Skip to main content
Log in

Human papillomavirus in high-grade cervical lesions: Austrian data of a European multicentre study

Humane Papilloma Viren in hochgradigen zervikalen Dysplasien: Österreichische Daten einer europäischen multizentrischen Studie

  • original article
  • Published:
Wiener klinische Wochenschrift Aims and scope Submit manuscript

Summary

Background

The purpose is to present the Austrian data of an observational, cross-sectional, multicentre study conducted in 13 European countries. This study was undertaken to assess human papillomavirus (HPV) type distribution in high-grade cervical lesions.

Methods

Two hundred and ninety cases of high-grade cervical intraepithelial neoplasia (CIN2, CIN3) or adenocarcinoma in situ of the cervix from 2004 to 2007 were analysed by histopathological review and polymerase chain reaction for HPV.

Results

Two hundred and nine cases were “histologically eligible” and of those 206 were HPV+. Median age was 34 years (19–76 years). CIN3 was the most frequent diagnosis (64.6 %), followed by CIN2/3 (19.4 %) and CIN2 (13.6 %). Adenocarcinoma in situ was only detected together with a squamous lesion in 2.4 % cases. Majority of women (75.2 %) were infected with a single HPV type, 98.1 % of them with high-risk HPV types: HPV 16 (56.1 %), HPV 33 (12.3 %), HPV 31 (11.0 %), HPV 18 (3.9 %), HPV 35 (3.9 %), HPV 51 (3.2 %) and HPV 52 (2.6 %), HPV 58 (1.9 %) and HPV 45 (0.6 %). The low-risk HPV 6 was found in 1.3 % cases. Forty-six lesions (22.3 %) contained multiple infections, 71.1 % of those were HPV 16 or 18 and 91.1 % were HPV 16, 18, 31, 33 or 45 positive.

Conclusions

These Austrian data clearly demonstrate that HPV 16 is the predominant type in high-grade CIN, the immediate precursor lesions of cervical cancer. More than 60 % of the lesions were associated with HPV 16 and 18 and more than 85 % with HPV 16, 18, 31, 33 or 45. The prevalence of adenocarcinoma in situ is underestimated, since its detection is difficult with the current cytology screening.

Zusammenfassung

Grundlagen

Ziel dieser multizentrischen, in 13 europäischen Ländern durchgeführten Beobachtungsstudie ist die Erfassung der Typenverteilung von Humanen Papilloma Viren (HPV) in hochgradigen zervikalen Läsionen. Es werden die österreichischen Ergebnisse präsentiert.

Methodik

290 Fälle von hochgradigen zervikalen intraepithelialen Neoplasien (CIN2, CIN3) oder Adenocarcinoma in situ der Zervix wurden analysiert. Es wurden retrospektiv (von 2007–2004) zervikale Biopsiepräparate mit hochgradigen zervikalen Neoplasien sequentiell aus dem Archiv enthoben. Nach neuerlicher histopathologischer Prüfung erfolgte eine Testung auf HPV Desoxyribonucleinsäure mittels Polymerase Kettenreaktion.

Ergebnisse

209 Frauen bildeten die „histologisch auswertbare“ Kohorte, 206 waren HPV positiv. Das mittlere Alter war 34 Jahre (19–76). CIN3 war die häufigste histologische Diagnose (64,6 %), gefolgt von CIN2/3 (19,4 %) und CIN2 (13,6 %). Ein Adenocarcinoma in situ der Zervix wurde immer nur in Kombination mit einer hochgradigen Dysplasie diagnostiziert (2,4 %).

Die meisten Frauen waren mit einem HPV Typ infiziert (75,2 %), 98,1 % von diesen mit einem Hochrisiko-Typ: HPV 16 (56,1 %), HPV 33 (12,3 %), HPV 31 (11,0 %), HPV 18 (3,9 %), HPV 35 (3,9 %), HPV 51 (3,2 %) und HPV 52 (2,6 %), HPV 58 (1,9 %) und HPV 45 in 0,6 %. 46 Biopsate wiesen mehrere HPV Typen auf (22,3 %), 71,1 % davon HPV 16 oder 18 und 91,1 % HPV 16, 18, 31, 33 oder 45.

Schlussfolgerungen

HPV 16 ist der vorherrschende HPV Typ in hochgradigen zervikalen Neoplasien, der unmittelbaren Vorstufe des invasiven Zervixkarzinoms. Mehr als 60 % der Läsionen war mit HPV 16 und 18 assoziiert, mehr als 85 % mit HPV 16, 18, 31, 33 oder 45. Die Prävalenz des Adenocarcinoma in situ wird unterschätzt, da es mit den gängigen Screening Methoden schwer zu diagnostizieren ist.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007;370:890–907.

    Article  PubMed  CAS  Google Scholar 

  2. Baseman JG, Koutsky LA. The epidemiology of human papillomavirus infections. J Clin Virol. 2005;32(Suppl 1):S16–24.

    Article  PubMed  Google Scholar 

  3. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55:74–108.

    Article  PubMed  Google Scholar 

  4. Regauer S, Reich O. CK17 and p16 expression patterns distinguish (atypical) immature squamous metaplasia from high-grade cervical intraepithelial neoplasia (CIN III). Histopathology. 2007;50(5):629–35.

    Article  PubMed  CAS  Google Scholar 

  5. Reich O, Pickel H, Regauer S. Why does HPV infection induce sharply demarcated lesions of the cervix? J Low Genit Tract Dis. 2008;12:8–10.

    Article  PubMed  Google Scholar 

  6. Reich O, Pickel H. Multifocal stromal invasion in microinvasive squamous cell carcinoma of the cervix: how to measure and stage these lesions. Int J Gynecol Pathol. 2002;21:416–7.

    Article  PubMed  Google Scholar 

  7. Reich O, Pickel H, Tamussino K, Winter R. Microcarcinoma of the cervix: first focus of invasion. Obstet Gynecol. 2001;97:890–2.

    Article  PubMed  CAS  Google Scholar 

  8. McCredie MR, Sharples KJ, Paul C, et al. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. 2008;9(5):425–34.

    Article  PubMed  Google Scholar 

  9. Smith JS, Lindsay L, Hoots B, et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer. 2007;121:621–32.

    Article  PubMed  CAS  Google Scholar 

  10. Tjalma WA, Fiander A, Reich O, et al.; HERACLES/SCALE Study Group. Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe. Int J Cancer. 2013;132(4):854–67.

    Google Scholar 

  11. Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998;17(8):857–72.

    Article  PubMed  CAS  Google Scholar 

  12. Zechmeister I. Ökonomische Evaluation der Impfung gegen humane Papillomaviren (HPV- Impfung) in Österreich. Endbericht des Ludwig Boltzmann Instituts für Health Technology Assessment (LBI-HTA) 2007;26.

  13. Leitner B. Statistik Austria, Jahrbuch der Gesundheitsstatistik 2010. Vienna: Statistik Austria; 2011.

  14. Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet. 2006;367(9509):489–98.

    Article  PubMed  CAS  Google Scholar 

  15. Arbyn M, Kyrgiou M, Simoens C, et al. Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ. 2008;337:a1284.

    Article  PubMed  CAS  Google Scholar 

  16. Van Hentenryck M, Noel JC, Simon P. Obstetric and neonatal outcome after surgical treatment of cervical dysplasia. Eur J Obstet Gynecol Reprod Biol. 2012;162(1):16–20.

    Article  PubMed  Google Scholar 

  17. Ortoft G, Henriksen T, Hansen E, Petersen L. After conisation of the cervix, the perinatal mortality as a result of preterm delivery increases in subsequent pregnancy. BJOG. 2010;117(3):258–67.

    Article  PubMed  CAS  Google Scholar 

  18. Six L, Leodolter S, Sings HL, Barr E, Haupt R, Joura EA. Prevalence of Human Papillomavirus Types 6, 11, 16, and 18 in young Austrian Women- the baseline data of a Phase III Vaccine Trial. Wien Klin Wochenschr. 2008;120(21–22):666–71.

    Article  PubMed  Google Scholar 

  19. Herzog TJ, Monk BJ. Reducing the burden of glandular carcinomas of the uterine cervix. Am J Obstet Gynecol. 2007;197(6):566–71.

    Article  PubMed  Google Scholar 

  20. Bray F, Carstensen B, Møller H, et al. Incidence trends of adenocarcinoma of the cervix in 13 European countries. Cancer Epidemiol Biomarkers Prev. 2005;14(9):2191–9.

    Article  PubMed  Google Scholar 

  21. Zielonke N. Krebsinzidenz und Krebsmortalität in Österreich 2012. Vienna: Statistik Austria; 2012.

  22. Ault KA, Joura EA, Kjaer SK, et al.; FUTURE I and II Study Group. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine. Int J Cancer. 2011;128(6):1344–53.

    Article  PubMed  CAS  Google Scholar 

  23. Stoler MH, Vichnin MD, Ferenczy A, et al.; FUTURE I, II and III Investigators. The accuracy of colposcopic biopsy: analyses from the placebo arm of the Gardasil clinical trials. Int J Cancer. 2011;128(6):1354–62.

    Article  PubMed  CAS  Google Scholar 

  24. van Doorn LJ, Molijn A, Kleter B, Quint W, Colau B. Highly effective detection of human papillomavirus 16 and 18 DNA by a testing algorithm combining broad-spectrum and type-specific PCR. J Clin Microbiol. 2006;44:3292–8.

    Article  PubMed  Google Scholar 

  25. van Doorn LJ, Quint W, Kleter B, et al. Genotyping of human papillomavirus in liquid cytology cervical specimens by the PGMY line blot assay and the SPF(10) line probe assay. J Clin Microbiol. 2002;40:979–83.

    Article  PubMed  Google Scholar 

  26. Paavonen J, Naud P, Salmerón J, et al.; HPV PATRICIA Study Group. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 2009;374(9686):301–14.

    Article  PubMed  CAS  Google Scholar 

  27. Lehtinen M, Paavonen J, Wheeler CM, et al.; HPV PATRICIA Study Group. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012;13(1):89–99.

    Article  PubMed  CAS  Google Scholar 

  28. FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356:1915–27.

    Article  Google Scholar 

  29. Joura EA, Leodolter S, Hernandez-Avila M, et al. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16 and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three clinical trials. Lancet. 2007;369:1693–702.

    Article  PubMed  CAS  Google Scholar 

  30. Joura EA, Garland SM, Paavonen J, et al.; FUTURE I and II Study Group. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data. BMJ. 2012;27(344):e1401.

    Google Scholar 

  31. Brown DR, Kjaer SK, Sigurdsson K, et al. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16–26 years. J Infect Dis. 2009;199(7):926–35.

    Article  PubMed  Google Scholar 

  32. Wheeler CM, Castellsagué X, Garland SM, et al. HPV PATRICIA Study Group. Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012;13(1):100–10.

    Article  PubMed  CAS  Google Scholar 

  33. Malagón T, Drolet M, Boily MC, et al. Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12(10):781–9.

    Article  PubMed  Google Scholar 

  34. Canfell K, Chesson H, Kulasingam SL, Berkhof J, Diaz M, Kim JJ. Modeling preventative strategies against human papillomavirus-related disease in developed countries. Vaccine. 2012;30 Suppl 5:F157–67.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elmar A. Joura MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rössler, L., Reich, O., Horvat, R. et al. Human papillomavirus in high-grade cervical lesions: Austrian data of a European multicentre study. Wien Klin Wochenschr 125, 591–599 (2013). https://doi.org/10.1007/s00508-013-0403-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00508-013-0403-6

Keywords

Schlüsselwörter

Navigation