European Archives of Oto-Rhino-Laryngology

, Volume 271, Issue 5, pp 1135–1142

Clinical efficiency of quadrivalent HPV (types 6/11/16/18) vaccine in patients with recurrent respiratory papillomatosis



The aim of the study was to assess the clinical efficiency of quadrivalent HPV (types 6/11/16/18) vaccine in patients with recurrent respiratory papillomatosis (RRP). This was a prospective study of patients with RRP treated from January 2009 to July 2012 at the Ear, Nose and Throat Department of the Emergency County Hospital of Cluj-Napoca, Romania. Demographic characteristics, onset of RRP, HPV typing, use and number of cidofovir injections, number of surgeries for RRP per year, and use of human papillomavirus vaccine (types 6, 11, 16, 18) (recombinant, adsorbed)/Silgard® were considered from all the patients included in the study. Charts were reviewed for follow-up after diagnosis, after cidofovir, and after Silgard; all the statistical tests were applied at a significance level of 5 %. The recurrences were observed within 27.53 ± 11.24 days after intralesional cidofovir injection. Thirteen patients with recurrence after cidofovir agreed and received Silgard® vaccine. 85 % [54.44–99.41] of patients had no recurrences during 1-year follow-up. The recurrence of papillomas was observed in two patients (15 %, 95 % CI [0.59–45.56]), one with adult-onset RRP and one with juvenile-onset RRP. Both recurrences appeared after the first Silgard dose; one month after the third vaccine dose each patient underwent a new surgery for remaining papillomas with no recurrences at 1-year follow-up visit. Silgard® vaccination had a good effect and proved to be efficient in the treatment of our patients with RRR without appearance of recurrence in 85 % of the patients during 1-year follow-up.


Recurrent respiratory papillomatosis (RRP) Silgard Recurrence 


  1. 1.
    Newall AT, Brotherson JML, Quinn HE et al (2008) Population seroprevalence of human papillomavirus types 6, 11, 16, and 18 in men, women, and children in Australia. Clin Infect Diseas 46(11):1647–1655CrossRefGoogle Scholar
  2. 2.
    Freed GL, Derkay CS (2006) Prevention of recurrent respiratory papillomatosis: role of HPV vaccination. Inter J Ped Otorhinolaryngol 70(10):1799–1803CrossRefGoogle Scholar
  3. 3.
    Bonagura VR, Hatam LJ, Rosenthal DW, DeVoti JA, Lam F, Steinberg BM, Abramson AL (2010) Recurrent respiratory papillomatosis: a complex defect in immune responsiveness to human papillomavirus-6 and -11. APMIS 118(6–7):455–470PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Hoff SR, Koltai PJ (2012) Operative management of juvenile-onset recurrent respiratory papillomatosis. Oper Tech Otolaryngol 23:117–123CrossRefGoogle Scholar
  5. 5.
    Peng S, Best SR, Hung CF et al (2010) Characterization of human papillomavirus type 11—specific immune responses in a preclinical model. Laryngoscope 120(3):504–510PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Blumin JH, Handler EB, Simpson CB, Osipov V, Merati AL (2009) Dysplasia in adults with recurrent respiratory papillomatosis: incidence and risk factors. Ann Otol Rhinol Laryngol 118(7):481–485PubMedGoogle Scholar
  7. 7.
    Derkay CS (1995) Task force on recurrent respiratory papillomas. A preliminary report. Arch Otolaryngol Head Neck Surg 121(12):1386–1391PubMedCrossRefGoogle Scholar
  8. 8.
    Armstrong LR, Derkay CS, Reeves WC (1999) Initial results from the national registry for juvenile-onset recurrent respiratory papillomatosis. RRP task force. Arch Otolaryngol Head Neck Surg 125(7):743–748PubMedCrossRefGoogle Scholar
  9. 9.
    Mammas IN, Sourvinos G, Spandidos A (2009) Human papilloma virus (HPV) infection in children and adolescents. Eur J Pediatr 168(3):267–273PubMedCrossRefGoogle Scholar
  10. 10.
    Clark L, MacKenzie K (1996) Recurrent respiratory papillomatosis: current knowledge and treatment. Papillomavirus Rep 7:113–118Google Scholar
  11. 11.
    Tjon Pian Gi RE, Dietz A, Djukic V, Eckel HE, Friedrich G, Golusinski W, Hantzakos A, Lawson G, Remacle M, Rihkanen H, Dikkers FG (2012) Treatment of recurrent respiratory papillomatosis and adverse reactions following off-label use of cidofovir (Vistide®). Eur Arch Otorhinolaryngol 269(2):361–362PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Graupp M, Gugatschka M, Kiesler K, Reckenzaun E, Hammer G, Friedrich G (2013) Experience of 11 years use of cidofovir in recurrent respiratory papillomatosis. Eur Arch Otorhinolaryngol 270(2):641–646PubMedCrossRefGoogle Scholar
  13. 13.
    Tjon Pian Gi REA, Ilmarinen T, van den Heuvel ER, Aaltonen LM et al (2013) Safety of intralesional cidofovir in patients with recurrent respiratory papillomatosis: an international retrospective study on 635 RRP patients. Eur Arch Otorhinolaryngol 270(5):1679–1687PubMedCrossRefGoogle Scholar
  14. 14.
    Főrster G, Boltze C, Seidel J, Pawlita M, Mőller A (2008) Juvenile larynxpapillomatose—impfung mit dem polyvalenten Spaltimpfstoff Gardasil®. Laryngo-Rhino-Otol 87(11):796–799CrossRefGoogle Scholar
  15. 15.
    Gillen D (2011) Direct healthcare professional communication regarding serious adverse reactions following off-label use of Vistide.
  16. 16.
    Barr E, Tamms G (2007) Quadrivalent human papillomavirus vaccine. Clin Infect Diseases 45(5):609–617CrossRefGoogle Scholar
  17. 17.
    Jäntschi L, Bolboacă SD (2010) Exact probabilities and confidence limits for binomial samples: applied to the difference between two proportions. Sci World J 18(10):865–878CrossRefGoogle Scholar
  18. 18.
    Hermann JS, Pontes P, Weckx LLM, Fujita R, Avelino M, Pignatari SSN (2012) Laryngeal sequelae of recurrent respiratory papillomatosis surgery in children. Rev Assoc Med Bras 58(2):204–208PubMedCrossRefGoogle Scholar
  19. 19.
    Aaltonen LM, Rihkanen H, Vaheri A (2002) Human papilloma virus in larynx. Laryngoscope 112(4):700–707PubMedCrossRefGoogle Scholar
  20. 20.
    Rahbar R, Vargas SO, Folkman J et al (2005) Role of vascular endothelial growth factor-A in recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol 114(4):289–295PubMedGoogle Scholar
  21. 21.
    Rosen CA, Bryson PC (2004) Indole-3-carbinol for recurrent respiratory papillomatosis: long-term results. J Voice 18(2):248–253PubMedCrossRefGoogle Scholar
  22. 22.
    Soma MA, Albert DM (2008) Cidofovir: to use or not to use? Curr Opin Otolaryngol Head Neck Surg 16(1):86–90PubMedCrossRefGoogle Scholar
  23. 23.
    Donne AJ, Rothera MP, Homer JJ (2008) Scientific and clinical aspects of the use of cidofovir in recurrent respiratory papillomatosis. Int J Pediatr Otorhinolaryngol 72(7):939–944PubMedCrossRefGoogle Scholar
  24. 24.
    Snoeck R, Wellens W, Desloovere C et al (1998) Treatment of severe laryngeal papillomatosis with intralesional injections of cidofovir [(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine]. J Med Virol 54(3):219–225PubMedCrossRefGoogle Scholar
  25. 25.
    Derkay CS, Volsky PG, Rosen CA, Pransky SM, McMurray JS et al (2013) Current use of intralesional cidofovir for recurrent respiratory papillomatosis. Laryngoscope 123(3):705–712PubMedCrossRefGoogle Scholar
  26. 26.
    Villa LL, Ault KA, Giuliano AR, Costa RLR, Petta CA et al (2006) Imunologic responses following administration of a vaccine targeting human papillomavirus types 6, 11, 16, and 18. Vaccine 24(27–28):5571–5583PubMedCrossRefGoogle Scholar
  27. 27.
    Garland SM, Smith JS (2010) Human papillomavirus vaccines: current status and future prospects. Drugs 70(9):1079–1098PubMedCrossRefGoogle Scholar
  28. 28.
    Elbasha EH, Dasbach EJ (2010) Impact of vaccinating boys and men against HPV in the United States. Vaccine 28(42):6858–6867PubMedCrossRefGoogle Scholar
  29. 29.
    Kim JJ (2011) Focus on research: weighing the benefits and costs of HPV vaccination of young men. N Engl J Med 364(5):393–395PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.ENT Department“Iuliu Haţieganu” University of Medicine and PharmacyCluj-NapocaRomania
  2. 2.ENT Department of the Emergency County HospitalCluj-NapocaRomania
  3. 3.Medical Informatics and Biostatistic Department“Iuliu Haţieganu” University of Medicine and PharmacyCluj-NapocaRomania

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