Human Papillomavirus Vaccination
Jessica A Kahn Associate Professor of Pediatrics, Cincinnati Children's Hospital Medical Center and the
University of Cincinnati College of Medicine
The results of a randomised, double-blind placebocontrolled
multicentre phase II trial of an HPV
6,11,16,18 vaccine (Merck Research Laboratories,
West Point, PA, USA) were published in 2005.
Women (n=1,106) from Brazil, Europe and the US
who participated in the study received three
preparations of the vaccine containing different
dosages of the four VLPs at day 1, month 2 and
month 6, and subsets were randomised to receive
low-dose vaccine (n=277) or placebo (n=275). In
the according-to-protocol cohort, the incidence of
persistent HPV 6, 11, 16 or 18 infection or disease
associated with these four HPV types decreased by
90% (95% confidence interval 71–97%) in women
who received the low-dose vaccine compared to
placebo. The results were similar in an intentionto-
treat analysis. There were no vaccine-related
serious adverse events. In a larger clinical trial
involving 12,157 young women 16 to 23 years of
age, vaccine efficacy in the per-protocol group was
100.0% (95% confidence interval 80.9–100%) in
preventing HPV 16- or 18-related CIN 2/3 or AIS,
cervical cancer precursor lesions. Vaccination was
98.3% effective (95% confidence interval 90.2–
100.0%) in preventing genital warts associated with
HPV 6, 11, 16 or 18. Data presented recently
demonstrate similarly high effectiveness in
preventing vulvar and vaginal high-grade
precancerous lesions.
Data from clinical trials of the HPV 6,11,16,18
vaccine demonstrate that if women were already
infected with the types contained in the vaccines
prior to vaccination, they were not protected against
disease caused by those vaccine types. However,
those who were infected with one or more vaccinerelated
types before vaccination were protected from
disease caused by the remaining vaccine types. These
results indicate that vaccines should be administered
prior to sexual initiation in order to maximise their
clinical impact. However, immunisation of young
women after sexual initiation is reasonable, because
they may not be infected with all types contained in
the vaccine, and it will not be feasible to test women
for HPV infection with individual HPV types prior
to vaccination.
Several important questions remain about the HPV
vaccines in development. These include the necessity
of booster immunisations after initial vaccination,
efficacy of vaccination in immunocompromised
individuals and in men, cost-effectiveness of
vaccination in different populations, feasibility of
vaccination in developing countries, impact of
vaccination on Pap screening guidelines, and
potential impact of vaccination on sexual behaviours
and compliance with Pap screening. On-going
research should begin to provide answers to these
questions over the coming years.
Potential Public Health Impact of
HPV Vaccination
Prophylactic HPV vaccines could have an enormous
public health impact in the US and worldwide.
Despite a dramatic decline in cervical cancer
incidence and mortality in more developed countries
of the world since implementation of widespread Pap
screening, it remains the fourth most commonly
diagnosed cancer among women in these countries.
It is estimated that in 2006, almost 10,000 new cases
of cervical cancer will be diagnosed in US women
and about 3,700 of these women will die from the
disease. Marked racial and ethnic disparities in
cervical cancer incidence and mortality exist in the
US, which could be decreased with widespread
vaccination. Cervical cancer is the second most
commonly diagnosed cancer and a leading cause of
cancer-related mortality among women in less
developed regions of the world, accounting for
approximately 400,000 diagnoses and 230,000 deaths
per year. Vaccines containing HPV types 16 and 18
could prevent up to 70% of cervical cancers and a
substantial proportion of other anogenital and
aerodigestive malignancies. A vaccine directed
against HPV 6 and 11 could prevent the vast
majority of respiratory papillomas in young children
and anogenital warts. Respiratory papillomas,
although rare, may cause significant upper airway
compromise and necessitate repeated surgical
procedures in children. Genital warts are more
common, with estimated prevalence rates of 1% to
5% in the general population and up to 40% in men
and women attending STI clinics.1, 17, 18 Genital
warts may be difficult to treat and often recur despite
appropriate therapy. An effective HPV vaccine could
also reduce the substantial psychosocial distress and
healthcare costs associated with HPV infection and
related diseases.
