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.
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.
HPV Vaccine Standardization
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
A WHO Reference reagent for anti-HPV 16 serum is available to qualified applicants. This material will serve as the primary biological standard for antibodies to HPV type 16 and may be used in immunoassays utililzing virus-like particles (VLPs) and neutralization tests utilizing pseudovirions of adequate sensitivity. International Standards for HPV type 16 and type 18 DNA are available to qualified applicants. These International Standards should be used to calibrate in-house or working standards for the amplification and detection of HPV types 16 and 18 DNA.
WHO HPV LabNet Training Workshop on HPV Genotyping and HPV Serology Laboratory Performance, Lausanne, Switzerland, 15-18 March 2010
The 2nd WHO HPV Laboratory Network Meeting, WHO, Geneva, Switzerland, 17-19 November 2009
WHO meeting on the standardization of HPV assays and the roles of WHO HPV LabNet in supporting vaccine introduction, WHO, Geneva, Switzerland, 23-25 January 2008
WHO Workshop and practical on Human Papillomavirus (HPV) genotyping and HPV16/18 serology, Lausanne, Switzerland, 4-8 June 2007