Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Significance of Human Telomerase RNA Gene Amplification Detection for Cervical Cancer Screening

  • Chen, Shao-Min (Department of Obstetrics and Gynecology, Weifang People's Hospital) ;
  • Lin, Wei (Department of Obstetrics and Gynecology, the Affiliated Hospital of Medical College, Qingdao University) ;
  • Liu, Xin (Department of Obstetrics and Gynecology, Weifang People's Hospital) ;
  • Zhang, You-Zhong (Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University)
  • Published : 2012.05.30
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Abstract

Aim: Liquid-based cytology is the most often used method for cervical cancer screening, but it is relatively insensitive and frequently gives equivocal results. Used as a complementary procedure, the high-risk human papillomavirus (HPV) DNA test is highly sensitive but not very specific. The human telomerase RNA gene (TERC) is the most often amplified oncogene that is observed in cervical precancerous lesions. We assessed genomic amplification of TERC in liquid-based cytological specimens to explore the optimal strategy of using this for cervical cancer screening. Methods: Six hundred and seventy-one residual cytological specimens were obtained from outpatients aged 25 to 64 years. The specimens were evaluated by the Digene Hybrid Capture 2 (HC2) HPV DNA test and fluorescence in situ hybridization (FISH) with a chromosome probe to TERC (3q26). Colposcopic examination and histological evaluation were performed where indicated. Results: The TERC positive rate was higher in the CIN2+ (CIN2, CIN3 and SCC) group than in the normal and CIN 1 groups (90.0% vs. 10.4%, p < 0.01). In comparison with the HC2 HPV DNA test, the TERC amplification test had lower sensitivity but higher specificity (90.0% vs. 100.0%, 89.6% vs. 44.0%, respectively). TERC amplification test used in conjunction with the HC2 HPV DNA test showed a combination of 90.0% sensitivity and 92.2% specificity. Conclusion: The TERC amplification test can be used to diagnose cervical precancerous lesions. TERC and HPV DNA co-testing shows an optimal combination of sensitivity and specificity for cervical cancer screening.

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References

  1. Apgar BS, Kittendorf AL, Bettcher CM, et al (2009). Update on ASCCP consensus guidelines for abnormal cervical screening tests and cervical histology. Am Fam Physician, 80, 147-55.
  2. Arbyn M, Buntinx F, Van Ranst M, et al (2004). Virologic Versus Cytologic Triage of Women With Equivocal Pap Smears: A Meta-analysis of the Accuracy To Detect High-Grade Intraepithelial Neoplasia. JNCI J Natl Cancer Inst, 96, 280-93. https://doi.org/10.1093/jnci/djh037
  3. Castle PE, Fetterman B, Poitras N, et al (2011). Variable risk of cervical precancer and cancer after a human papillomaviruspositive test. Obstet Gynecol, 117, 650-6. https://doi.org/10.1097/AOG.0b013e318209da59
  4. Castle PE, Wacholder S, Sherman ME, et al (2002). Absolute risk of a subsequent abnormal pap among oncogenic human papillomavirus DNA-positive, cytologically negative women. Cancer, 95, 2145-51. https://doi.org/10.1002/cncr.10927
  5. Cheah PL, Looi LM, Teoh KH, et al (2012). p16INK4a is a useful marker of human papillomavirus integration allowing risk stratification for cervical malignancies. Asian Pac J Cancer Prev, 13, 469-72. https://doi.org/10.7314/APJCP.2012.13.2.469
  6. Chen S, Yang Z, Zhang Y, et al (2012). Genomic amplification patterns of human telomerase RNA gene and C-MYC in liquid-based cytological specimens used for the detection of high-grade cervical intraepithelial neoplasia. Diagn Pathol, 7, 40. https://doi.org/10.1186/1746-1596-7-40
  7. Cox JT, Schiffman M, Solomon D, et al (2003). Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy. Am J Obstet Gynecol, 188, 1406-12. https://doi.org/10.1067/mob.2003.461
  8. Ekalaksananan T, Pientong C, Kongyingyoes B, et al (2011). Combined p16INK4a and human papillomavirus testing improves the prediction of cervical intraepithelial neoplasia (CIN II-III) in Thai patients with low-grade cytological abnormalities. Asian Pac J Cancer Prev, 12, 1777-83.
  9. Heselmeyer K, Macville M, Schröck E, et al (1997). Advancedstage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q. Genes Chromosomes Cancer, 19, 233-40. https://doi.org/10.1002/(SICI)1098-2264(199708)19:4<233::AID-GCC5>3.0.CO;2-Y
  10. Heselmeyer-Haddad K, Janz V, Castle PE, et al (2003). Detection of genomic amplification of the human telomerase gene (TERC) in cytologic specimens as a genetic test for the diagnosis of cervical dysplasia. Am J Pathol, 163, 1405-16. https://doi.org/10.1016/S0002-9440(10)63498-0
  11. Heselmeyer-Haddad K, Sommerfeld K, White NM, et al (2005). genomic amplification of the human telomerase gene (TERC) in Pap smears predicts the development of cervical cancer. Am J Pathol, 166, 1229-38. https://doi.org/10.1016/S0002-9440(10)62341-3
  12. Heselmeyer K, Schröck E, Manoir du S, et al (1996). Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. Proc Natl Acad Sci U S A, 93, 479-84. https://doi.org/10.1073/pnas.93.1.479
  13. Hopman AH, Theelen W, Hommelberg PP, et al (2006). Genomic integration of oncogene HPV and gain of the human telomerase gene TERC at 3q26 are strongly associated events in the progression of uterine cervical dysplasia to invasive cancer. J Pathol, 210, 412-9. https://doi.org/10.1002/path.2070
  14. Katki HA, Kinney WK, Fetterman B, et al (2011). Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a populationbased study in routine clinical practice. Lancet Oncol, 12, 663-72. https://doi.org/10.1016/S1470-2045(11)70145-0
  15. Kirchhoff M, Rose H, Petersen BL, et al (1999). Comparative genomic hybridization reveals a recurrent pattern of chromosomal aberrations in severe dysplasia/carcinoma in situ of the cervix and in advanced-stage cervical carcinoma. Genes Chromosomes Cancer, 24, 144-50. https://doi.org/10.1002/(SICI)1098-2264(199902)24:2<144::AID-GCC7>3.0.CO;2-9
  16. Policht FA, Song M, Sitailo S, et al (2010). Analysis of genetic copy number changes in cervical disease progression. BMC Cancer, 10, 432. https://doi.org/10.1186/1471-2407-10-432
  17. Poomtavorn Y, Suwannarurk K, Thaweekul Y, et al (2011). Risk factors for high-grade cervical intraepithelial neoplasia in patients with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou smears. Asian Pac J Cancer Prev, 12, 235-8.
  18. Rodriguez AC, Schiffman M, Herrero R, et al (2008). Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J Natl Cancer Inst, 100, 513-7. https://doi.org/10.1093/jnci/djn044
  19. Ronco G, Giorgi-Rossi P, Carozzi F, et al (2010). Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol, 11, 249-57. https://doi.org/10.1016/S1470-2045(09)70360-2
  20. Rosa MI, Fachel JM, Rosa DD, et al (2008). Persistence and clearance of human papillomavirus infection: a prospective cohort study. Am J Obstet Gynecol, 199, 617.
  21. Sokolova I, Algeciras-Schimnich A, et al (2007). Chromosomal biomarkers for detection of human papillomavirus associated with genomic instability in epithelial cells of cervical cytology specimen. J Mol Diagn, 9, 604-11. https://doi.org/10.2353/jmoldx.2007.070007
  22. Solomon D, Nayar R (2004). The Bethesda system for reporting cervical cytology: definitions, criteria and explanatory notes. Springer Science+Business Media, LLC, New York.
  23. Solomon D, Schiffman M, Tarone R, et al (2001). Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst, 93, 293-9. https://doi.org/10.1093/jnci/93.4.293
  24. Tu Z, Zhang A, Wu R, et al (2009). Genomic amplification of the human telomerase RNA gene for differential diagnosis of cervical disorders. Cancer Genet Cytogenet, 191, 10-6. https://doi.org/10.1016/j.cancergencyto.2009.01.004
  25. Umayahara K, Hirai Y, Sugiyama Y, et al (2005). Genetic alterations during the progression of early cervical neoplasm [abstract]. Proc Amer Assoc Cancer Res, 46, 5743.
  26. Voss JS, Kipp BR, Campion MB, et al (2010). Assessment of fluorescence in situ hybridization and hybrid capture 2 analyses of cervical cytology specimens diagnosed as low grade squamous intraepithelial lesion for the detection of high grade cervical intraepithelial neoplasia [abstract]. Anal Quant Cytol Histol, 32, 121-30.
  27. World Health Organization, Department of Reproductive Health and Research and Department of Chronic Diseases and Health Promotion (2006). Comprehensive cervical cancer control: a guide to essential practice. Geneva.
  28. Wright TC Jr, Massad LS, Dunton CJ, et al (2007). 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol, 197, 346-55. https://doi.org/10.1016/j.ajog.2007.07.047
  29. Wright TC Jr, Stoler MH, Sharma A, et al (2011). Evaluation of HPV-16 and HPV-18 Genotyping for the Triage of Women With High-Risk HPV+ Cytology-Negative Results. Am J Clin Pathol, 136, 578-86. https://doi.org/10.1309/AJCPTUS5EXAS6DKZ
  30. Zhang A, Maner S, Betz R, et al (2002). Genetic alterations in cervical carcinomas: frequent low-level amplifications of oncogenes are associated with human papillomavirus infection. Int J Cancer, 101, 427-33. https://doi.org/10.1002/ijc.10627

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