Elsevier

Journal of Infection

Volume 66, Issue 3, March 2013, Pages 207-217
Journal of Infection

Review
Risk factors for and prevention of human papillomaviruses (HPV), genital warts and cervical cancer

https://doi.org/10.1016/j.jinf.2012.10.024Get rights and content

Summary

Genital HPV infection is associated with development of cervical cancer, cervical neoplasia, anogenital warts, and other anogenital cancers. A number of reviews have primarily addressed the role of HPV infection in cervical carcinogenesis, and differences in human papillomavirus (HPV) subtypes found in cervical cancer cases by histology and geographical region. This review provides an informative summary of the broad body of literature on the burden of HPV, the risk factors for HPV infection, genital warts and cervical cancer, and preventive measures against these conditions in females. Studies have identified the main risk factors for genital HPV infection in females as follows: acquisition of new male partners; an increasing number of lifetime sexual partners both in females and their male partners; and having non-monogamous male partners. Cervical cancer screening and HPV vaccination are the primary measures currently recommended to prevent cervical cancer. There is also an ongoing debate and conflicting findings on whether male circumcision and condom use protect against HPV infection and subsequent development of HPV-related illnesses in females.

Section snippets

HPV infection

Papillomaviruses are double-stranded deoxyribonucleic acid (DNA) viruses that are small, non-enveloped and icosahedral with a diameter of 52–55 nm.1, 2 They are also epitheliotropic, which means that they generate productive infections merely within the stratified epithelia of the skin, oral cavity and anogenital tract. Infection of basal epithelial cells initiates the viral life cycle, which is linked to differentiation of the infected epithelial cells.3

Of more than 100 HPV types that have

Genital warts

Approximately 90% of genital warts – also known as condylomata acuminate – are caused by infection with HPV-6 and HPV-11.30, 37, 38, 39, 40 Genital warts are highly contagious with the majority of warts developing within 2–3 months of infection.21, 41 Winer et al.21 found the median duration between incident infection with HPV-6 or HPV-11 and development of genital warts to be 2.9 months among 18–20 year old females in the U.S. Furthermore, among females newly infected with HPV-6 and HPV-11,

Cervical cancer

For cervical cancer to develop, the following occur: infection with HPV; persistence of HPV infections; development of precancerous lesions in cervical cells that have been persistently infected with HPV; and invasion of cervical cells (cancer). It is common for HPV infections to clear, but less frequent for precancerous lesions to regress to normal cells.53

Cervical cancer ranks as the second most common cancer among both women of all ages and those aged 15–44 years worldwide. It was estimated

HPV vaccines

There are two vaccines currently available to prevent infection with HPV types responsible for most cervical cancer cases. The aim of prophylactic vaccination is to reduce incidence of anogenital cancers and precancerous lesions, with additional protective benefits against genital warts for those receiving the quadrivalent vaccine.69

In June 2006, the U.S. Food and Drug Administration (FDA) approved the prophylactic quadrivalent vaccine, Gardasil® (Merck, New Jersey, United States), for females

Summary

HPV has been associated with the development of cervical cancer in females, genital warts, and other anogenital cancers. It has also been linked to oropharyngeal, oral and laryngeal squamous cell carcinomas, and non-melanoma skin cancer. Although genital warts do not result in high morbidity and mortality, they are associated with significant medical costs and psychological distress to sufferers due to anxiety, discomfort, pain and embarrassment. The major risk factors for HPV infection are

Conflict of interest

The authors have no conflicts of interest.

References (109)

  • J.S. Smith et al.

    Cervical cancer and use of hormonal contraceptives: a systematic review

    Lancet

    (2003)
  • N. Muñoz et al.

    Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study

    Lancet

    (2002)
  • V. Cogliano et al.

    Carcinogenicity of combined oestrogen–progestagen contraceptives and menopausal treatment

    Lancet Oncol

    (2005)
  • V. Moreno et al.

    Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study

    Lancet

    (2002)
  • E.A. Joura 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 randomised clinical trials

    Lancet

    (2007)
  • K.A. Ault et al.

    A phase I study to evaluate a human papillomavirus (HPV) type 18 L1 VLP vaccine

    Vaccine

    (2004)
  • L.L. Villa et al.

    Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial

    Lancet Oncol

    (2005)
  • D.M. Harper et al.

    Sustained efficacy up to 4·5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial

    Lancet

    (2006)
  • J. Paavonen et al.

    Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial

    Lancet

    (2007)
  • T.C. Wright et al.

    Chapter 30: HPV vaccines and screening in the prevention of cervical cancer; conclusions from a 2006 workshop of international experts

    Vaccine

    (2006)
  • M. Stanley et al.

    Chapter 12: prophylactic HPV vaccines: underlying mechanisms

    Vaccine

    (2006)
  • M. Spitzer

    Cervical screening adjuncts: recent advances

    Am J Obstet Gynecol

    (1998)
  • G.P. Garnett et al.

    Chapter 21: modelling the impact of HPV vaccines on cervical cancer and screening programmes

    Vaccine

    (2006)
  • X. Castellsagué et al.

    HPV and circumcision: a biased, inaccurate and misleading meta-analysis

    J Infect

    (2007)
  • R.S. Van Howe

    Human papillomavirus and circumcision: a meta-analysis

    J Infect

    (2007)
  • M. Favre

    Structural polypeptides of rabbit, bovine, and human papillomaviruses

    J Virol

    (1975)
  • IARC monographs on the evaluation of carcinogenic risks to human

    (2007)
  • X. Castellsagué et al.

    HPV and cervical cancer in the world. 2007 report. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre)

    Vaccine

    (2007)
  • R.D. Burk et al.

    Sexual behavior and partner characteristics are the predominant risk factors for genital human papillomavirus infection in young women

    J Infect Dis

    (1996)
  • IARC monographs on the evaluation of carcinogenic risks to humans. Human papillomaviruses

    (1995)
  • N. Muñoz et al.

    Epidemiologic classification of human papillomavirus types associated with cervical cancer

    N Engl J Med

    (2003)
  • M.V. Jacobs et al.

    Group-specific differentiation between high- and low-risk human papillomavirus genotypes by general primer-mediated PCR and two cocktails of oligonucleotide probes

    J Clin Microbiol

    (1995)
  • N.W.J. Bulkmans et al.

    High-risk HPV type-specific clearance rates in cervical screening

    Br J Cancer

    (2007)
  • F.X. Bosch et al.

    Prevalence of human papillomavirus in cervical cancer: a worldwide perspective

    J Natl Cancer Inst

    (1995)
  • G.M. Clifford et al.

    Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis

    Br J Cancer

    (2003)
  • H. zur Hausen

    Human papillomaviruses and their possible role in squamous cell carcinomas

    Curr Top Microbiol Immunol

    (1977)
  • M. Boshart et al.

    A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer

    EMBO J

    (1984)
  • M. Durst et al.

    A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions

    Proc Natl Acad Sci U S A

    (1983)
  • J.M.M. Walboomers et al.

    Human papillomavirus is a necessary cause of invasive cervical cancer worldwide

    J Pathol

    (1999)
  • J.S. Smith et al.

    Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update

    Int J Cancer

    (2007)
  • R.L. Winer et al.

    Development and duration of human papillomavirus lesions, after initial infection

    J Infect Dis

    (2005)
  • F.X. Bosch et al.

    The epidemiology of human papillomavirus infection and cervical cancer

    Dis Markers

    (2007)
  • J.S. Smith et al.

    Chlamydia trachomatis and invasive cervical cancer: a pooled analysis of the IARC multicentric case-control study

    Int J Cancer

    (2004)
  • A.R. Kreimer et al.

    Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review

    Cancer Epidemiol Biomarkers Prev

    (2005)
  • U. Leiter et al.

    Epidemiology of melanoma and nonmelanoma skin cancer – the role of sunlight

    Adv Exp Med Biol

    (2008)
  • National Cancer Institute

    Skin cancer

    (2011)
  • H. Pfister

    Chapter 8: human papillomavirus and skin cancer

    J Natl Cancer Inst Monogr

    (2003)
  • S.K. Kjaer et al.

    High-risk human papillomavirus is sexually transmitted: evidence from a follow-up study of virgins starting sexual activity (intercourse)

    Cancer Epidemiol Biomarkers Prev

    (2001)
  • R.L. Winer et al.

    Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students

    Am J Epidemiol

    (2003)
  • D.R. Brown et al.

    A longitudinal study of genital human papillomavirus infection in a cohort of closely followed adolescent women

    J Infect Dis

    (2005)
  • Cited by (209)

    View all citing articles on Scopus
    View full text