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Understanding and learning from the success of prophylactic human papillomavirus vaccines

Nature Reviews Microbiology volume 10, pages 681692 (2012) | Download Citation


An estimated 5% of human cancers are caused by human papillomavirus (HPV) infections, and most of these cancers are of the cervix. Two prophylactic HPV vaccines that target the two most oncogenic virus types, HPV16 and HPV18, are now commercially available. In controlled clinical trials, the vaccines proved to be effective at preventing incident anogenital infection and the associated neoplastic disease that is induced by these virus types. Here, we highlight the specific aspects of HPV biology and vaccine composition that are likely to contribute to the efficacy of these vaccines, and we discuss how these particular features might or might not be relevant for the development of effective vaccines against other sexually transmitted viruses such as HIV and herpes simplex virus (HSV).

Key points

  • Human papillomaviruses (HPVs) are the aetiological agents of approximately 5% of human cancers, most notably those of the cervix, oropharynx, anus, vulva, vagina and penis.

  • In clinical efficacy trials, vaccines based on virus-like particles (VLPs) were highly effective as prophylactic vaccines, preventing infection and the hyperproliferative lesions that are caused at the cervix, anus, vulva, vagina and penis by the HPV types targeted by the vaccines.

  • Two HPV VLP-containing vaccines, Gardasil and Cervarix, are licensed in many countries for general distribution to adolescent girls and young women and, in some countries, to adolescent boys and young men.

  • The high-titre, durable antibody responses that are induced by the VLPs are believed to be the primary mediators of protection.

  • Unique aspects of the viral infectious process, including initial binding to the epithelial basement membrane and slow cell entry kinetics, might account for the exceptional susceptibility of HPV to inhibition by vaccine-induced antibodies.

  • The insights learned from the remarkable efficiency of prophylactic HPV vaccines could potentially be applied to the design of effective vaccines for preventing the spread of other sexually transmitted viruses, such as HIV and HSV. However, differences in basic virological characteristics might make it difficult to directly transfer this knowledge between viruses.

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The authors' research was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health.

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  1. Building 37, Room 4106, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

    • John T. Schiller
    •  & Douglas R. Lowy


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Competing interests

John T. Schiller and Douglas R. Lowy are inventors on US Government-owned patents that have been licensed to Merck and GlaxoSmithKine Biologicals, the two companies that market human papillomavirus vaccines.

Corresponding author

Correspondence to John T. Schiller.


Hyperproliferative diseases

Pathologies that are characterized by excessive cell growth.

Stratified squamous epithelium

Multilayered body surface tissue in which the cells undergo an ordered process of differentiation after they divide and lose their attachment to the basement membrane. The cells of the uppermost layers acquire a flattened appearance.

Benign epithelial hyperplasia

A focal abnormal proliferation of epithelial cells, with no invasion of surrounding tissues.


Having an affinity for mucosal epithelium.

Intraepithelial neoplasia

A histology term denoting a focus of abnormally proliferating cells within an epithelium. Also called dysplasia.


A substance that increases the immune response to a vaccine.

Sterilizing immunity

An immune response that prevents initial infection in addition to preventing the disease outcome.

Breakthrough infections

Infections that occur despite preventive measures.

Herd immunity

The protection of non-vaccinated individuals in a population as a result of the overall reduction in microbial prevalence and, thereby, transmission to individuals who remain susceptible to infection.

Immunobridging studies

Vaccine trials that measure immune response outcomes and can be used to extend vaccination recommendations to groups for which vaccine efficacy against the disease has not been formally demonstrated.


The transport of plasma-derived antibodies across an intact epithelium.

Fc receptor

A cell surface molecule that binds a constant-region (Fc) domain of an antibody.


The passive leakage of plasma components at a site where the barrier function of an epithelial tissue has been compromised.

Pap test

(Papanicolaou test). A test for the detection of cervical cancer and pre-cancerous lesions. The test involves the collection of superficial cervical epithelial cells, staining of these cells and microscopic detection of abnormal cells.

Central self-antigens

Components of the body (self) that are regularly exposed to the systemic immune system.


A change from having undetectable levels to having detectable levels of serum antibodies against a specific antigen.


Active transport of an infectious virion across an intact epithelium.


A complex set of plasma proteins that act together to inactivate extracellular microorganisms.

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