The detection of human papilloma virus 16 L1 capsid protein and p16 in cervical lesions

  • Jugder Uranbolor
  • Dongobat Erdenetsogt
  • Lodon Galtsog
  • Jav Sarantuya

Abstract

Background

Cervical cancer is the second most common type of cancer in women worldwide and also the second most common female malignancy in Mongolia. The association of p16 and hr-HPV in Asia and in more particular in Mongolia are still relatively unexplored. So we aimed to detect the immunohistochemistry expression of p16 and L1 protein of HPV16 and to investigate the combined expression of these markers in cervical lesions.

Methods

A total of 96 cases were selected from the records of Pathology services, National Cancer center of Mongolia. There were 50 cases diagnosed as LSIL and 46 cases diagnosed as HSIL. The immunohistochemical staining with p16 and HPV 16 L1 were done on all cases.

Results

The positive rate of HPV 16 L1 capsid protein was identified 74% in LSIL cases and 52% in HSIL cases.There were a significant difference for HPV16 in HSIL and LSIL groups.Immunohistochemistry of p16 staining shows 76% in  LSIL cases and 72% in HSIL cases. There was not a statistically significant difference for p16 in HSIL and LSIL groups. A chi square test was used to analyze the result and the obtained p value was <0.05.

Conclusion

The combination between hr-HPV and p16 is considered to be more useful, having a higher accuracy than hr-HPV or p16 alone. There is still critical need, to find other molecular surrogate markers, which can provide accurate information about which precursor lesions would progress toward cancer. 

Downloads

Download data is not yet available.

Author Biographies

Jugder Uranbolor
Gynecology and Obstetrics Department, MNUMS
Dongobat Erdenetsogt
Pathology Department, MNUMS

References

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin.2011;61:69–90.

2. Koss L. The Papanicolaou test for cervical cancer detection: a triumph and a tragedy. JAMA.1989; 261:737–743.

3. Papanicolaou GN. Science. 1942;95:438–439.

4. Ostor AG. Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol. 1993;12:186–192.

5. Stoler MH, Schiffmann M. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA. 2001;285:1500–1505.

6. Follen M. Richard –Kortum R. Emerging technologies and cervical cancer. J Natl Cancer Inst.2000;92:363–365.

7. Group ALTS. Human papillomavirus testing for triage of women with cytological evidence of low grade squamous intraepithelial lesions triage study (ALTS) Group. J Natl Cancer Inst. 2000;105:397–402
.
8. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12–19.

9. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Eng J Med. 1998;338:423–428.

10. Bergeron C, Wentzensen N, Cas F, von Knebel Doeberitz M. La proteine p16INK4a: un marquercytologique pour detecter les neoplasies intraepitheliales de haut grade du col uterin. Ann Pathol 2006;26:397–402.

11. Carozzi FM, Cecchini S, Confortini M, Becattini V, Cariaggi MP, Pontenani G, et al. Role of p16 INK4a expression in identifying CIN2 or more severe lesions among HPV-positive patients referred for colposcopy after abnormal cytology. Cancer 2006;108:119–23.

12. Bibbo M, Klump WJ, DeCecco J, Kovatich A. Procedure for immunocytochemical detection of p16 INK4a antigen in Thin-Layer, liquid-based specimens. Acta Cytol 2002;46:25–9.

13. Benvolo M, Mottolese M, Marandino F, Vocaturo G, Sindico R, Piperno G, Mariani L, Sperduti I, Canalini P, Donnorso RP, Vocaturo A. Immunohistochemical expression of p16INK4A is predictice of HR-HPV infection in cervical low grade lesions. Mod Pathol. 2006;19:384–391.

14. Battogtokh Ch, Chin Y P, Avirmed D,Okamoto N, Yohei M, Distribution of HPV 16 intratypic variants among women with cervical intraepithelial neoplasia and invasive cervical cancer in Mongolia.Asian pac.2008;1-6

15. Münger K, Baldwin A, Edwards KM, Hayakawa H,Nguyen CL, Owens M, et al. Mechanisms of human papillomavirus-induced oncogenesis. J Virol 2004;78:1145l-11460.

16. Rao PH, Arias-Pulido H, Lu XY, Harris CP, VargasH, Zhang FF, et al. Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequentgenetic changes in cervical carcinoma. BMC Cancer2004; 4:5.

17. Wilting SM, de Wilde J, Meijer CJ, Berkhof J, Yi Y,van Wieringen WN, et al. Integrated genomic andtranscriptional profiling dentifies chromosomal lociwith altered gene expression in cervical cancer.Genes Chromosomes Cancer 2008; 47:890-905.

18. Sugita M, Tanaka N, Davidson S, Sekiya S, Varella Garcia M, West J,et al. Molecular definition of a small amplification domain within 3q26 in tumors ofcervix, ovary, and lung. Cancer Genet Cytogenet 2000;l17:9-18.
19. Lee H, Lee KJ, Jung CK, et al. Expression of HPV L1 capsid protein in cervical specimens with HPV infection. Diagn Cytopathol. 2008; 36:864–867. [PubMed: 18855883]

20. Melsheimer P, Kaul S, Dobeck S, Bastert G. Immunocytochemical detection of HPV high-risk type L1 capsid proteins in LSIL and HSIL as compared with detection of HPV L1 DNA. Acta Cytol.2003; 47:124–128. [PubMed: 12685176]

21. Griesser H, Sander H, Hilfrich R, Moser B, Schenck U. Correlation of immunochemical detection of HPV L1 capsid protein in pap smears with regression of high-risk HPV positive mild/moderate dysplasia. Anal Quant Cytol Histol. 2004; 26:241–245. [PubMed: 15560527]

22. Lee H, Lee KJ, Jung CK, et al. Expression of HPV L1 capsid protein in cervical specimens with HPV infection. Diagn Cytopathol. 2008; 36:864–867. [PubMed: 18855883]

23. Melsheimer P, Kaul S, Dobeck S, Bastert G. Immunocytochemical detection of HPV high-risk type L1 capsid proteins in LSIL and HSIL as compared with detection of HPV L1 DNA. Acta Cytol.2003; 47:124–128. [PubMed: 12685176]

24. Griesser H, Sander H, Hilfrich R, Moser B, Schenck U. Correlation of immunochemical detection of HPV L1 capsid protein in pap smears with regression of high-risk HPV positive mild/moderate dysplsia. Anal Quant Cytol Histol. 2004; 26:241–245. [PubMed: 15560527]

25. Griesser H, Sander H, Walczak C, Hilfrich RA. HPV vaccine protein L1 predicts disease outcome of high-risk HPV+ early squamous dysplastic lesions. Am J Clin Pathol. 2009; 132:840–845.[PubMed: 19926574]

26. Xiao W, Bian M, Ma L, et al. Immunochemical analysis of human papillomavirus L1 capsid protein in liquid-based cytology samples from cervical lesions. Acta Cytol. 2010; 54:661–667. [PubMed: 20968152]

27. Yu L, Wang L, Zhong J, Chen S. Diagnostic value of p16INK4A, Ki-67, and human papillomavirus L1 capsid protein immunochemical staining on cell blocks from residual liquidbased gynecologic cytology specimens. Cancer Cytopathol. 2010; 118:47–55. [PubMed:20069634]

28. Rauber D, Mehlhorn G, Fasching PA, Beckmann MW, Ackermann S. Prognostic significance of the detection of human papilloma virus L1 protein in smears of mild to moderate cervical intraepithelial lesions. Eur J Obstet Gynecol Reprod Biol. 2008; 140:258–262. [PubMed:18621464]

29. Tsoumpou I, Arbyn M, Paraskevaidis E, Kyrgiou M, Wentzensen N, Koliopoulos G, Martin-Hirsch P. p16 INK4a immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis Cancer Treat Rev. 2009 May ; 35(3): 210–220.

30. Khleif SN, DeGregori J, Yee CL, Otterson GA, Kaye FJ, Nevins JR, Howley PM. Inhibition of cyclin D-CDK4/CDK 6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc Natl Acad Sci U S A. 1996;93:424–429.

31. Negri G, Vittadello F, Romano F, Kasal A, Rivasi F, Girlando S, et al. p16INK4a expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri. Virchows Arch 2004;445:616–20.

32. Wang SS, Trunk M, Schiffman M, Herreo R, Sherman M, Burk R, et al. Validation of p16 as a marker of oncogenic human papillomavirus infection in cervical biopsies form a population-based cohort in Costa Rica. Cancer Epidemiology Biomarkers Prev2004;23:1355–60.

33. Hariri J, Oster A. The negative predictive value of p16INK4a to assess the outcome of cervicalintraepithelial neoplasia 1 in the uterine cervix. Int J Gynecol Pathol 2007;26:223–8.

34. Yoshida T, Sano T, Kanuma T, et al. Usefulness of CINtec PLUS p16/Ki-67 double-staining in cytological screening of cervical cancer.Acta Cytol. 2011;55:413-20.
Published
2015-09-05
How to Cite
URANBOLOR, Jugder et al. The detection of human papilloma virus 16 L1 capsid protein and p16 in cervical lesions. Diagnostic Pathology, [S.l.], sep. 2015. ISSN 2364-4893. Available at: <https://www.diagnosticpathology.eu/content/index.php/dpath/article/view/66>. Date accessed: 29 mar. 2024. doi: https://doi.org/10.17629/www.diagnosticpathology.eu-2015-1:66.
Issue
Section
Research

Keywords

Immunohistochemistry; Human papillomavirus; Cervical cancer; p16