Human Papillomavirus Vaccination
Jessica A Kahn Associate Professor of Pediatrics, Cincinnati Children's Hospital Medical Center and the
University of Cincinnati College of Medicine
Human papillomavirus (HPV) is the most common
sexually transmitted infection (STI) in the US: it is
estimated that 75–80% of adult men and women
will be exposed to genital HPV infection at some
point in their lives, and approximately six million
new infections occur yearly. In sexually active
adolescent girls, the risk of acquiring HPV
infection over a two-year period is as high as 82%.
Risk factors for HPV infection include early age of
sexual initiation, number of sexual partners,
partners’ number of sexual partners, cigarette
smoking, immunosuppression (e.g. HIV infection,
immunosuppressive medications) and infection
with other STIs, such as genital herpes. Infection is
through skin-to-skin contact; penetrative sexual
intercourse is not necessary for transmission.
Infection often is acquired within a few months of
sexual initiation, and is common even among those
with only one sexual partner.
Over 130 HPV types have been identified, and
approximately 40 of these cause genital infections.
Infection with low-risk types, such as 6 and 11, may
cause anogenital warts. Vertical transmission of lowrisk
HPV types from mother to neonate may cause
recurrent respiratory papillomatosis (RRP), which
are warts in the upper airway of young children.
Approximately 90% of genital warts and almost all
cases of RRP are caused by these two HPV types.
Genetic and epidemiologic studies have
demonstrated that infection with high-risk types,
such as 16 and 18, is a necessary cause of cervical
cancer. At least 99% of cervical cancers contain one
or more of the 15 recognised high-risk types, and
approximately 70% contain HPV types 16 or 18.
Natural history studies have demonstrated that
persistent infection with high-risk HPV types,
indicating on-going viral replication, is the key factor
in the development of cervical cancer precursor
lesions. These include moderate/severe cervical
intraepithelial neoplasia (CIN 2/3), precursors to
cervical squamous cell carcinoma, and
adenocarcinoma in situ (AIS), a precursor to cervical
adenocarcinoma. HPV infection also causes up to
50% of vulvar and vaginal cancers in women and a
proportion of penile and anal cancers in men. Head,
neck, and oesophageal cancers have also been linked
to HPV infection.
HPV Vaccines
Vaccines that prevent infection with the most
common HPV types have been developed and are
being evaluated for efficacy in large, phase III clinical
trials. These vaccines are comprised of virus-like
particles (VLP), recombinant viral capsids that are
identical morphologically to HPV virions, but
contain no viral DNA. Thus, they can induce a
neutralising antibody response but pose no risk of
HPV infection or cancer.
These vaccines target HPV types 16 and 18, with or
without types 6 and 11. The results of a randomised,
double-blind, placebo-controlled trial evaluating the
clinical efficacy of an HPV-16,18 vaccine (Glaxo-
SmithKline Biologicals, Rixensart, Belgium), were
published in 2004. A total of 1,113 women 15 to 25
years of age were randomised to receive
HPV-16,18 vaccine or placebo at day 0, month 1
and month 6. In the according-to-protocol analysis,
which included those participants who followed the
research protocol closely, the vaccine was 100%
effective (95% confidence interval 47.0–100%)
against persistent infection with HPV 16, 18, or
both. The vaccine was 91.6% effective (95%
confidence interval 64.5–98.0%) against incident
infection with HPV 16, 18, or both. In the
intention-to-treat analysis, which included all
participants who received at least one dose of vaccine
or placebo, vaccine efficacy was 95.1% (95%
confidence interval 63.5–99.3%) against persistent
cervical infection with HPV 16, 18, or both. Efficacy
was 92.9% (95% confidence interval 70.0–98.3%)
against HPV 16- or 18-related Pap abnormalities.
There were no serious adverse events related to
vaccination. Recent data indicate that both antibody
levels and clinical efficacy are sustained for at least 4.5
years after vaccination.
Additional studies are on-going to evaluate vaccine
efficacy, including studies of older women. Data
presented at the 2006 American Society of Clinical Oncology (ASCO) annual meeting demonstrated
that 100% of women 15 to 55 years of age who were
vaccinated developed an antibody response to HPV
16 and 18 after completing vaccination.
