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Longitudinal study of patients after surgical treatment for cervical lesions: detection of HPV DNA and prevalence of HPV-specific antibodies

  • R. TachezyEmail author
  • I. Mikyšková
  • V. Ludvíková
  • L. Rob
  • T. Kučera
  • V. Slavík
  • A. Beková
  • H. Robová
  • M. Pluta
  • E. Hamšíková
Article

Abstract

The principal aims of this study were to test whether persistence of human papillomavirus (HPV) DNA is predictive of recurrent disease in women after surgical treatment for cervical lesions, to distinguish between persistent and newly acquired HPV infection, and to observe the effect of surgical treatment on levels of HPV-specific antibodies. A group of 198 patients surgically treated for low-grade and high-grade squamous intraepithelial lesions and 35 age-matched controls were monitored for 18 months at 6-month intervals. The presence of HPV DNA in cervical smears was detected by means of consensus polymerase chain reaction, and serum levels of HPV-specific antibodies to HPV types 16, 18, 31, 33, and 45 were measured. In ten patients positive for HPV type 16 in consecutive samples, the HPV 16 variants were identified using a polymerase chain reaction specific for the long control region. Data regarding demographics, risk factors for cervical cancer, and risks related to HPV exposure were collected through a patient questionnaire. Subjects persistently positive for HPV DNA were more likely to present with cytological and/or colposcopical abnormalities. A higher reactivity to HPV-specific antibodies was observed in these women at the 18-month follow-up visit. All ten patients with HPV 16 infection detected in consecutive samples showed persistence of either the same prototype or the same variant during the follow-up period. Risky sexual behavior and smoking were more common in patients than in controls. Persistent HPV infection as demonstrated by both HPV DNA detection and antibody detection appears to be a risk factor for the recurrence of pathological findings in women after surgery. An individually based approach to surgical treatment is an important factor in the outcome of disease at follow-up.

Keywords

Cervical Cancer Cervical Lesion Consecutive Sample Large Loop Excision Intratype Variation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgement

This study was supported by a grant from the Internal Grant Agency of the Ministry of Health, Czech Republic, grant no. NC 7548-3.

References

  1. 1.
    Bollen LJ, Tjong-A-Hung SP, van der Velden J, Mol BW, ten Kate FW, ter Schegget J, Bleker OP (1999) Prediction of recurrent and residual cervical dysplasia by human papillomavirus detection among patients with abnormal cytology. Gynecol Oncol 72:199–201PubMedCrossRefGoogle Scholar
  2. 2.
    Loizzi P, Carriero C, Di Gesu A, Resta L, Nappi R (1992) Rational use of cryosurgery and cold knife conization for treatment of cervical intraepithelial neoplasia. Eur J Gynaecol Oncol 13:507–513PubMedGoogle Scholar
  3. 3.
    Elfgren K, Bistoletti P, Dillner L, Walboomers JM, Meijer CJ, Dillner J (1996) Conization for cervical intraepithelial neoplasia is followed by disappearance of human papillomavirus deoxyribonucleic acid and a decline in serum and cervical mucus antibodies against human papillomavirus antigens. Am J Obstet Gynecol 174:937–942PubMedCrossRefGoogle Scholar
  4. 4.
    Kanamori Y, Kigawa J, Minagawa Y, Irie T, Oishi T, Itamochi H, Cheng X, Terakawa N (1998) Residual disease and presence of human papillomavirus after conization. Oncology 55:517–520PubMedCrossRefGoogle Scholar
  5. 5.
    Chua KL, Hjerpe A (1997) Human papillomavirus analysis as a prognostic marker following conization of the cervix uteri. Gynecol Oncol 66:108–113PubMedCrossRefGoogle Scholar
  6. 6.
    Nagai Y, Maehama T, Asato T, Kanazawa K (2000) Persistence of human papillomavirus infection after therapeutic conization for CIN 3: is it an alarm for disease recurrence? Gynecol Oncol 79:294–299PubMedCrossRefGoogle Scholar
  7. 7.
    Lin CT, Tseng CJ, Lai CH, Hsueh S, Huang KG, Huang HJ, Chao A (2001) Value of human papillomavirus deoxyribonucleic acid testing after conization in the prediction of residual disease in the subsequent hysterectomy specimen. Am J Obstet Gynecol 184:940–945PubMedCrossRefGoogle Scholar
  8. 8.
    Zielinski GD, Bais AG, Helmerhorst TJ, Verheijen RH, de Schipper FA, Snijders PJ, Voorhorst FJ, van Kemenade FJ, Rozendaal L, Meijer CJ (2004) HPV testing and monitoring of women after treatment of CIN 3: review of the literature and meta-analysis. Obstet Gynecol Surv 59:543–553PubMedCrossRefGoogle Scholar
  9. 9.
    Ho GY, Burk RD, Klein S, Kadish AS, Chang CJ, Palan P, Basu J, Tachezy R, Lewis R, Romney S (1995) Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia. J Natl Cancer Inst 87:1365–1371PubMedCrossRefGoogle Scholar
  10. 10.
    IARC Working Group (1995) Human papillomaviruses. IARC, Lyon, FranceGoogle Scholar
  11. 11.
    Liaw KL, Glass AG, Manos MM, Greer CE, Scott DR, Sherman M, Burk RD, Kurman RJ, Wacholder S, Rush BB, Cadell DM, Lawler P, Tabor D, Schiffman M (1999) Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions. J Natl Cancer Inst 91:954–960PubMedCrossRefGoogle Scholar
  12. 12.
    Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19PubMedCrossRefGoogle Scholar
  13. 13.
    de Roda Husman AM, Walboomers JM, Meijer CJ, Risse EK, Schipper ME, Helmerhorst TM, Bleker OP, Delius H, van den Brule AJ, Snijders PJ (1994) Analysis of cytomorphologically abnormal cervical scrapes for the presence of 27 mucosotropic human papillomavirus genotypes, using polymerase chain reaction. Int J Cancer 56:802–806PubMedCrossRefGoogle Scholar
  14. 14.
    Ho L, Chan S-Y, Burk RD, Das BC, Fujinaga K, Icenogle JP, Kahn T, Kiviat N, Lancaster W, Mavromara-Nazos P, Labropoulou V, Mitrani-Rosenbaum S, Norrild B, Pillai MR, Stoerker J, Syrjänen K, Syrjänen SM, Tay S-K, Villa LL, Wheeler CM, Williamson A-L, Bernard H-U (1993) The genetic drift of human papillomavirus type 16 is a means of reconstructing prehistoric viral spread and the movement of ancient human populations. J Virol 67:6413–6423PubMedGoogle Scholar
  15. 15.
    Tornesello ML, Buonaguro FM, Meglio A, Buonaguro L, Beth GE, Giraldo G (1997) Sequence variations and viral genomic state of human papillomavirus type 16 in penile carcinomas from Ugandan patients. J Gen Virol 78:2199–2208PubMedGoogle Scholar
  16. 16.
    Yamada T, Wheeler CM, Halpern AL, Stewart AC, Hildesheim A, Jenison SA (1995) Human papillomavirus type 16 variant lineages in United States populations characterized by nucleotide sequence analysis of the E6, L2, and L1 coding segments. J Virol 69:7743–7753PubMedGoogle Scholar
  17. 17.
    Yamada T, Manos MM, Peto J, Greer CE, Munoz N, Bosch FX, Wheeler CM (1997) Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide perspective. J Virol 71:2463–2472PubMedGoogle Scholar
  18. 18.
    Xi LF, Koutsky LA, Galloway DA, Kuypers J, Hughes JP, Wheeler CM, Holmes KK, Kiviat NB (1997) Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia. J Natl Cancer Inst 89:796–802PubMedCrossRefGoogle Scholar
  19. 19.
    Hildesheim A, Wang SS (2002) Host and viral genetics and risk of cervical cancer: a review. Virus Res 89:229–240PubMedCrossRefGoogle Scholar
  20. 20.
    Tornesello ML, Duraturo ML, Salatiello I, Buonaguro L, Losito S, Botti G, Stellato G, Greggi S, Piccoli R, Pilotti S, Stefanon B, De PG, Franceschi S, Buonaguro FM (2004) Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer. J Med Virol 74:117–126PubMedCrossRefGoogle Scholar
  21. 21.
    Franco EL, Villa LL, Rahal P, Ruiz A (1994) Molecular variant analysis as an epidemiological tool to study persistence of cervical human papillomavirus infection. J Natl Cancer Inst 86:1558–1559PubMedCrossRefGoogle Scholar
  22. 22.
    van Belkum A, Juffermans L, Schrauwen L, van Doornum G, Burger M, Quint W (1995) Genotyping human papillomavirus type 16 isolates from persistently infected promiscuous individuals and cervical neoplasia patients. J Clin Microbiol 33:2957–2962PubMedGoogle Scholar
  23. 23.
    Tachezy R, Hamsikova E, Hajek T, Mikyskova I, Smahel M, Van Ranst M, Kanka J, Havrankova A, Rob L, Guttner V, Slavik V, Anton M, Kratochvil B, Kotrsova L, Vonka V (1999) Human papillomavirus genotype spectrum in Czech women: correlation of HPV DNA presence with antibodies against HPV-16, 18, and 33 virus-like particles. J Med Virol 58:378–386PubMedCrossRefGoogle Scholar
  24. 24.
    Bauer HM, Ting Y, Greer CE, Chambers JC, Tashiro CJ, Chimera J, Reingold A, Manos MM (1991) Genital human papillomavirus infection in female university students as determined by a PCR-based method. JAMA 265:472–477PubMedCrossRefGoogle Scholar
  25. 25.
    Xi LF, Demers W, Kiviat NB, Kuypers J, Beckmann AM, Galloway DA (1993) Sequence variation in the noncoding region of human papillomavirus type 16 detected by single-strand conformation polymorphism analysis. J Infect Dis 168:610–617PubMedGoogle Scholar
  26. 26.
    Hamšíková E, Ludvíková V, Šmahel M, Sapp M, Vonka V (1998) Prevalence of antibodies to human papillomaviruses in the general population of the Czech Republic. Int J Cancer 77:689–694PubMedCrossRefGoogle Scholar
  27. 27.
    IARC Working Group (2005) IARC handbooks of cancer prevention: cervix cancer screening. IARC, Lyon, FranceGoogle Scholar
  28. 28.
    Chao A, Lin CT, Hsueh S, Chou HH, Chang TC, Chen MY, Lai CH (2004) Usefulness of human papillomavirus testing in the follow-up of patients with high-grade cervical intraepithelial neoplasia after conization. Am J Obstet Gynecol 190:1046–1051PubMedCrossRefGoogle Scholar
  29. 29.
    Houfflin Debarge V, Collinet P, Vinatier D, Ego A, Dewilde A, Boman F, Leroy JL (2003) Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions. Gynecol Oncol 90:587–592PubMedCrossRefGoogle Scholar
  30. 30.
    Nobbenhuis MA, Helmerhorst TJ, van den Brule AJ, Rozendaal L, Voorhorst FJ, Bezemer PD, Verheijen RH, Meijer CJ (2001) Cytological regression and clearance of high-risk human papillomavirus in women with an abnormal cervical smear. Lancet 358:1782–1783PubMedCrossRefGoogle Scholar
  31. 31.
    Hamšíková E, Ludvíková V, Tachezy R, Kovařík J, Břoušková L, Vonka V (2000) Longitudinal follow-up of antibody response to selected antigens of human papillomaviruses and herpes viruses in patients with invasive cervical carcinoma. Int J Cancer 86:351–355PubMedCrossRefGoogle Scholar
  32. 32.
    Dillner J (1993) Disappearance of antibodies to HPV 16 E7 after treatment for cervical cancer. Lancet 341:1594PubMedCrossRefGoogle Scholar
  33. 33.
    Fisher SG, Benitez-Bribiesca L, Nindl I, Stockfleth E, Muller M, Wolf H, Perez-Garcia F, Guzman-Gaona J, Gutierrez-Delgado F, Irvin W, Gissmann L (1996) The association of human papillomavirus type 16 E6 and E7 antibodies with stage of cervical cancer. Gynecol Oncol 61:73–78PubMedCrossRefGoogle Scholar
  34. 34.
    Baay MFD, Duk JM, Burger MPM, Debruijn HWA, Stolz E, Herbrink P (1999) Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up. Eur J Clin Microbiol Infect Dis 18:126–132PubMedCrossRefGoogle Scholar
  35. 35.
    Xi LF, Demers W, Kiviat NB, Kuypers J, Beckmann AM, Galloway DA (1993) Sequence variation in the noncoding region of human papillomavirus type 16 detected by single-strand conformation polymorphism analysis. J Infect Dis 168:610–617PubMedGoogle Scholar
  36. 36.
    Mayrand MH, Coutlee F, Hankins C, Lapointe N, Forest P, de Ladurantaye M, Roger M (2000) Detection of human papillomavirus type 16 DNA in consecutive genital samples does not always represent persistent infection as determined by molecular variant analysis. J Clin Microbiol 38:3388–3393PubMedGoogle Scholar
  37. 37.
    Londesborough P, Ho L, Terry G, Cuzick J, Wheeler C, Singer A (1996) Human papillomavirus genotype as a predictor of persistence and development of high-grade lesions in women with minor cervical abnormalities. Int J Cancer 69:364–368PubMedCrossRefGoogle Scholar
  38. 38.
    Zehbe I, Wilander E, Delius H, Tommasino M (1998) Human papillomavirus 16 E6 variants are more prevalent in invasive cervical carcinoma than the prototype. Cancer Res 58:829–833PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • R. Tachezy
    • 1
    Email author
  • I. Mikyšková
    • 1
  • V. Ludvíková
    • 1
  • L. Rob
    • 2
  • T. Kučera
    • 1
  • V. Slavík
    • 3
  • A. Beková
    • 3
  • H. Robová
    • 2
  • M. Pluta
    • 2
  • E. Hamšíková
    • 1
  1. 1.Department of Experimental VirologyInstitute of Hematology and Blood TransfusionPrague 2Czech Republic
  2. 2.Obstetrics and Gynecology Clinic, Department of Oncogynecology, Second Medical FacultyCharles UniversityPrague 5Czech Republic
  3. 3.Centre of Gynecology-Oncology PreventionPrague 2Czech Republic

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