Actividad de la telomerasa e infección por VPH en raspados cervicales de mujeres que desarrollaron lesiones escamosas intraepiteliales de alto grado. Un estudio de seguimiento

Información del artículo

Resumen

Objetivo

Describir la AT y la infeccion por VPH en el seguimiento de mujeres que pertenecen a la cohorte de Bogota.

Métodos

Se analizaron 79 muestras del seguimiento de 25 mujeres que desarrollaron LEI-AG y 149 muestras del seguimiento de 34 mujeres con citologia normal. La deteccion del VPH se realizo usando PCR-EIA GP5+/GP6+ y RLB. La AT se midio mediante TRAP-ELISA.

Resultados

El analisis mostro que de los 25 casos, 8 fueron casos prevalentes (ingresaron al estudio con la LEI-AG) y los 17 casos restantes fueron incidentes (la lesion se detecto durante el seguimiento). De estas 17 mujeres, 12 (70,5%) presentaron AT y VPH al momento del diagnostico o en una visita previa, con VPH de alto riesgo (VPH-AR), principalmente de la especie α-9. Tres mujeres (17,7%) mostraron infecciones transitorias por VPH y 2 (11,8%) no tuvieron VPH o AT al diagnostico. El seguimiento de la mujeres con citologia normal mostro que solo ocho mujeres tuvieron VPH y AT al mismo tiempo (23,5%), 21/34 mujeres (61,8%) tuvieron eventos transitorios de VPH durante el seguimiento y 5 (14,7%) no tuvieron VPH durante todo el seguimiento.

Conclusiones

Detectar AT e infeccion por VPH-AR al mismo tiempo parecen predecir el riesgo de LEI-AG.

Palabras clave:

virus del papiloma humano

telomerasa

cancer de cuello uterino

estudios de seguimiento

Abstract

Objective

To describe telomerase activity (TA) and HPV infection in follow up of women in the Bogota cohort.

Methods

Analysis was 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%) had no HPV during entirety of follow up.

Conclusions

Detection of TA and simultaneous HPV-AR infection apparently predicts LEI-AR risk.

Key words:

Human papillomavirus

telomerase

cervical cancer

follow-up studies

El Texto completo está disponible en PDF

Referencias

[1.]

J. Ferlay, H.R. Shin, F. Bray, et al.

Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.

Int J Cancer, 127 (2010), pp. 2893-2917

http://dx.doi.org/10.1002/ijc.25516 | Medline

[2.]

E. Hiyama, T. Kodama, K. Shinbara, et al.

Telomerase activity is detected in pancreatic cancer but not in benign tumors.

Cancer Res, 57 (1997), pp. 326-331

Medline

[3.]

K. Hiyama, E. Hiyama, S. Ishioka, et al.

Telomerase activity in small-cell and non-small-cell lung cancers.

J Natl Cancer Inst, 87 (1995), pp. 895-902

Medline

[4.]

J. Kawai, Y. Kodera, M. Fujiwara, et al.

Telomerase activity as prognostic factor in gastrointestinal stromal tumors of the stomach.

Hepatogastroenterology, 52 (2005), pp. 959-964

Medline

[5.]

K. Nouso, Y. Urabe, T. Higashi, et al.

Telomerase as a tool for the differential diagnosis of human hepatocellular carcinoma.

Cancer, 78 (1996), pp. 232-236

http://dx.doi.org/10.1002/(SICI)1097-0142(19960715)78:2<232::AID-CNCR7>3.0.CO;2-N | Medline

[6.]

H.J. Sommerfeld, A.K. Meeker, M.A. Piatyszek, et al.

Telomerase activity: a prevalent marker of malignant human prostate tissue.

Cancer Res, 56 (1996), pp. 218-222

Medline

[7.]

R.S. Taylor, R.D. Ramirez, M. Ogoshi, et al.

Detection of telomerase activity in malignant and nonmalignant skin conditions.

J Invest Dermatol, 106 (1996), pp. 759-765

Medline

[8.]

M. Molano, H. Posso, E. Weiderpass, et al.

Prevalence and determinants of HPV infection among Colombian women with normal cytology.

Br J Cancer, 87 (2002), pp. 324-333

http://dx.doi.org/10.1038/sj.bjc.6600442 | Medline

[9.]

M.V. Jacobs, P.J. Snijders, A.J. van den Brule, 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, 35 (1997), pp. 791-795

Medline

[10.]

A.J. van den Brule, R. Pol, N. Fransen-Daalmeijer, et al.

GP5+/6+ PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes.

J Clin Microbiol, 40 (2002), pp. 779-787

Medline

[11.]

K.A. Ault, H.K. Allen, S.L. Phillips, et al.

Telomerase activity as a potential diagnostic marker for triage of abnormal Pap smears.

J Low Genit Tract Dis, 9 (2005), pp. 93-99

Medline

[12.]

ROCHE, Applied Science. Instruction Manual: Telo TAGGG Telomerase PCR ELISA Cat. No. 11854666910. 1-21. 1-11-2004.Ref Type: Generic

[13.]

S.K. Kjar, K. Frederiksen, C. Munk, 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, 102 (2010), pp. 1478-1488

http://dx.doi.org/10.1093/jnci/djq356 | Medline

[14.]

K. Sundstrom, S. Eloranta, P. Sparen, et al.

Prospective study of human papillomavirus (HPV) types, HPV persistence, and risk of squamous cell carcinoma of the cervix.

Cancer Epidemiol Biomarkers Prev, 19 (2010), pp. 2469-2478

http://dx.doi.org/10.1158/1055-9965.EPI-10-0424 | Medline

[15.]

N. Munoz, G. Hernandez-Suarez, F. Mendez, et al.

Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women.

Br J Cancer, 100 (2009), pp. 1184-1190

http://dx.doi.org/10.1038/sj.bjc.6604972 | Medline

[16.]

D. Mesher, A. Szarewski, L. Cadman, et al.

Long-term followup of cervical disease in women screened by cytology and HPV testing: results from the HART study.

Br J Cancer, 102 (2010), pp. 1405-1410

http://dx.doi.org/10.1038/sj.bjc.6605619 | Medline

[17.]

S. Monnier-Benoit, V. Dalstein, D. Riethmuller, et al.

Dynamics of HPV16 DNA load reflect the natural history of cervical HPV-associated lesions.

J Clin Virol, 35 (2006), pp. 270-277

http://dx.doi.org/10.1016/j.jcv.2005.09.001 | Medline

[18.]

P.J. Snijders, C.J. Hogewoning, A.T. Hesselink, 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, 119 (2006), pp. 1102-1107

http://dx.doi.org/10.1002/ijc.21956 | Medline

[19.]

A. Sharma, M. Rajappa, A. Saxena, et al.

Telomerase activity as a tumour marker in Indian women with cervical intraepithelial neoplasia and cervical cancer.

Mol Diagn Ther, 11 (2007), pp. 193-201

Medline

[20.]

D.A. Skvortsov, N.M. Gasparian, M.P. Rubtsova, et al.

Telomerase as a potential marker for early diagnosing cervical carcinoma.

Dokl Biochem Biophys, 408 (2006), pp. 158-160

Medline

[21.]

R.A. Katzenellenbogen, E.M. Egelkrout, P. Vliet-Gregg, et al.

NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells.

J Virol, 81 (2007), pp. 3786-3796

http://dx.doi.org/10.1128/JVI.02007-06 | Medline

[22.]

D. Lee, H.Z. Kim, K.W. Jeong, et al.

Human papillomavirus E2 down-regulates the human telomerase reverse transcriptase promoter.

J Biol Chem, 277 (2002),

http://dx.doi.org/10.1074/jbc.M205615200 | Medline

[23.]

D.C. Ding, M.H. Chiang, H.C. Lai, et al.

Methylation of the long control region of HPV16 is related to the severity of cervical neoplasia.

Eur J Obstet Gynecol Reprod Biol, 147 (2009), pp. 215-220

http://dx.doi.org/10.1016/j.ejogrb.2009.08.023 | Medline

[24.]

A.F. Fernandez, C. Rosales, P. Lopez-Nieva, et al.

The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer.

Genome Res, 19 (2009), pp. 438-451

http://dx.doi.org/10.1101/gr.083550.108 | Medline

[25.]

M. Kalantari, L.L. Villa, I.E. Calleja-Macias, et al.

Human papillomavirus-16 and -18 in penile carcinomas: DNA methylation, chromosomal recombination and genomic variation.

Int J Cancer, 123 (2008), pp. 1832-1840

http://dx.doi.org/10.1002/ijc.23707 | Medline

[26.]

S. Viokurova, D.M. von Knebel.

Differential methylation of the HPV 16 upstream regulatory region during epithelial differentiation and neoplastic transformation 2011.

PLoS ONE, 6 (2011), pp. e24451

http://dx.doi.org/10.1371/journal.pone.0024451 | Medline

[27.]

S. Renaud, D. Loukinov, F.T. Bosman, et al.

CTCF binds the proximal exonic region of hTERT and inhibits its transcription.

Nucleic Acids Res, 33 (2005), pp. 6850-6860

http://dx.doi.org/10.1093/nar/gki989 | Medline

[28.]

J. de Wilde, J.M. Kooter, R.M. Overmeer, et al.

hTERT promoter activity and CpG methylation in HPV-induced carcinogenesis.

BMC Cancer, 10 (2010), pp. 271

http://dx.doi.org/10.1186/1471-2407-10-271 | Medline

[29.]

T. Veldman, X. Liu, H. Yuan, 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, 100 (2003), pp. 8211-8216

http://dx.doi.org/10.1073/pnas.1435900100 | Medline

[30.]

S. Riethdorf, L. Riethdorf, G. Schulz, 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, 20 (2001), pp. 177-185

Medline

[31.]

D. Ornish, J. Lin, J. Daubenmier, et al.

Increased telomerase activity and comprehensive lifestyle changes: a pilot study.

Lancet Oncol, 9 (2008), pp. 1048-1057

http://dx.doi.org/10.1016/S1470-2045(08)70234-1 | Medline

[32.]

M.N. Mead.

Molecular biology: telomerase tells on lifestyle.

Environ Health Perspect, 116 (2008), pp. A521

[33.]