The genital wart
vaccine Gardasil significantly
reduces the risk of high-grade pre-cancerous anal lesion recurrence in men who
have sex with men, US investigators report in the online edition of Clinical Infectious Diseases.
The vaccine reduced
the risk of lesion recurrence by approximately 50% in the first two years after
immunisation. There was some evidence that the protective effects of the
vaccine waned after this point.
“This is the first
study to demonstrate an association between Gardasil
after primary disease and decreased risk of recurrent HGAIN [high-grade
intraepithelial neoplasia],” comment the investigators, who believe the vaccine
may be “an effective post-treatment adjuvant to prevent recurrent HGAIN”.
High-risk strains of
human papillomavirus are the main cause of anal and cervical cancer. The
quadrivalent human papillomavirus vaccine (Gardasil)
is highly effective at preventing infection with these strains. Rates of anal
cancer are elevated in gay and other men who have sex with men.
However, studies into
the vaccine’s effectiveness recruited younger patients with no history of human
papillomavirus-related disease. Little information is available on the
vaccine’s ability to prevent the recurrence of high-grade pre-cancerous cell
changes in the anus.
Investigators in New
York therefore undertook a study involving a cohort of 202 middle-aged
HIV-negative gay and other men who have sex with men, all of whom had undergone
therapy for human papillomavirus-related high-grade pre-cancerous anal cell
A total of 88 men
(44%) were vaccinated with Gardasil;
the remaining men were unvaccinated. Investigators compared the risk of the
recurrence of pre-cancerous lesions after one, two and three years in the
vaccinated and unvaccinated men.
The study was
conducted between 2007 and 2010.
Men who received the
vaccine were significantly younger than those who remained unvaccinated (37 vs
42 years, p = 0.02).
pre-cancerous lesions recurred in 12 vaccinated men and 35 unvaccinated
men. The rates of recurrence in the vaccinated men was 10.2 per 100 person-years, against an incidence of 15.7 per 100 person-years in the unvaccinated
first set of statistical analysis examined the factors associated with the
recurrence of disease after two years. Infection with high-risk strains of
human papillomavirus had a significant association with the recurrence of anal
lesions (p = 0.003). In contrast, Gardasil
significantly reduced the risk of disease recurrence (p = 0.05).
analysis that took into account potential confounding factors confirmed that
infection with high-risk virus strains increased the risk of disease recurrence
after one (p = 0.006), two (p =0.004) and three years (p = 0.003).
This same analysis
showed that the risk of recurrence was reduced by Gardasil after one (p = 0.01) and two years (p = 0.05) of
follow-up. However, the protective effect of the vaccine after three years was
of only borderline significance (p = 0.06).
Analysis was then
restricted to the 105 patients who tested positive for high-risk strains of
human papillomavirus. A total of 47 (45%) patients received the vaccine.
The incidence of
disease recurrence was 15.4 per 100 person-years in the vaccinated patients,
compared to 28.3 per 100 person-years in the unvaccinated men.
Once again, the
vaccine was found to significantly reduce the risk of disease recurrence after
one and two years (p = 0.02 and p = 0.05 respectively) and the protective
effect was of borderline significance at year three (p = 0.06).
At year one, the
vaccine reduced the risk of disease recurrence by 60% (HR = 0.40; 95% CI,
0.19-0.86); by 53% at year two (HR= 0.47; 95% CI, 0.22-1.00); and by 52% at
year three (HR = 0.48; 95% CI, 0.22-1.04).
“MSM with a history of
treated HGAIN who received [Gardasil]
had a decreased risk of recurrent HGAIN compared to men who did not receive the
vaccine,” write the authors.
However, they add:
“Whereas [Gardasil] appears effect in
preventing recurrent disease, it is not effective at preventing all
recurrence.” They believe that this disease could have been associated with
non-high-risk strains of virus, or have reoccurred because “viral integration into the host
genome had already occurred and the vaccine is not effective after
The authors believe
their findings are potentially of public health significance. “If our results
are confirmed by a randomized, placebo-controlled trial, then indications for
vaccination and the age of the target population should be expanded.”