Vaccination against cancer-associated
strains of human papillomavirus (HPV) could be highly effective at preventing
pre-cancerous anal cell changes in men living with HIV, according to research
published in the online edition of the Journal
of Infectious Diseases.
The cross-sectional study showed that almost
all cases of high-grade anal intraepithelial neoplasia (HGAIN) – the cell
changes that occur in the anus prior to the development of anal cancer – were
caused by strains of HPV covered by licensed or investigational vaccines. The
investigators believe their findings “can inform assumptions of HPV vaccine
efficacy and cost-effectiveness and decision-analysis models.”
There is a high incidence and prevalence of
pre-cancerous anal lesions and anal cancer in HIV-positive gay men. Vaccines
that provide a high level of protection against the HPV genotypes with the
highest risk of anal and genital cancers have been licensed. Research is
currently underway into potential vaccines that provide even broader protection.
HPV vaccination is currently targeted at adolescent girls. There has been
considerable debate about the efficacy and cost-effectiveness of vaccinating
adult, HIV-positive gay men.
Doctors in San Francisco therefore designed
a study involving 363 HIV-positive gay men who received care between 2009 and
2010. Each patient was screened for the presence of pre-cancerous anal lesions
and provided samples for HPV genotyping. Several HPV genotypes have been
associated with pre-cancerous anal cell changes. These include HPV 16/18/31/33/45/52/58.
These genotypes are covered by licensed or investigational vaccines.
Multiple HPV genotypes are often present in
pre-cancerous lesions. The investigators therefore developed a model that
allowed them to calculate the proportion of cases of HGAIN attributable to
individual HPV genotypes. “We used this information to predict the potential
efficacy of prophylactic HPV vaccines, under the assumption that vaccination
would occur before natural infection and seroconversion,” explain the authors.
The study participants had a median age of 53 years.
They were highly sexually experienced. The median age at first anal sex was 20
years; 40% reported over 40 lifetime anal sex partners; and 15% reported three
or more partners for anal sex within the previous six months. The majority (94%) were taking antiretroviral therapy. Approximately three-quarters
(72%) had a CD4 cell count above 350 cells/mm3 and 90% had an
undetectable viral load.
The majority of the patients (59%) had
pre-cancerous anal lesions, including 30% with HGAIN. Three-quarters of
individuals were infected with a high-risk HPV genotype. HPV16 was the most
common individual genotype, present in 28% of patients.
“HPV16, which has been shown to cause an
even greater proportion of anal cancers than cervical cancers, is seen as the
dominant genotype in HGAIN disease categories,” write the authors. “Other HPV
genotypes vary substantially in their prevalence and attribution estimates in
The prevalence of high-risk HPV genotypes
increased significantly according to the severity of pre-cancerous anal lesions
(p < 0.05). Patients with more severe disease were also significantly more
likely to be infected with multiple high-risk HPV genotypes. Up to seven
individual high-risk genotypes were identified in individual lesions.
Depending on the number of infecting HPV
genotypes, the proportion of cases of HGAIN attributed to HPV16/18 and other
individual genotypes covered by currently licensed vaccines ranged between 12
and 62%. The fraction of cases attributed to the individual genotypes targeted
by investigational vaccines ranged between 39 and 89%.
Taken together, 95% of all high-grade lesions
were attributed to high-risk genotypes. The licenced quadrivalent vaccine
covered 71% of genotypes present in the highest-grade lesions, whereas the
investigational nonavalent vaccine would have provided protection against 89%
of HPV genotypes in high-grade lesions.
“The prevention of anal cancer in high-risk
populations such as HIV-infected MSM [men who have sex with men] remains an
urgent priority,” conclude the investigators. “The analytical framework presented
in this study can be applied to larger and pooled efforts to improve
estimations of the causative role of individual genotypes and expand our
understanding of the natural history of and prevention approaches for anal