Skip to main content

Advertisement

Log in

Natural History of Human Papilloma Virus Infection of the Cervix

  • Management of HPV and Associated Cervical Lesions (L Denny, Section Editor)
  • Published:
Current Obstetrics and Gynecology Reports Aims and scope Submit manuscript

Abstract

Persistent HPV infection with an oncogenic strain of high-risk HPV is a necessary risk factor for the development of invasive cervical cancer. The improved understanding of the cytopathic effects of HPV led to the development of novel diagnostic and preventative tools. HPV manages to evade the immune response of the host. Oncogenic HPV infection does not progress to cancer in all infected individuals and certain variables make individuals more susceptible to the development of pre-malignant and malignant disease. The alpha HPV types are divided into high- and low-risk types according to their ability to cause malignant disease. HPV is mostly transmitted by mucosal contact and infects basal keratinocytes, most likely at a site of micro-trauma that exposes the basal layer to virus. The ability of low-risk HPV to disrupt cell proliferation is limited. In high-risk HPV infections, E6 and E7 are expressed early and strongly leading to accumulation of genetic changes that progress to cancer. The specific HPV type is the strongest factor associated with persistence and oncogenic potential. The concept of latency and reactivation may explain the re-emergence of HPV DNA detection many years after exposure. After a period of latency, reactivation of detectable HPV may follow immune suppression or hormonal changes.

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.

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. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.

    Article  PubMed  Google Scholar 

  2. Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, et al. Global burden of human papillomavirus and related diseases. Vaccine. 2012;30 Suppl 5:F12–23.

    Article  PubMed  Google Scholar 

  3. Bosch FX, de Sanjose S. Chapter 1: Human papillomavirus and cervical cancer—burden and assessment of causality. J Natl Cancer Inst Monogr. 2003;31:3–13.

    Article  PubMed  Google Scholar 

  4. Woolhouse M, Scott F, Hudson Z, Howey R, Chase-Topping M. Human viruses: discovery and emergence. Philos Trans R Soc Lond B Biol Sci. 2012;367(1604):2864–71.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Fornaciari G, Zavaglia K, Giusti L, Vultaggio C, Ciranni R. Human papillomavirus in a 16th century mummy. Lancet. 2003;362(9390):1160.

    Article  PubMed  Google Scholar 

  6. Bosch FX, Burchell AN, Schiffman M, Giuliano AR, de Sanjose S, Bruni L, et al. Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia. Vaccine. 2008;26 Suppl 10:K1–K16. Comprehensive review of the topic.

    Article  PubMed  Google Scholar 

  7. Cubie HA. Diseases associated with human papillomavirus infection. Virology. 2013;445(1–2):21–34. Good overview of HPV associated disease.

    Article  CAS  PubMed  Google Scholar 

  8. Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, et al. The biology and life-cycle of human papillomaviruses. Vaccine. 2012;30 Suppl 5:F55–70.

    Article  CAS  PubMed  Google Scholar 

  9. Bravo IG, de Sanjose S, Gottschling M. The clinical importance of understanding the evolution of papillomaviruses. Trends Microbiol. 2010;18(10):432–8.

    Article  CAS  PubMed  Google Scholar 

  10. Quint KD, Genders RE, de Koning MN, Borgogna C, Gariglio M, Bouwes Bavinck JN, et al. Human Beta-papillomavirus infection and keratinocyte carcinomas. J Pathol. 2015;235(2):342–54.

    Article  CAS  PubMed  Google Scholar 

  11. Seedat RY, Thukane M, Jansen AC, Rossouw I, Goedhals D, Burt FJ. HPV types causing juvenile recurrent laryngeal papillomatosis in South Africa. Int J Pediatr Otorhinolaryngol. 2010;74(3):255–9.

    Article  CAS  PubMed  Google Scholar 

  12. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–9.

    Article  CAS  PubMed  Google Scholar 

  13. Zielinski GD, Snijders PJ, Rozendaal L, Daalmeijer NF, Risse EK, Voorhorst FJ, et al. The presence of high-risk HPV combined with specific p53 and p16INK4a expression patterns points to high-risk HPV as the main causative agent for adenocarcinoma in situ and adenocarcinoma of the cervix. J Pathol. 2003;201(4):535–43.

    Article  CAS  PubMed  Google Scholar 

  14. Rozendaal L, Walboomers JM, van der Linden JC, Voorhorst FJ, Kenemans P, Helmerhorst TJ, et al. PCR-based high-risk HPV test in cervical cancer screening gives objective risk assessment of women with cytomorphologically normal cervical smears. Int J Cancer J Int Cancer. 1996;68(6):766–9.

    Article  CAS  Google Scholar 

  15. World Health Oorganization International Agency For Research On Cancer. IARC monographs on the evaluation of carcinogenic risks to humans, volume 90, human papillomaviruses. 2006.

  16. Parkin DM, Bray F. Chapter 2: the burden of HPV-related cancers. Vaccine. 2006;24 Suppl 3:S3/11–25.

    Google Scholar 

  17. Herfs M, Yamamoto Y, Laury A, Wang X, Nucci MR, McLaughlin-Drubin ME, et al. A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Natl Acad Sci U S A. 2012;109(26):10516–21. Novel concept of uniqueness of cervical transformation zone.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Wang X, Ouyang H, Yamamoto Y, Kumar PA, Wei TS, Dagher R, et al. Residual embryonic cells as precursors of a Barrett’s-like metaplasia. Cell. 2011;145(7):1023–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Yang EJ, Quick MC, Hanamornroongruang S, Lai K, Doyle LA, McKeon FD, et al. Microanatomy of the cervical and anorectal squamocolumnar junctions: a proposed model for anatomical differences in HPV-related cancer risk. Mod Pathol : Off J U S Can Acad Pathol Inc. 2015;28(7):994–1000.

    Article  CAS  Google Scholar 

  20. Kurman RJ, Schiffman MH, Lancaster WD, Reid R, Jenson AB, Temple GF, et al. Analysis of individual human papillomavirus types in cervical neoplasia: a possible role for type 18 in rapid progression. Am J Obstet Gynecol. 1988;159(2):293–6.

    Article  CAS  PubMed  Google Scholar 

  21. Woodman CB, Collins S, Rollason TP, Winter H, Bailey A, Yates M, et al. Human papillomavirus type 18 and rapidly progressing cervical intraepithelial neoplasia. Lancet. 2003;361(9351):40–3.

    Article  PubMed  Google Scholar 

  22. de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048–56.

    Article  PubMed  Google Scholar 

  23. Burchell AN, Winer RL, de Sanjose S, Franco EL. Chapter 6: Epidemiology and transmission dynamics of genital HPV infection. Vaccine. 2006;24 Suppl 3:S3/52–61.

    Google Scholar 

  24. Stanley MA. Epithelial cell responses to infection with human papillomavirus. Clin Microbiol Rev. 2012;25(2):215–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Schiller JT, Day PM, Kines RC. Current understanding of the mechanism of HPV infection. Gynecol Oncol. 2010;118(1 Suppl):S12–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Hickman ES, Moroni MC, Helin K. The role of p53 and pRB in apoptosis and cancer. Curr Opin genet Dev. 2002;12(1):60–6.

    Article  CAS  PubMed  Google Scholar 

  27. Woodman CB, Collins S, Winter H, Bailey A, Ellis J, Prior P, et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet. 2001;357(9271):1831–6.

    Article  CAS  PubMed  Google Scholar 

  28. Appleby P, Beral V, Berrington de Gonzalez A, Colin D, Franceschi S, Goodill A, et al. Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J cancer J Int cancer. 2006;118(6):1481–95.

    Article  CAS  Google Scholar 

  29. Smith JS, Green J, Berrington de Gonzalez A, Appleby P, Peto J, Plummer M, et al. Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet. 2003;361(9364):1159–67.

    Article  PubMed  Google Scholar 

  30. Monnier-Benoit S, Mauny F, Riethmuller D, Guerrini JS, Capilna M, Felix S, et al. Immunohistochemical analysis of CD4+ and CD8+ T-cell subsets in high risk human papillomavirus-associated pre-malignant and malignant lesions of the uterine cervix. Gynecol Oncol. 2006;102(1):22–31.

    Article  PubMed  Google Scholar 

  31. Stanley M. Immune responses to human papillomavirus. Vaccine. 2006;24 Suppl 1:S16–22.

    Article  PubMed  Google Scholar 

  32. Castle PE, Schiffman M, Herrero R, Hildesheim A, Rodriguez AC, Bratti MC, et al. 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.

    Article  PubMed  Google Scholar 

  33. Koshiol JE, Schroeder JC, Jamieson DJ, Marshall SW, Duerr A, Heilig CM, et al. Time to clearance of human papillomavirus infection by type and human immunodeficiency virus serostatus. Int J Cancer J Int Cancer. 2006;119(7):1623–9.

    Article  CAS  Google Scholar 

  34. Schiffman M, Herrero R, Desalle R, Hildesheim A, Wacholder S, Rodriguez AC, et al. The carcinogenicity of human papillomavirus types reflects viral evolution. Virology. 2005;337(1):76–84.

    Article  CAS  PubMed  Google Scholar 

  35. Barrow-Laing L, Chen W, Roman A. Low- and high-risk human papillomavirus E7 proteins regulate p130 differently. Virology. 2010;400(2):233–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Stanley M. Immunobiology of HPV and HPV vaccines. Gynecol Oncol. 2008;109(2 Suppl):S15–21.

    Article  CAS  PubMed  Google Scholar 

  37. Kanodia S, Fahey LM, Kast WM. Mechanisms used by human papillomaviruses to escape the host immune response. Curr Cancer Drug Targets. 2007;7(1):79–89.

    Article  CAS  PubMed  Google Scholar 

  38. Maglennon GA, McIntosh P, Doorbar J. Persistence of viral DNA in the epithelial basal layer suggests a model for papillomavirus latency following immune regression. Virology. 2011;414(2):153–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Heard I, Tassie JM, Schmitz V, Mandelbrot L, Kazatchkine MD, Orth G. Increased risk of cervical disease among human immunodeficiency virus-infected women with severe immunosuppression and high human papillomavirus load(1). Obstet Gynecol. 2000;96(3):403–9.

    Article  CAS  PubMed  Google Scholar 

  40. Palefsky JM, Minkoff H, Kalish LA, Levine A, Sacks HS, Garcia P, et al. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst. 1999;91(3):226–36.

    Article  CAS  PubMed  Google Scholar 

  41. Zeier MD, Botha MH, van der Merwe FH, Eshun-Wilson I, van Schalkwyk M, la Grange M, et al. Progression and persistence of low-grade cervical squamous intraepithelial lesions in women living with human immunodeficiency virus. J Lower Genit tract Dis. 2012;16(3):243–50.

    Article  Google Scholar 

  42. Moodley M, Mould S. Invasive cervical cancer and human immunodeficiency virus (HIV) infection in KwaZulu-Natal, South Africa. J obstet Gynaecol : J Inst Obstet Gynaecol. 2005;25(7):706–10.

    Article  CAS  Google Scholar 

  43. Averbach SH, Gravitt PE, Nowak RG, Celentano DD, Dunbar MS, Morrison CS, et al. The association between cervical human papillomavirus infection and HIV acquisition among women in Zimbabwe. AIDS. 2010;24(7):1035–42.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Auvert B, Lissouba P, Cutler E, Zarca K, Puren A, Taljaard D. Association of oncogenic and nononcogenic human papillomavirus with HIV incidence. J Acquir Immune Defic Syndr. 2010;53(1):111–6.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Veldhuijzen NJ, Vyankandondera J, van de Wijgert JH. HIV acquisition is associated with prior high-risk human papillomavirus infection among high-risk women in Rwanda. AIDS. 2010;24(14):2289–92.

    Article  PubMed  Google Scholar 

  46. van der Loeff MF, Nyitray AG, Giuliano AR. HPV vaccination to prevent HIV infection: time for randomized controlled trials. Sex Transm Dis. 2011;38(7):640–3.

    Article  PubMed  Google Scholar 

  47. Denny LA, Franceschi S, de Sanjose S, Heard I, Moscicki AB, Palefsky J. Human papillomavirus, human immunodeficiency virus and immunosuppression. Vaccine. 2012;30 Suppl 5:F168–74. Good overview of HPV disease in immunocompromised individuals.

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Matthys Hendrik Botha declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Matthys Hendrik Botha.

Additional information

This article is part of the Topical Collection on Management of HPV and Associated Cervical Lesions

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Botha, M.H. Natural History of Human Papilloma Virus Infection of the Cervix. Curr Obstet Gynecol Rep 4, 189–194 (2015). https://doi.org/10.1007/s13669-015-0135-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13669-015-0135-x

Keywords

Navigation