Human papillomavirus and HPV vaccines: a review
FT Cutts, S Franceschi, S Goldie, X Castellsague, S de Sanjose, G Garnett, WJ Edmunds, P Claeys, KL Goldenthal, DM Harper, L Markowitz
Cervical cancer, the most common cancer affecting women in developing countries, is caused by persistent infection with “high-risk” genotypes of human papillomaviruses (HPV). The most common oncogenic HPV genotypes are 16 and 18, causing approximately 70% of all cervical cancers. Types 6 and 11 do not contribute to the incidence of high-grade dysplasias (precancerous lesions) or cervical cancer, but do cause laryngeal papillomas and most genital warts. HPV is highly transmissible, with peak incidence soon after the onset of sexual activity.
A quadrivalent (types 6, 11, 16 and 18) HPV vaccine has recently been licensed in several countries following the determination that it has an acceptable benefit/risk profile. In large phase III trials, the vaccine prevented 100% of moderate and severe precancerous cervical lesions associated with types 16 or 18 among women with no previous infection with these types. A bivalent (types 16 and 18) vaccine has also undergone extensive evaluation and been licensed in at least one country. Both vaccines are prepared from non-infectious, DNA-free virus-like particles produced by recombinant technology and combined with an adjuvant. With three doses administered, they induce high levels of serum antibodies in virtually all vaccinated individuals. In women who have no evidence of past or current infection with the HPV genotypes in the vaccine, both vaccines show > 90% protection against persistent HPV infection for up to 5 years after vaccination, which is the longest reported follow-up so far. Vaccinating at an age before females are exposed to HPV would have the greatest impact. Since HPV vaccines do not eliminate the risk of cervical cancer, cervical screening will still be required to minimize cancer incidence. Tiered pricing for HPV vaccines, innovative financing mechanisms and multidisciplinary partnerships will be essential in order for the vaccines to reach populations in greatest need.