DOI QR코드

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Comparison Between Two Detection Methods for HPV16, HPV18 and P16Ink4a Biomarkers in Diagnosis of Abnormal Cervical Cytology

  • 발행 : 2016.12.01

초록

Background: Cervical cancer is the second most common cancer among women in many populations. While the Pap smear is a well established screening test it suffers from both false-positive and false-negative results in diagnosis of cancers and precancerous states. In this study, immunocytochemistry of the P16 biomarker and HPV-PCR were compared for their diagnostic potential. Materials and methods: In the study, we obtained pairs of specimens from 45 women with cervical dysplasia. One sample was placed in a liquid-based solution, and processed for staining of sections with antibodies to P16. HPV-PCR was performed on the other and the results obtained were analyzed by T-test using SPSS v. 15. Results: Using HPV-PCR 71% of the samples were found to be infected with either HPV 16 or HPV 18, and the rate of infection did not have a statistically significant relationship with higher grades of dysplasia (p= 0.253). In contrast, with immunocytochemistry evaluation of P16, 64% of the specimens were positive, but the percentage of positive results significantly increased with higher grades of dysplasia (p= 0.0001). Conclusion: Employment of the P16 marker as an optional test might be preferable over HPV-PCR for cervical dysplasia in our geographical region.

키워드

과제정보

연구 과제 주관 기관 : Kermanshah University of Medical Sciences

참고문헌

  1. Amortegui AJ, Meyer MP, Elborne VL, et al (1995). p53, retinoblastoma gene product, and cyclin protein expression in human papillomavirus virus DNA-positive cervical intraepithelial neoplasia and invasive cancer. Modern Pathol Inc, 8, 907-12.
  2. Aslani FS, Safaei A, Pourjabali M, et al (2013). Evaluation of Ki67, p16 and CK17 markers in differentiating cervical intraepithelial neoplasia and benign lesions. Iranian J Med Sci, 38, 15-21.
  3. Bibbo M, Klump WJ, DeCecco J, et al (2002). Procedure for immunocytochemical detection of P16INK4A antigen in thin-layer, liquid-based specimens. Acta Cytol, 46, 25-9. https://doi.org/10.1159/000326711
  4. Bruni L, Diaz M, Castellsague M, et al (2010). Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis, 202, 1789-99. https://doi.org/10.1086/657321
  5. Castle PE, Solomon D, Schiffman M, et al (2005). Human papillomavirus type 16 infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities. J Natl Cancer Inst, 97, 1066-71. https://doi.org/10.1093/jnci/dji186
  6. Cheah P-L, Koh C-C, Nazarina ar, et al (2016). Correlation of p16 (INK4a) immunoexpression and human papillomavirus (HPV) detected by in-situ hybridization in cervical squamous neoplasia. Malays J Pathol, 38, 33-8.
  7. Chen W, Zhang X, Molijn A, et al (2009). Human papillomavirus type-distribution in cervical cancer in China: the importance of HPV 16 and 18. Cancer Causes Control, 20, 1705-13. https://doi.org/10.1007/s10552-009-9422-z
  8. De Sanjose S, Diaz M, Castellsague X, et al (2007). Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis, 7, 453-9. https://doi.org/10.1016/S1473-3099(07)70158-5
  9. Dehn D, Torkko KC, Shroyer KR (2007). Human papillomavirus testing and molecular markers of cervical dysplasia and carcinoma. Cancer Cytopathol, 111, 1-14. https://doi.org/10.1002/cncr.22425
  10. Doorbar J (2006). Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci, 110, 525-41. https://doi.org/10.1042/CS20050369
  11. Duenas-Gonzalez A, Lizano M, Candelaria M, et al (2005). Epigenetics of cervical cancer. An overview and therapeutic perspectives. Mol Cancer, 4, 1. https://doi.org/10.1186/1476-4598-4-1
  12. Dyson N, Howley PM, Munger K, et al (1989). The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science, 243, 934-7. https://doi.org/10.1126/science.2537532
  13. Ellenson LH, Pirog EC, Kumar V, et al (2010). The female genital tract. robbins and cotran pathologic basis of disease, 8th ed. Elsevier.
  14. Gajanin R, Gajanin Z, Vujkovic Z, et al (2015). Immunohistochemical expression of p16INK4a in inflammatory, preneoplastic and neoplastic cervical lesions. Med Pregled, 68, 85-92. https://doi.org/10.2298/MPNS1504085G
  15. Hillemanns P, Wang X (2006). Integration of HPV-16 and HPV- 18 DNA in vulvar intraepithelial neoplasia. Gynecol Oncol, 100, 276-82. https://doi.org/10.1016/j.ygyno.2005.10.003
  16. Holladay EB, Logan S, Arnold J, et al (2006). A comparison of the clinical utility of p16INK4a immunolocalization with the presence of human papillomavirus by hybrid capture 2 for the detection of cervical dysplasia/neoplasia. Cancer Cytopathol, 108, 451-61. https://doi.org/10.1002/cncr.22284
  17. Johnson LD, Nickerson RJ, Easterday CL, et al (1968). Epidemiologic evidence for the spectrum of change from dysplasia through carcinoma in situ to invasive cancer. Cancer, 22, 901-14. https://doi.org/10.1002/1097-0142(196811)22:5<901::AID-CNCR2820220502>3.0.CO;2-J
  18. Konya J, Veress G, Hernadi Z, et al (1995). Correlation of human papillomavirus 16 and 18 with prognostic factors in invasive cervical neoplasias. J Med Virol, 46, 1-6. https://doi.org/10.1002/jmv.1890460102
  19. Lesnikova I, Lidang M, Hamilton-Dutoit S, et al (2009). p16 as a diagnostic marker of cervical neoplasia: a tissue microarray study of 796 archival specimens. Diagn Pathol, 4, 1746-596.
  20. Milde-Langosch K, Hagen M, Bamberger A-M, et al (2003). Expression and prognostic value of the cell-cycle regulatory proteins, Rb, p16MTS1, p21WAF1, p27KIP1, cyclin E, and cyclin D2, in ovarian cancer. Int J Gynecol Pathol, 22, 168-74. https://doi.org/10.1097/00004347-200304000-00009
  21. Monsonego J, Hudgens MG, Zerat L, et al (2011). Evaluation of oncogenic human papillomavirus RNA and DNA tests with liquid-based cytology in primary cervical cancer screening: The FASE study. Int J Cancer, 129, 691-701. https://doi.org/10.1002/ijc.25726
  22. Murphy N, Ring M, Heffron C, et al (2005). p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasia and cervical cancer. J Clinical pathol, 58, 525-34. https://doi.org/10.1136/jcp.2004.018895
  23. Murphy N, Ring M, Killalea A, et al (2003). p16INK4A as a marker for cervical dyskaryosis: CIN and cGIN in cervical biopsies and $ThinPrep^{TM}$ smears. J Clin Pathol, 56, 56-63. https://doi.org/10.1136/jcp.56.1.56
  24. Nieh S, Chen S-F, Chu T-Y, et al (2003). Expression of p16 INK4A in Papanicolaou smears containing atypical squamous cells of undetermined significance from the uterine cervix. Gynecol Oncol, 91, 201-8. https://doi.org/10.1016/S0090-8258(03)00479-7
  25. Piroozmand A, Zadeh SMM, Madani A, et al (2016). The association of high risk human papillomaviruses in patients with cervical cancer: An evidence based study on patients with squamous cell dysplasia or carcinoma for evaluation of 23 human papilloma virus genotypes. Jundishapur J Microbiol, 9.
  26. Rocco JW, Sidransky D (2001). p16 (MTS-1/CDKN2/INK4a) in cancer progression. Exp cell Res, 264, 42-55. https://doi.org/10.1006/excr.2000.5149
  27. Ryan KJ (1999). Kistner's gynecology and women's health, Mosby Incorporated.
  28. Sahebali S, Depuydt CE, Boulet GA, et al (2006). Immunocytochemistry in liquid-based cervical cytology: analysis of clinical use following a cross-sectional study. Int J Cancer, 118, 1254-60. https://doi.org/10.1002/ijc.21489
  29. Sano T, Oyama T, Kashiwabara K, et al (1998). Expression status of p16 protein is associated with human papillomavirus oncogenic potential in cervical and genital lesions. Ame J Pathol, 153, 1741-8. https://doi.org/10.1016/S0002-9440(10)65689-1
  30. Saqi A, Pasha TL, McGrath CM, et al (2002). Overexpression of p16INK4A in liquid-based specimens ($SurePath^{TM}$) as marker of cervical dysplasia and neoplasia. Diagn Cytopathol, 27, 365-70. https://doi.org/10.1002/dc.10205
  31. Sargent A, Bailey A, Almonte M, et al (2008). Prevalence of typespecific HPV infection by age and grade of cervical cytology: data from the ARTISTIC trial. Br J Cancer, 98, 1704-9. https://doi.org/10.1038/sj.bjc.6604324
  32. Smeets SJ, van der Plas M, Schaaij-Visser T, et al (2011). Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways. Int J Cancer, 128, 1596-605. https://doi.org/10.1002/ijc.25474
  33. Solomon D, Nayar R (2004). The Bethesda System for reporting cervical cytology: definitions, criteria, and explanatory notes, Springer Science & Business Media.
  34. Stoler MH (2004). The pathology of cervical neoplasia. In 'Cercival Cancer: From Etiology to Prevention', Eds Springer, pp 3-59.
  35. Volgareva G, Zavalishina L, Andreeva Y, et al (2004). Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells. BMC Cancer, 4, 1. https://doi.org/10.1186/1471-2407-4-1
  36. von Knebel Doeberitz M (2002). New markers for cervical dysplasia to visualise the genomic chaos created by aberrant oncogenic papillomavirus infections. Eur J Cancer, 38, 2229-42. https://doi.org/10.1016/S0959-8049(02)00462-8
  37. Xiong Y, Kuppuswamy D, Li Y, et al (1996). Alteration of cell cycle kinase complexes in human papillomavirus E6-and E7-expressing fibroblasts precedes neoplastic transformation. J Virol, 70, 999-1008.
  38. Yildiz IZ, Usubutun A, Firat P, et al (2007). Efficiency of immunohistochemical p16 expression and HPV typing in cervical squamous intraepithelial lesion grading and review of the p16 literature. Pathol Res Pract, 203, 445-9. https://doi.org/10.1016/j.prp.2007.03.010
  39. Zhou X-B, Guo M, Quan L-P, et al (2003). Detection of human papillomavirus in Chinese esophageal squamous cell carcinoma and its adjacent normal epithelium. World J Gastroenterol, 9, 1170-3. https://doi.org/10.3748/wjg.v9.i6.1170