Telomerase Activity and HPV Infection in Cervical Smears of Women With High Grade Squamous Intraephitelial Lesions. A Follow-up study
Keywords:
Human papillomavirus, telomerase, cervical cancer, follow-up studiesAbstract
Objective: To describe telomerase activity (TA) and HPV infectionin follow up of women in the Bogotá cohort.
Methods: Analysiswas carried out on 79 follow up samples from 25 women who developed LEI-AG, and 149 follow up samples from 34 women with normal cytology. HPV detection was made with PCR-EIA GP5+/GP6+ and RLB. TA was measured with TRAP-ELISA.
Results: Analysis revealed that out of the 25 cases, 8 were prevalent (enrolled in the study with LEI-AG), and the remaining 17 incidental (lesion was detected during follow up). Among these 17 women, 12 (70.5%) had, at diagnosis or during a previous checkup, TA and high-risk HPV (HPV-AR), primarily type α-9. Three women (17.7%) had transitory HPV infections, and 2 (11.8%) had neither HPV nor TA at diagnosis. Follow up on women with normal cytology revealed that only eight women (23.5%) had HPV and TA at the same time, 21/34 women (61.8%) had transitory HPV event during follow up,and 5(14.7%) hadno HPV during entirety of follow up.
Conclusions: Detection of TA and simultaneous HPV-AR infection apparently predicts LEI-AR risk.
Author Biographies
Carolina Martín, Instituto Nacional de Cancerología
Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Gustavo Hernández, Instituto Nacional de Cancerología
Grupo de Investigación Epidemiológica, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Óscar Gamboa, Instituto Nacional de Cancerología
Grupo de Investigación Epidemiológica, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Óscar Buitrago, Instituto Nacional de Cancerología
Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Mauricio González, Instituto Nacional de Cancerología
Grupo de Ginecología, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Nubia Muñoz, Instituto Nacional de Cancerología
Grupo de Investigación Epidemiológica, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Mónica Molano, Instituto Nacional de Cancerología
Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
References
Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010 ;127:2893-917.
https://doi.org/10.1002/ijc.25516
Hiyama E, Kodama T, Shinbara K, et al. Telomerase activity is detected in pancreatic cancer but not in benign tumors. Cancer Res. 1997;57:326-31.
Hiyama K, Hiyama E, Ishioka S, et al. Telomerase activity in small-cell and non-small-cell lung cancers. J Natl Cancer Inst. 1995;87:895-902.
https://doi.org/10.1093/jnci/87.12.895
Kawai J, Kodera Y, Fujiwara M, et al. Telomerase activity as prognostic factor in gastrointestinal stromal tumors of the stomach. Hepatogastroenterology. 2005;52:959-64.
Nouso K, Urabe Y, Higashi T, et al. Telomerase as a tool for the differential diagnosis of human hepatocellular carcinoma. Cancer. 1996;78:232-6.
https://doi.org/10.1002/(SICI)1097-0142(19960715)78:2<232::AID-CNCR7>3.0.CO;2-N
Sommerfeld HJ, Meeker AK, Piatyszek MA, et al. Telomerase activity: a prevalent marker of malignant human prostate tissue. Cancer Res. 1996;56:218-22.
Taylor RS, Ramírez RD, Ogoshi M, et al. Detection of telomerase activity in malignant and nonmalignant skin conditions. J Invest Dermatol. 1996;106:759-65.
https://doi.org/10.1111/1523-1747.ep12345811
Molano M, Posso H, Weiderpass E, et al., Prevalence and determinants of HPV infection among Colombian women with normal cytology. Br J Cancer. 2002;87:324-33.
https://doi.org/10.1038/sj.bjc.6600442
Jacobs MV, Snijders PJ, van den Brule AJ, et al. A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. J Clin Microbiol. 1997;35:791-5.
https://doi.org/10.1128/JCM.35.3.791-795.1997
van den Brule AJ, Pol R, Fransen-Daalmeijer N, et al. GP5+/6+ PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes. J Clin Microbiol. 2002;40:779-87
https://doi.org/10.1128/JCM.40.3.779-787.2002
Ault KA, Allen HK, Phillips SL, et al. Telomerase activity as a potential diagnostic marker for triage of abnormal Pap smears. J Low Genit Tract Dis. 2005;9:93-9.
https://doi.org/10.1097/00128360-200504000-00005
ROCHE, Applied Science. Instruction Manual: Telo TAGGG Telomerase PCR ELISA Cat. No. 11854666910. 1-21. 1-11-2004.Ref Type: Generic
Kjær SK, Frederiksen K, Munk C, et al. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst. 2010;102:1478-88.
https://doi.org/10.1093/jnci/djq356
Sundström K, Eloranta S, Sparén P, et al. Prospective study of human papillomavirus (HPV) types, HPV persistence, and risk of squamous cell carcinoma of the cervix. Cancer Epidemiol Biomarkers Prev. 2010;19:2469-78.
https://doi.org/10.1158/1055-9965.EPI-10-0424
Muñoz N, Hernández-Suárez G, Méndez F, et al. Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women. Br J Cancer. 2009;100:1184-90.
https://doi.org/10.1038/sj.bjc.6604972
Mesher D, Szarewski A, Cadman L, et al. Long-term follow- up of cervical disease in women screened by cytology and HPV testing: results from the HART study. Br J Cancer. 2010;102:1405-10.
https://doi.org/10.1038/sj.bjc.6605619
Monnier-Benoit S, Dalstein V, Riethmuller D, et al. Dynamics of HPV16 DNA load reflect the natural history of cervical HPV-associated lesions. J Clin Virol. 2006;35:270-7.
https://doi.org/10.1016/j.jcv.2005.09.001
Snijders PJ, Hogewoning CJ, Hesselink AT, et al. Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33-positive women with normal cytology. Int J Cancer. 2006;119:1102-7.
https://doi.org/10.1002/ijc.21956
Sharma A, Rajappa M, Saxena A, et al. Telomerase activity as a tumour marker in Indian women with cervical intraepithelial neoplasia and cervical cancer. Mol Diagn Ther. 2007;11:193-201.
https://doi.org/10.1007/BF03256241
Skvortsov DA, Gasparian NM, Rubtsova MP, et al. Telomerase as a potential marker for early diagnosing cervical carcinoma. Dokl Biochem Biophys. 2006;408:158-60.
https://doi.org/10.1134/S1607672906030148
Katzenellenbogen RA, Egelkrout EM, VlietαGregg P, et al. NFX1α123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells. J Virol. 2007;81:3786-96.
https://doi.org/10.1128/JVI.02007-06
Lee D, Kim HZ, Jeong KW, et al. Human papillomavirus E2 downαregulates the human telomerase reverse transcriptase promoter. J Biol Chem. 2002;277:2774856.
https://doi.org/10.1074/jbc.M203706200
Ding DC, Chiang MH, Lai HC, et al. Methylation of the long control region of HPV16 is related to the severity of cervical neoplasia. Eur J Obstet Gynecol Reprod Biol. 2009;147:215-20.
https://doi.org/10.1016/j.ejogrb.2009.08.023
Fernández AF, Rosales C, Lopez-Nieva P, et al. The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer. Genome Res. 2009;19:438-51.
https://doi.org/10.1101/gr.083550.108
Kalantari M, Villa LL, Calleja-Macias IE, et al. Human papillomavirus-16 and -18 in penile carcinomas: DNA methylation, chromosomal recombination and genomic variation. Int J Cancer. 2008;123:1832-40.
https://doi.org/10.1002/ijc.23707
Viokurova S, von Knebel DM. Differential methylation of the HPV 16 upstream regulatory region during epithelial differentiation and neoplastic transformation 2011. PLoS ONE. 2011;6:e24451.
https://doi.org/10.1371/journal.pone.0024451
Renaud S, Loukinov D, Bosman FT, et al. CTCF binds the proximal exonic region of hTERT and inhibits its transcription. Nucleic Acids Res. 2005;33:6850-60.
https://doi.org/10.1093/nar/gki989
de Wilde J, Kooter JM, Overmeer RM, et al. hTERT promoter activity and CpG methylation in HPV-induced carcinogénesis. BMC Cancer. 2010;10:271.
https://doi.org/10.1186/1471-2407-10-271
Veldman T, Liu X, Yuan H, et al. Human papillomavirus E6 and Myc proteins associate in vivo and bind to and cooperatively activate the telomerase reverse transcriptase promoter. Proc Natl Acad Sci USA. 2003;100:8211-6.
https://doi.org/10.1073/pnas.1435900100
Riethdorf S, Riethdorf L, Schulz G, et al. Relationship between telomerase activation and HPV 16/18 oncogene expression in squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix. Int J Gynecol Pathol. 2001;20:177-85.
https://doi.org/10.1097/00004347-200104000-00011
Ornish D, Lin J, Daubenmier J, et al. Increased telomerase activity and comprehensive lifestyle changes: a pilot study. Lancet Oncol. 2008;9:1048-57.
https://doi.org/10.1016/S1470-2045(08)70234-1
Mead MN. Molecular biology: telomerase tells on lifestyle. Environ Health Perspect 2008;116:A521.
https://doi.org/10.1289/ehp.116-a521
Heselmeyer-Haddad K, Sommerfeld K, White NM, et al. Genomic amplification of the human telomerase gene (TERC) in pap smears predicts the development of cervical cancer. Am J Pathol. 2005;166:1229-38.
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