english.prescrire.org > Spotlight > Archives : 2007 > Human papillomavirus vaccine for genotypes 6, 11, 16 and 18

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Most cases of high-grade anogenital dysplasia and malignancy are caused by human papillomavirus (HPV) genotypes 16 and 18. Anogenital papilloma and condyloma acuminata are mainly caused by HPV6 and HPV11.

A recombinant vaccine covering these four genotypes is now marketed in the European Union for the prevention of condyloma, precancerous lesions, and cancers of the female lower genital tract.

A three-dose vaccination schedule (0, 2 and 6 months) elicits an immune response in almost all women, but the minimum antibody titre required for clinical protection is not known. Immune protection lasts at least 5 years, but no one knows what happens after that time.

Three double-blind randomised placebo-controlled trials involving a total of about 18 000 women aged 16 to 23 had sufficiently similar designs to pool results for analysis. Nearly all (around 98%) of women not yet infected with papillomavirus of a genotype covered by the vaccine were protected from dysplasia caused by one of these genotypes. The vaccine did not affect dysplasia caused by other genotypes, nor was it effective in women who were already infected. In total, among women not yet infected with a papillomavirus genotype covered by the vaccine, the vaccine prevented about 38% of high-grade dysplasias of all types (0.5 versus 0.8 cases per 100 woman-years).

The vaccine also markedly reduced the incidence of genital warts and high-grade vulvar and vaginal dysplasia. There are no data on efficacy beyond 4.5 years.

These results are somewhat undermined by methodological problems, such as follow-up lasting only a maximum of 4.5 years whereas cervical cancer takes much longer to develop. In addition, there were very few cases of dysplasia in each trial, and results were largely based on post hoc subgroup analyses.

Apart from local reactions, which occurred in more than 80% of vaccinated women, the only adverse effect of papillomavirus vaccination was fever (12.9% of those on the vaccine versus 11% on placebo).

There is no evidence thus far that prenatal exposure due to HPV vaccination during the month preceding conception is harmful.

The clinical results are promising but further follow-up is needed to answer ongoing questions, such as the incidence of cervical cancer after vaccination and the duration of protection. Cervical cancer screening remains necessary, even for vaccinated women, and a continued need exists for measures designed to prevent all sexually transmitted diseases.

©Prescrire July 2007

Source: Prescrire International 2007; 16 (89): 91-94.

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