Human papillomavirus vaccines are a promising technology for primary prevention of cervical cancer and the other HPV-related diseases, but achieving high rates of vaccination in the age group targeted for vaccination presents a challenge. Pediatricians play a vital role in implementing national recommendations for HPV vaccination for children and adolescents.
Human papillomavirus (HPV) vaccines are a promising technology for primary prevention of cervical cancer and other HPV-related diseases, but achieving high rates of vaccination in the age group targeted for vaccination presents a challenge. Pediatric clinicians play a critical role in the implementation of national recommendations for HPV vaccination for children and adolescents.
The Food and Drug Administration (FDA) approved a quadrivalent HPV vaccine (Gardasil, Merck) in June 2006 for use in girls and women and in October 2009 for use in boys and men. The agency approved a bivalent HPV vaccine (Cervarix, GlaxoSmithKline) in October 2009 for use in girls and women.
In this article, we briefly review HPV infection and HPV vaccines, describe current indications and US recommendations for the quadrivalent and bivalent vaccines, discuss ongoing research that may affect future vaccine indications, and suggest strategies that pediatric clinicians can use for successful implementation of HPV vaccine recommendations.
HPV is an extremely common sexually transmitted infection (STI): it is estimated that at least 80% of men and women acquire an HPV infection during their lives.1 As with other STIs, HPV disproportionately affects adolescent and young adult women. In a recent study of US women, 25% of 14- to 19-year-olds and 45% of 20- to 24-year-olds were infected with at least 1 type of HPV.2 HPV is often acquired within a few months of sexual initiation, even among young women with only 1 sexual partner.3 The number of sexual partners is the single most important risk factor for HPV acquisition.4
There are more than 130 known HPV genotypes, and approximately 40 of these infect the anogenital or oropharyngeal mucosa. The viral genome encodes the 2 nucleocapsid proteins L1 and L2 and at least 6 early proteins.5,6 The expression of proteins E6 and E7 is associated with carcinogenesis. HPV infects basal epithelial cells of the squamous epithelium through microabrasions in the skin or mucosa. An initial phase of genome amplification is followed by an episomal maintenance phase. As infected basal cells enter the suprabasal compartment, abundant expression of early and late genes occurs. Viral particles are assembled in the upper layer of the squamous epithelium, and virions are then released and infect neighboring cells.
Although most HPV infections are asymptomatic, a proportion of infected individuals will develop clinical disease. HPV types are classified as low risk and high risk. Infection with low-risk types HPV-6 or HPV-11 causes approximately 90% of anogenital warts and recurrent respiratory papillomatosis (RRP).7 Infection with high-risk types such as HPV-16 and HPV-18 may cause cervical intraepithelial neoplasia (CIN), cervical carcinoma in situ, and cervical cancer, as well as other cancers. Lesions most likely to progress to cervical cancer include CIN 2 (moderate dysplasia) and CIN 3 (severe dysplasia). HPV-16 and HPV-18 cause approximately 50% of CIN 3 lesions and 70% of cervical cancers.8 Infection with high-risk HPV is thought to cause virtually 100% of cervical cancers; approximately 90% of anal cancers; at least 50% of vulvar, vaginal, and penile cancers; and a subset of oropharygeal cancers.9-11
In the United States, approximately 13,000 women are diagnosed with cervical cancer and approximately 5,200 die each year of cervical cancer.12 Approximately 50% to 70% of women diagnosed with cervical cancer were either never screened with a Pap test or were not screened within the 5 years before diagnosis.13,14 Worldwide, cervical cancer is the second most common cancer in women: approximately 490,000 women are diagnosed and 270,000 die from cervical cancer annually.15