HIV treatment centres should screen and
treat pre-cancerous anal lesions, UK investigators argue in the
online edition of AIDS. They were
prompted to make this suggestion by research showing that treatment with
imiquimod cream resolved or downgraded high-grade pre-cancerous anal lesions in
61% of HIV-positive gay men.
Although the investigators do not claim
that imiquimod will prevent anal cancer, “we at least know that high grade anal
intraepithelial neoplasia [HG-AIN, pre-cancerous lesions] can be cured. This is
certainly not going to prevent all anal cancers, but it would be a grave error
to await the outcome of long-term natural history studies…the time has come for
all HIV centres to begin screening for and treating AIN.”
Rates of anal cancer are increasing in
patients with HIV. Before the cancer develops pre-cancerous lesions develop in
the anal canal.
Imiquimod cream is a possible treatment for
such lesions and has two distinct advantages: the patient applies it, and it is
suitable for the treatment of extensive lesions. Earlier research has shown
that it is an effective therapy for pre-cancerous lesions in the cervix.
However, there is little information about
the effectiveness of the drug for the treatment of lesions in the anal canal,
and it has not been licensed for use in or around the anus.
Therefore, investigators in London designed
a study involving 64 HIV-positive gay men with high-grade pre-cancerous lesions
in the anal canal.
These patients were randomised to receive
treatment with imiquimod cream three-weekly for four months or a placebo. After
this time all the patients were evaluated and all those who still had disease
present were offered open label imiquimod therapy for a further four months. The
patients were instructed to apply half a sachet of cream on lesions no more
than 2 cm into the anal canal.
There were no significant differences
between the patients in the two arms of the study. All were taking
antiretroviral therapy, the median duration of such treatment being four years.
Approximately 90% had an undetectable viral load and median CD4 cell count was
approximately 350 cells/mm3.
A total of 53 patients (28 in the treatment
arm) completed the study. The most common reason for withdrawal was
dissatisfaction with the 50% chance of being assigned to the placebo arm. Only
one patient withdrew because of side-effects, and one patient (in the placebo
arm) discontinued because his disease progressed and he developed anal cancer.
In the imiquimod group, high-grade lesions
completely resolved in four patients and they remained disease free for a
median of 33 months of follow-up. However, one patient developed a new case of
high-grade lesions after 42 months, probably as a result of re-infection with
high-risk strains of human papilloma virus (HPV).
A further eight patients had their lesions
down-graded to low risk, and one individual completely cleared the disease 48
By contrast, in the placebo group, only one
patient cleared their high-grade lesions. These results showed that imiquimod
therapy was significantly more likely to clear high-grade lesions or lessen the
severity of disease (p = 0.003).
Open-label treatment was provided to 21
patients, twelve of who had been in the placebo arm.
Five individuals experienced a complete
resolution of disease and in a further four patients, the severity of anal
lesions. One of these patients subsequently had complete resolution.
“In summary”, write the investigators,
“thirteen patients have cleared following treatment…sixteen have had a
sustained downgrading low-grade lesions…the total number of patients who have
exhibited prolonged absence of HSIL following treatment with imiquimod is 29
out of 41 patients (61%).
The investigators note that low-grade anal
lesions are usually caused by strains of HPV that do not cause cancer, “for
this reason, the successful clearance of HSIL, leaving only low-grade lesions,
should constitute a considerable reduction in the risk of anal cancer.”
Few HIV treatment centres in the UK
currently screen their patients for pre-cancerous anal cell changes. However,
the investigators believe that it is time to adopt a more aggressive policy.
They emphasise the benefits of detecting and treating the disease, and that
“imiquimod can play a valuable role in the management of anal intraepithelial