Imiquimod a good treatment for pre-cancerous anal lesions in men with HIV

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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.

Glossary

lesions

Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

anal intraepithelial neoplasia (AIN)

An abnormal growth on the surface of the rectum or anal canal which, when observed with a microscope, suggests that the cells could be malignant (cancerous).

human papilloma virus (HPV)

Some strains of this virus cause warts, including genital and anal warts. Other strains are responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.

open-label

A clinical trial where both the researcher and participants know who is taking the experimental treatment. 

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 months later.

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 neoplasia”.

References

Fox PA et al. A double-blind, randomized controlled trial of the use of imiquimod cream for the treatment of anal canal high-grade anal intraepithelial neoplasia in HIV-positive MSM on HAART, with long-term follow-up data including the use of open-label imiquimod. AIDS, online edition, 2010.