Skip to main content

Advertisement

SpringerLink
Log in

Epidemiology of Low-Risk Human Papillomavirus

  • Recurrent Respiratory Papilloma (L. Akst, Section Editor)
  • Published:
Current Otorhinolaryngology Reports Aims and scope Submit manuscript

Abstract

Infection with low-risk human papillomaviruses (HPVs), mostly type 6 and 11, in the upper respiratory tract causes recurrent respiratory papillomatosis (RRP). Despite a relatively low incidence rate, RRP imposes significant morbidity upon affected patients and an enormous financial burden on the healthcare system. RRP can be further categorized into juvenile-onset RRP and adult-onset RRP, depending on the onset age. They may associate with different risk factors and incidence rates. Here, we review the epidemiology of RRP caused by low-risk HPV infection and discuss the impact of HPV vaccination on the prevalence of low-risk HPVs that cause RRP.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses. Virology. 2004;324(1):17–27. doi:10.1016/j.virol.2004.03.033.

    Article  PubMed  Google Scholar 

  2. Munoz N, Castellsague X, de Gonzalez AB, Gissmann L. Chapter 1: HPV in the etiology of human cancer. Vaccine. 2006;24 Suppl 3:S3/1–10. doi:10.1016/j.vaccine.2006.05.115

  3. Lacey CJ, Lowndes CM, Shah KV. Chapter 4: burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine. 2006;24 Suppl 3:S3/35–41. doi: 10.1016/j.vaccine.2006.06.015

  4. Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, Stanley MA. The biology and life-cycle of human papillomaviruses. Vaccine. 2012;30(Suppl 5):F55–70. doi:10.1016/j.vaccine.2012.06.083.

    Article  CAS  PubMed  Google Scholar 

  5. Munger K, Scheffner M, Huibregtse JM, Howley PM. Interactions of HPV E6 and E7 oncoproteins with tumour suppressor gene products. Cancer Surv. 1992;12:197–217.

    CAS  PubMed  Google Scholar 

  6. Klingelhutz AJ, Roman A. Cellular transformation by human papillomaviruses: lessons learned by comparing high- and low-risk viruses. Virology. 2012;424(2):77–98. doi:10.1016/j.virol.2011.12.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Best SR, Niparko KJ, Pai SI. Biology of human papillomavirus infection and immune therapy for HPV-related head and neck cancers. Otolaryngol Clin North Am. 2012;45(4):807–22. doi:10.1016/j.otc.2012.04.005.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Reeves WC, Ruparelia SS, Swanson KI, Derkay CS, Marcus A, Unger ER. National registry for juvenile-onset recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg. 2003;129(9):976–82. doi:10.1001/archotol.129.9.976.

    Article  PubMed  Google Scholar 

  9. Derkay CS, Darrow DH. Recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol. 2006;115(1):1–11.

    Article  PubMed  Google Scholar 

  10. Cohn AM, Kos JT 2nd, Taber LH, Adam E. Recurring laryngeal papillopa. Am J Otolaryngol. 1981;2(2):129–32.

    Article  CAS  PubMed  Google Scholar 

  11. Omland T, Akre H, Vardal M, Brondbo K. Epidemiological aspects of recurrent respiratory papillomatosis: a population-based study. Laryngoscope. 2012;122(7):1595–9. doi:10.1002/lary.23327.

    Article  PubMed  Google Scholar 

  12. Armstrong LR, Derkay CS, Reeves WC. Initial results from the national registry for juvenile-onset recurrent respiratory papillomatosis. RRP Task Force. Arch Otolaryngol Head Neck Surg. 1999;125(7):743–8.

    Article  CAS  PubMed  Google Scholar 

  13. Omland T, Akre H, Lie KA, Jebsen P, Sandvik L, Brondbo K. Risk factors for aggressive recurrent respiratory papillomatosis in adults and juveniles. PLoS ONE. 2014;9(11):e113584. doi:10.1371/journal.pone.0113584.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Derkay CS. Task force on recurrent respiratory papillomas. A preliminary report. Arch Otolaryngol Head Neck Surg. 1995;121(12):1386–91.

    Article  CAS  PubMed  Google Scholar 

  15. Klozar J, Taudy M, Betka J, Kana R. Laryngeal papilloma–precancerous condition? Acta Otolaryngol Suppl. 1997;527:100–2.

    Article  CAS  PubMed  Google Scholar 

  16. Karatayli-Ozgursoy S, Bishop JA, Hillel A, Akst L, Best SR. Risk factors for dysplasia in recurrent respiratory papillomatosis in an adult and pediatric population. Ann Otol Rhinol Laryngol. 2015;. doi:10.1177/0003489415608196.

    Google Scholar 

  17. Schraff S, Derkay CS, Burke B, Lawson L. American Society of Pediatric Otolaryngology members’ experience with recurrent respiratory papillomatosis and the use of adjuvant therapy. Arch Otolaryngol Head Neck Surg. 2004;130(9):1039–42. doi:10.1001/archotol.130.9.1039.

    Article  PubMed  Google Scholar 

  18. Venkatesan NN, Pine HS, Underbrink MP. Recurrent respiratory papillomatosis. Otolaryngol Clin North Am. 2012;45(3):671–94, viii–ix. doi:10.1016/j.otc.2012.03.006.

  19. Lindeberg H, Elbrond O. Laryngeal papillomas: the epidemiology in a Danish subpopulation 1965-1984. Clin Otolaryngol Allied Sci. 1990;15(2):125–31.

    Article  CAS  PubMed  Google Scholar 

  20. Robb PK Jr, Weinberger PM, Perakis H, Li A, Klein AM, Johns MM 3rd, Adkins LK, Postma GN. Association of asthma with clinically aggressive recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg. 2011;137(4):368–72. doi:10.1001/archoto.2011.44.

    Article  PubMed  Google Scholar 

  21. • Ruiz R, Achlatis S, Verma A, Born H, Kapadia F, Fang Y, Pitman M, Sulica L, Branski RC, Amin MR. Risk factors for adult-onset recurrent respiratory papillomatosis. Laryngoscope. 2014;124(10):2338–44. doi: 10.1002/lary.24730. This prospective age and sex matched case control study evaluated the risk factors for AORRP and identified increased number of lifetime sexual partners but not lifetime number of oral sex partners as the risk factor for AORRP.

  22. • San Giorgi M, van den Heuvel ER, Tjon Pian Gi RE, Brunings JW, Chirila M, Friedrich G, Golusinski W, Graupp M, Horcasitas Pous RA, Ilmarinen T, Jackowska J, Koelmel JC, Ferran Vila F, Weichbold V, Wierzbicka M, Dikkers FG. Age of onset of Recurrent Respiratory Papillomatosis: a distribution analysis. Clin Otolaryngol. 2015. doi: 10.1111/coa.12565. This is the first study to analyze actual age onset distribution among JORRP and AORRP patients. It is a cross-sectional European multicenter study that demonstrated three peaks of RRP around 7, 35, 64 years of age.

  23. Castle PE, Schiffman M, Herrero R, Hildesheim A, Rodriguez AC, Bratti MC, Sherman ME, Wacholder S, Tarone R, Burk RD. A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica. J Infect Dis. 2005;191(11):1808–16. doi:10.1086/428779.

    Article  PubMed  Google Scholar 

  24. Garcia-Pineres AJ, Hildesheim A, Herrero R, Trivett M, Williams M, Atmetlla I, Ramirez M, Villegas M, Schiffman M, Rodriguez AC, Burk RD, Hildesheim M, Freer E, Bonilla J, Bratti C, Berzofsky JA, Pinto LA. Persistent human papillomavirus infection is associated with a generalized decrease in immune responsiveness in older women. Cancer Res. 2006;66(22):11070–6. doi:10.1158/0008-5472.CAN-06-2034.

    Article  CAS  PubMed  Google Scholar 

  25. Kashima HK, Shah F, Lyles A, Glackin R, Muhammad N, Turner L, Van Zandt S, Whitt S, Shah K. A comparison of risk factors in juvenile-onset and adult-onset recurrent respiratory papillomatosis. Laryngoscope. 1992;102(1):9–13. doi:10.1288/00005537-199201000-00002.

    Article  CAS  PubMed  Google Scholar 

  26. • Born H, Ruiz R, Verma A, Taliercio S, Achlatis S, Pitman M, Gandonu S, Bing R, Amin MR, Branski RC. Concurrent oral human papilloma virus infection in patients with recurrent respiratory papillomatosis: a preliminary study. Laryngoscope. 2014;124(12):2785–90. doi: 10.1002/lary.24850. This is the first study that determined oral HPV colonization in AORRP patients and their long-term partners. A significantly higher rate of HPV oral colonization was found in AORRP and their partners. It provided preliminary information relevant for AORRP patient counseling.

  27. Sanders AE, Slade GD, Patton LL. National prevalence of oral HPV infection and related risk factors in the U.S. adult population. Oral Dis. 2012;18(5):430–41. doi:10.1111/j.1601-0825.2011.01892.x.

    Article  CAS  PubMed  Google Scholar 

  28. Rintala M, Grenman S, Puranen M, Syrjanen S. Natural history of oral papillomavirus infections in spouses: a prospective Finnish HPV Family Study. J Clin Virol. 2006;35(1):89–94. doi:10.1016/j.jcv.2005.05.012.

    Article  PubMed  Google Scholar 

  29. Rihkanen H, Peltomaa J, Syrjanen S. Prevalence of human papillomavirus (HPV) DNA in vocal cords without laryngeal papillomas. Acta Otolaryngol. 1994;114(3):348–51.

    Article  CAS  PubMed  Google Scholar 

  30. Park H, Lee SW, Lee IH, Ryu HM, Cho AR, Kang YS, Hong SR, Kim SS, Seong SJ, Shin SM, Kim TJ. Rate of vertical transmission of human papillomavirus from mothers to infants: relationship between infection rate and mode of delivery. Virol J. 2012;9:80. doi:10.1186/1743-422X-9-80.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Lai YM, Yang FP, Pao CC. Human papillomavirus deoxyribonucleic acid and ribonucleic acid in seminal plasma and sperm cells. Fertil Steril. 1996;65(5):1026–30.

    CAS  PubMed  Google Scholar 

  32. Rombaldi RL, Serafini EP, Mandelli J, Zimmermann E, Losquiavo KP. Transplacental transmission of human papillomavirus. Virol J. 2008;5:106. doi:10.1186/1743-422X-5-106.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Silverberg MJ, Thorsen P, Lindeberg H, Grant LA, Shah KV. Condyloma in pregnancy is strongly predictive of juvenile-onset recurrent respiratory papillomatosis. Obstet Gynecol. 2003;101(4):645–52.

    PubMed  Google Scholar 

  34. Shah KV, Stern WF, Shah FK, Bishai D, Kashima HK. Risk factors for juvenile onset recurrent respiratory papillomatosis. Pediatr Infect Dis J. 1998;17(5):372–6.

    Article  CAS  PubMed  Google Scholar 

  35. Chatzistamatiou K, Sotiriadis A, Agorastos T. Effect of mode of delivery on vertical human papillomavirus transmission—a meta-analysis. J Obstet Gynaecol. 2015;. doi:10.3109/01443615.2015.1030606.

    Google Scholar 

  36. Winckworth LC, Nichol R. Question 2: do caesarean sections reduce the maternal-fetal transmission rate of human papillomavirus infection? Arch Dis Child. 2010;95(1):70–3. doi:10.1136/adc.2009.171777.

    Article  PubMed  Google Scholar 

  37. Mammas IN, Sourvinos G, Giamarelou P, Michael C, Spandidos DA. Human papillomavirus in the oral cavity of children and mode of delivery: a retrospective study. Int J STD AIDS. 2012;23(3):185–8. doi:10.1258/ijsa.2009.009483.

    Article  CAS  PubMed  Google Scholar 

  38. Shi R, Devarakonda S, Liu L, Taylor H, Mills G. Factors associated with genital human papillomavirus infection among adult females in the United States, NHANES 2007-2010. BMC Res Notes. 2014;7:544. doi:10.1186/1756-0500-7-544.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Stern Y, Felipovich A, Cotton RT, Segal K. Immunocompetency in children with recurrent respiratory papillomatosis: prospective study. Ann Otol Rhinol Laryngol. 2007;116(3):169–71.

    Article  PubMed  Google Scholar 

  40. • Lucs AV, DeVoti JA, Hatam L, Afzal A, Abramson AL, Steinberg BM, Bonagura VR. Immune dysregulation in patients persistently infected with human papillomaviruses 6 and 11. J Clin Med. 2015;4(3):375–88. doi: 10.3390/jcm4030375. This review described innate and adaptive immune dysfunctions that fail to mount effective antiviral responses in RRP patients.

  41. Hatam LJ, Devoti JA, Rosenthal DW, Lam F, Abramson AL, Steinberg BM, Bonagura VR. Immune suppression in premalignant respiratory papillomas: enriched functional CD4+ Foxp3+ regulatory T cells and PD-1/PD-L1/L2 expression. Clin Cancer Res. 2012;18(7):1925–35. doi:10.1158/1078-0432.CCR-11-2941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Rosenthal DW, DeVoti JA, Steinberg BM, Abramson AL, Bonagura VR. T(H)2-like chemokine patterns correlate with disease severity in patients with recurrent respiratory papillomatosis. Mol Med. 2012;18:1338–45. doi:10.2119/molmed.2012.00284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Bonagura VR, Hatam L, DeVoti J, Zeng F, Steinberg BM. Recurrent respiratory papillomatosis: altered CD8(+) T-cell subsets and T(H)1/T(H)2 cytokine imbalance. Clin Immunol. 1999;93(3):302–11. doi:10.1006/clim.1999.4784.

    Article  CAS  PubMed  Google Scholar 

  44. Bonagura VR, Du Z, Ashouri E, Luo L, Hatam LJ, DeVoti JA, Rosenthal DW, Steinberg BM, Abramson AL, Gjertson DW, Reed EF, Rajalingam R. Activating killer cell immunoglobulin-like receptors 3DS1 and 2DS1 protect against developing the severe form of recurrent respiratory papillomatosis. Hum Immunol. 2010;71(2):212–9. doi:10.1016/j.humimm.2009.10.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. DeVoti J, Hatam L, Lucs A, Afzal A, Abramson A, Steinberg B, Bonagura V. Decreased Langerhans cell responses to IL-36gamma: altered innate immunity in patients with recurrent respiratory papillomatosis. Mol Med. 2014;20:372–80. doi:10.2119/molmed.2014.00098.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Bonagura VR, Vambutas A, DeVoti JA, Rosenthal DW, Steinberg BM, Abramson AL, Shikowitz MJ, Gjertson DW, Reed EF. HLA alleles, IFN-gamma responses to HPV-11 E6, and disease severity in patients with recurrent respiratory papillomatosis. Hum Immunol. 2004;65(8):773–82. doi:10.1016/j.humimm.2004.05.014.

    Article  CAS  PubMed  Google Scholar 

  47. Gregoire L, Reidy PM, Rabah R, Lancaster WD. HLA-DQ alleles in white and African American patients with juvenile-onset recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg. 2003;129(11):1221–4. doi:10.1001/archotol.129.11.1221.

    Article  PubMed  Google Scholar 

  48. Campisi P, Hawkes M, Simpson K, Canadian Juvenile Onset Recurrent Respiratory Papillomatosis Working G. The epidemiology of juvenile onset recurrent respiratory papillomatosis derived from a population level national database. Laryngoscope. 2010;120(6):1233–45. doi:10.1002/lary.20901.

    PubMed  Google Scholar 

  49. Silverberg MJ, Thorsen P, Lindeberg H, Ahdieh-Grant L, Shah KV. Clinical course of recurrent respiratory papillomatosis in Danish children. Arch Otolaryngol Head Neck Surg. 2004;130(6):711–6. doi:10.1001/archotol.130.6.711.

    Article  PubMed  Google Scholar 

  50. Wiatrak BJ, Wiatrak DW, Broker TR, Lewis L. Recurrent respiratory papillomatosis: a longitudinal study comparing severity associated with human papilloma viral types 6 and 11 and other risk factors in a large pediatric population. Laryngoscope. 2004;114(11 Pt 2 Suppl 104):1–23. doi: 10.1097/01.mlg.000148224.83491.0f.

  51. Leung R, Hawkes M, Campisi P. Severity of juvenile onset recurrent respiratory papillomatosis is not associated with socioeconomic status in a setting of universal health care. Int J Pediatr Otorhinolaryngol. 2007;71(6):965–72. doi:10.1016/j.ijporl.2007.03.009.

    Article  CAS  PubMed  Google Scholar 

  52. Armstrong LR, Preston EJ, Reichert M, Phillips DL, Nisenbaum R, Todd NW, Jacobs IN, Inglis AF, Manning SC, Reeves WC. Incidence and prevalence of recurrent respiratory papillomatosis among children in Atlanta and Seattle. Clin Infect Dis. 2000;31(1):107–9. doi:10.1086/313914.

    Article  CAS  PubMed  Google Scholar 

  53. •• Marsico M, Mehta V, Chastek B, Liaw KL, Derkay C. Estimating the incidence and prevalence of juvenile-onset recurrent respiratory papillomatosis in publicly and privately insured claims databases in the United States. Sex Transm Dis. 2014;41(5):300–5. doi: 10.1097/OLQ.0000000000000115. This study used medical claims based databases to estimate the incidence and prevalence of JORRP among publicly and privately insured children in the United States. Although it suggested the increased disease burden in lower socioeconomic status cohort, the association between the socioeconomic status and the disease is not statistically tested.

  54. Bomholt A. Laryngeal papillomas with adult onset. An epidemiological study from the Copenhagen region. Acta Otolaryngol. 1988;106(1–2):140–4.

    Article  CAS  PubMed  Google Scholar 

  55. Bomholt A. Juvenile laryngeal papillomatosis. An epidemiological study from the Copenhagen region. Acta Otolaryngol. 1988;105(3–4):367–71.

    Article  CAS  PubMed  Google Scholar 

  56. Novakovic D, Cheng AT, Cope DH, Brotherton JM. Estimating the prevalence of and treatment patterns for juvenile onset recurrent respiratory papillomatosis in Australia pre-vaccination: a pilot study. Sex Health. 2010;7(3):253–61. doi:10.1071/SH09142.

    Article  PubMed  Google Scholar 

  57. Chesson HW, Ekwueme DU, Saraiya M, Watson M, Lowy DR, Markowitz LE. Estimates of the annual direct medical costs of the prevention and treatment of disease associated with human papillomavirus in the United States. Vaccine. 2012;30(42):6016–9. doi:10.1016/j.vaccine.2012.07.056.

    Article  PubMed  Google Scholar 

  58. Petrosky E, Bocchini JA Jr, Hariri S, Chesson H, Curtis CR, Saraiya M, Unger ER, Markowitz LE, Centers for Disease C, Prevention. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2015;64(11):300–4.

    PubMed  Google Scholar 

  59. Markowitz LE, Dunne EF, Saraiya M, Chesson HW, Curtis CR, Gee J, Bocchini JA, Jr., Unger ER, Centers for Disease C, Prevention. Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2014;63(RR-05):1–30.

  60. Stokley S, Jeyarajah J, Yankey D, Cano M, Gee J, Roark J, Curtis RC, Markowitz L, Immunization Services Division NCfI, Respiratory Diseases CDC, Centers for Disease C, Prevention. Human papillomavirus vaccination coverage among adolescents, 2007-2013, and postlicensure vaccine safety monitoring, 2006-2014–United States. MMWR Morb Mortal Wkly Rep. 2014;63(29):620–4.

    PubMed  Google Scholar 

  61. Reagan-Steiner S, Yankey D, Jeyarajah J, Elam-Evans LD, Singleton JA, Curtis CR, MacNeil J, Markowitz LE, Stokley S. National, regional, state, and selected local area vaccination coverage among adolescents aged 13–17 years-United States, 2014. MMWR Morb Mortal Wkly Rep. 2015;64(29):784–92.

    Article  PubMed  Google Scholar 

  62. Markowitz LE, Hariri S, Lin C, Dunne EF, Steinau M, McQuillan G, Unger ER. Reduction in human papillomavirus (HPV) prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003–2010. J Infect Dis. 2013;208(3):385–93. doi:10.1093/infdis/jit192.

    Article  CAS  PubMed  Google Scholar 

  63. •• Dunne EF, Naleway A, Smith N, Crane B, Weinmann S, Braxton J, Steinau M, Unger ER, Markowitz LE. Reduction in human papillomavirus vaccine type prevalence among young women screened for cervical cancer in an Integrated US Healthcare Delivery System in 2007 and 2012–2013. J Infect Dis. 2015;212(12):1970–5. doi: 10.1093/infdis/jiv342. This study assessed HPV prevalence in women age 20–29 years screened for cervical cancer in pre-vaccine and post-vaccine periods in the northwest United States. Their results showed reductions of vaccine type HPV prevalence due to the impact of quadrivalent HPV vaccine. It demonstrated that HPV vaccine initiation before 19 years of age was associated with decreased vaccine type HPV prevalence in post-vaccine periods.

  64. •• Perkins RB, Legler A, Hanchate A. Trends in male and female genital warts among adolescents in a Safety-Net Health Care System 2004–2013: correlation with introduction of female and male human papillomavirus vaccination. Sex Transm Dis. 2015;42(12):665–8. doi: 10.1097/OLQ.0000000000000369. This study specifically described the rates of genital warts among low-income and minority adolescent populations during 3 periods between 2004 and 2013. It showed a decreasing trend of female and male genital warts rates after introduction of female vaccination and a further decline after introduction of male vaccination.

Download references

Author information

Authors and Affiliations

  1. Departments of Otolaryngology, and Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA

    Jia Wang & Michael P. Underbrink

Authors
  1. Jia Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael P. Underbrink
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael P. Underbrink.

Additional information

This article is part of the Topical Collection on Recurrent Respiratory Papilloma.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Underbrink, M.P. Epidemiology of Low-Risk Human Papillomavirus. Curr Otorhinolaryngol Rep 4, 99–106 (2016). https://doi.org/10.1007/s40136-016-0112-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40136-016-0112-6

Keywords

Search

Navigation