytological smears from these women that were showed cytological morphology of intraepithelial lesions , were tested for HR-HPV ( by PCR ) , and p16/ki-67 dual immunostaining of cytology followed by colposcopy-guided biopsy were done for 58 women .
Results: Positively staining cells for p16/Ki-67 dual staining showed dark red –red brown nuclei , with clear or brownish cytoplasm . Positive slides are defined by presences of one or more cervical epithelial cells that expressed simultaneously stained for both p16/Ki-67 markers.
It has been shown the sensitivity and specificity of immunostaining in diagnosis of CIN2/CIN3 for ASC-US and LSIL lesions were (100 and 73%), and (100-89.7%) respectively.p16/ki-67 immunostaining positivity also increased with cytological severity in corresponded to histological morphology.
Conclusion: In addition to cytological evaluation and HR-HPV testing in women with cervical intraepithelial lesions , p16/ki-67 dual immunostaining of useful value in triage of ASC-US and LSIL lesions , according to high sensitivity and specificity .
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1. Mello V , Sundstrom RK . Cancer , Cervical Intraepithelial Neoplasia (CIN).(Update2019 June 16). In: StatPearls.
2. Sredevi A, Javed R , Dinesh A . Epidemiology of cervical cancer with special focus on India . Int J women Health .2015, 7: 405-14.
3. Possati-Resende JC , Fregnani JHTC, Kerr LM , Mauad EC , Longatto-Filho A, Scapulatempo-Neto C. The accuracy of p16/Ki-67 and HPV test in the detection OF cin2/3 in women diagnosed with ASC-US or LSIL .PLoS One .2015 , 10
4. O.Veijalainen,S. Tuomisaari , T. Luukkaala, and J. Laenpaa . "High risk HPV testing in the triage of repeat ASC-US and LSIL " .Acta Obstetricia et Gynecologica Scandinavica , 2015. vol. 94, no.9 , pp.931-936.
5. X.He, H. C. Tao , S. Z. Wang et al ."An analysis of high risk human papillomavirus DNA- negative cervical intraepithelial neoplasia in atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions smears : a retrospective study ". Journal of Capital Medical University , 2015 , vol.36 , no.2, pp.205-211, View at :google scholar .
6. Bongani G , Taverna F, Lombardo C, Borghi C, Martinelli F , Signorelli M , et al .Retrospective study of the influence of HPV persistence on outcomes among women with high -risk HPV infection and negative cytololgy .Int J Gynecol Obstet. 2017, 138: 62-8
7. Diya Das , Moumita Sengupta , Keya Basu , Mona Tirky , Chhanda Datta , and Uttara Chatterjee.Role of p16/Ki-67 Dual Immunostaining in Detection of Cervical Cancer Precursors. J Cytol .2018 Jul-Sep
,35(3): 153-158.
8. Li Yu , Lingyan Fei , Xubin Liu , Xufang Pi , Liantang Wang , and Shangwu Chen .Application of p16/Ki-67 dual-staining cytology in cervical cancer.
9. Vikrant Bhar Singh , Nalini Gupta , Raje Nijhawan , Radhika Srinivasan , Vanita Suri , Arvind Rajwanshi .Liquid –based cytology versus conventional cytology for evaluation of cervical Pap smears
:Experience from the first 1000 split samples .Indian Journal of Pathology &Microbiology.2015 , 58(1): 17-21.
10. Denton KJ .Liquid based cytology in cervical cancer screening .BMJ. 2007;335(7609):1-2.
11. Veronika Kloboves Prevodnik , Tine Jerman , et al . Interobserver variability and accuracy of p16/Ki-67 dual immunocytochemical staining on conventional cervical smear .Diagnostic Pathology .2019, 14: 48
12. Kisser A, Zechmeister-Koss I .A systemic review of p16/Ki-67 immunostaining for triage of low grade cervical cytology .BJOG .2015 ; 122:64-70
13. Waldstrom M , Christensen RK, Ornskov D. Evaluation of p16/Ki-67 dual staining in comparison with an mRNA human papillomavirus test on liguid –based cytology samples with low –grade squamous intraepithelial lesion .Cancer Cytopathol.2013; 121: 136-45.
14. Stoler MH , Schiffman M. Interobserver reproducibility of cervical cytology and histologic interpretations: Realistic estimates from the ASCUS-LSIL triage study .JAMA. 2001; 285:1500-5.
15. Stoler MH, Wright TC, Sharma A, Apple R ,Gutekunst K , Wright TL . High –risk human papillomavirus testing in women with ASC-US cytology results from ATHENA HPV study .Am J Clin Pathol.2011, 135:468-75.
16. Edgerton N, Cohen C, Siddiqui MT . Evaluation of CINtec PLUS® testing as an adjunctive test in ASC-US diagnosed SurePath® preparation .Diagn Cytopathol.2013 ; 41:35-40.
17. Walker JL, Wang SS, Schiffman M , Solomon D. Predicting absolute risk of CIN3 during post-colposcopic follow –up : Results from the ASCUS-LISL Triage study (ALTS).Am J Obstet Gynecol. 2006; 195:341-8.
18. Cuzick j , Arbyn M , Sankaranarayanan R, Tus V, Ronco g , Mayrand M-H, et al .Overview of human papillomavirus –based and other novel options for cervical cancer screening in developed and developing countries .Vaccine .2008;26:6743-4.
19. Wentzensen N , Schwartz L, Zuna RE , Smith K , Mathews C, Gold MA ,et al .Performance of p16/Ki-67 immunostaining to detect cervical cancer precursors in colposcopy referral population .Clin Cancer Res. 2012 ;18: 4154-62.
20. Petry KU, Schmidt D, Scherbring S, Luyten A, Reinecke –Luthge A, Bergeron C, et al.Triaging Pap cytology negative , HPV positive cervical cancer screening results with p16/Ki-67 dual –stained cytology. Gynecol Oncol. 2011; 121:505-9.
21. Schmidt D, Bergeron C, Denton KJ , Ridder R. p16/Ki-67 dual –stain cytology in triage of ASCUS and LSIL Papanicolaou cytology : results from theEuropean equivocal or mildly abnormal Papanicolaou cytology study .Cancer Cytopathol. 2011;119: 158-66.
22. Loghavi S, Walts AE , Bose S. CINtec® PLUS dual immunostain : a triage tool for cervical pap smears with atypical squamous cells of undertermined significance and low grade squamous intraepithelial lesion .Diagn Cytopathol. 2013;41:582-7.
23. Dona MG , Vocaturo A, Giuliani M , Ronchetti L, Rollo F , Pescarmona E, et al .p16/Ki-67 dual staining in cervico-vaginal cytology: correlation with histology , Human Papillomavirus detection and genotyping in women undergoing colposcopy .Gynecol Oncol.2012; 126: 198-202.
24. Yasar, Mustafa, and . 2019. The remember regeneration therapy method: An overview of new therapy protocol to approach diseases. Journal of Complementary Medicine Research, 10 (1), 68-
80. doi:10.5455/jcmr.20181229122909
25. Adediran, O., Akintunde, A.A., Edo, A.E., Opadijo, O.G., Araoye, A.Impact of urbanization and gender on frequency of metabolic syndrome among native Abuja settlers in Nigeria(2012) Journal of Cardiovascular Disease Research, 3 (3), pp. 191-196. DOI: 10.4103/0975-3583.98890
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