Human Papillomavirus (HPV)

Human papillomavirus (HPV) is a small, non-enveloped deoxyribonucleic acid (DNA) virus that infects skin or mucosal cells. The circular, double-stranded viral genome is approximately 8-kb in length. The genome encodes for 6 early proteins responsible for virus replication and 2 late proteins, L1 and L2, which are the viral structural proteins. At least 13 of more than 100 known HPV genotypes can cause cancer of the cervix and are associated with other anogenital cancers and cancers of the head and neck. The two most common "high-risk" genotypes (HPV 16 and 18) cause approximately 70% of all cervical cancers. HPV was estimated to cause almost half a million cases and 250,000 deaths from cervical cancer in 2002, of which about 80% occurred in developing countries. Two "low-risk" genotypes (HPV 6 and 11) cause genital warts, a common benign condition of the external genitalia that causes significant morbidity. HPV is highly transmissible, with peak incidence soon after the onset of sexual activity, and most persons acquire infection at some time in their lives.

HPV Vaccines

Two prophylactic HPV vaccines have been available since 2006. Both vaccines are prepared from virus-like particles (VLPs) produced by recombinant technology. Purified L1 protein self-assembles to form empty shells that resemble HPV VLPs. These vaccines do not contain viral genetic material or live biological product, so they cannot multiply and are not infectious. These two vaccines are:

• A bivalent vaccine comprised of HPV types 16 and 18 protein expressed and purified from insect cells infected with a recombinant baculovirus. This vaccine is formulated with a novel adjuvant, AS04, which contains aluminium hydroxide and monophosphoryl lipid A (MPL); and
• A tetravalent vaccine comprised of HPV types 6, 11, 16 and 18 expressed and purified from yeast cells containing the specific L1 expression plasmids.

The VLPs are adsorbed to an amorphous aluminium hydroxyphosphate sulfate adjuvant. Both vaccines induced high levels of serum antibodies against all vaccine-related types in more than 99% of females aged 9–45 years (quadrivalent vaccine) or 10–55 years (bivalent vaccine). Neutralizing antibodies to HPV are thought to be important in protection. However, so far, a serologic correlate of protection has not been identified, and the minimum antibody level required for clinical protection is unknown.

Written Standards

In 2006 WHO held a series of consultations to develop guidelines for prophylactic human papillomavirus (HPV) vaccines. The document provides background and guidance to national regulatory authorities and vaccine manufacturers on the production, quality control and evaluation of the safety and efficacy of recombinant HPV virus-like particle (VLP) vaccines.

Recommendations to assure the quality, safety and efficacy of recombinant human papillomavirus virus-like particle vaccines, Technical Report Series, No. 999, Annex 4. Replacement of Annex 1 of WHO Technical Report Series, No. 962.

Reference materials

Anti-HPV type 16 serum (1st International Standard) (NIBSC code: 05/134) and anti-HPV type 18 serum (1st International Standard) (NIBSC code: 10/140) are available to qualified applicants. These materials may be used in immunoassays utilising VLPs and pseudovirion neutralisation tests of adequate sensitivity.

WHO International Standards for Human Papillomavirus (HPV) DNA genotypes HPV16, HPV18, HPV6, HPV11 (NIBSC code: 19/224) are available for use in nucleic acid-based assays.

International Reference Preparations Catalogue

From March 2016 there is a new system for display of WHO prequalified vaccines

List of Prequalified Vaccines

Find out more about the new listing and how to search and display the list on the link below

WHO position paper on HPV vaccination

Human papillomavirus and cervical cancer fact sheet

SAGE Working Group on potential contribution of HPV vaccines and immunization towards cervical cancer elimination

Global Advisory Committee on Vaccine Safety - Committee reports on HPV Vaccines

HPV Vaccine coverage