Electrocautery ablation only partially effective as a treatment for high-grade pre-cancerous anal lesions in HIV-positive gay men

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Electrocautery ablation is only partially effective as a treatment for high-grade pre-cancerous anal lesions in HIV-positive gay men and has a high regression rate, investigators from Barcelona report in HIV Medicine.

Approximately two-thirds of patients had some sort of treatment response, but high-grade lesions recurred in a quarter of these individuals. The authors believe these results show that new treatments for pre-cancerous anal lesions are urgently required.

The incidence of anal cancer is high among HIV-positive gay men. Persistent infection with high-risk types of human papillomavirus (HPV) infection is the main cause of anal cancer. HPV infection can cause cell changes that lead to the development of pre-cancerous lesions, often called anal intraepithelial neoplasia (AIN). These lesions are categorised as low-grade (LGAIN) and high-grade (HGAIN), the latter a direct precursor to the development of anal cancer.

Glossary

lesions

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

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.

regression

Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.

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).

topical

Applied directly to the affected area, as opposed to systemic. For example, a cream or lotion, applied to body surfaces such as the skin or mucous membranes inside the vagina or rectum.

 

Studies have found that between 1.3% and 3.2% of people with HIV diagnosed with HGAIN will develop anal cancer within five years.

Standard treatment for HGAIN is electrocautery ablation. Despite this, there are limited data on outcomes in patients receiving this therapy.

Investigators at the Vall d’Hebron University Hospital, Barcelona designed a study to evaluate the safety and effectiveness of electrocautery ablation as a therapy for HGAIN in HIV-positive gay men.

All HIV-positive gay men attending the HIV unit of the hospital between May 2009 and November 2014 were informed of the study and encouraged to take part. A total of 576 individuals underwent screening for anal abnormalities and 126 (22%) were diagnosed with HGAIN. These patients had a median age of 41 years, 81% were taking HIV therapy and two-thirds had an undetectable viral load.

The effectiveness of electrocautery was evaluated in 83 patients. Electrocautery was performed every four to six weeks for a minimum of two to a maximum of four sessions. These two to four sessions were regarded as a treatment cycle.

The effectiveness of treatment was evaluated using biopsy six to eight weeks after each treatment cycle was completed.

A complete response was observed in 33% individuals; a third experienced regression to LGAIN; treatment was unsuccessful in the remaining third of participants.

The majority of patients (81%) had a single treatment cycle. There was a 54% probability that a single cycle would be effective, leading to at least the regression of lesions. The probability of response diminished with each subsequent cycle of treatment.

Patients were then followed for a mean of 12 months after the completion of treatment. A quarter of individuals with a response to therapy developed a recurrence of HGAIN. The mean time to recurrence was 30 months.

No patient developed anal cancer or experienced a serious adverse event. Mild pain and limited bleeding were the most common side effects.

The investigators were unable to identify any factors that predicted response to therapy.

“Taking into account the limited effectiveness and the risk of recurrence with electrocautery ablation, newer strategies are needed to improve the management of HGAIN,” comment the authors. Treatments currently under investigation include infrared coagulation ablation and the application of topical 5-florouracil to lesions to make them more amenable to ablative therapy. A study in HIV-negative men showed that immunisation with the HPV vaccine halved recurrence of HGAIN. The authors urge the evaluation of strategies “based on the combination of different treatments plus the HPV vaccination.”

They conclude that the treatment of anal dysplasia with electrocautery has limited effectiveness and a high rate of recurrence. Therefore, more research is required to develop new strategies for the management of this condition.

References

Burgos J et al. The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men. HIV Medicine. DOI: 10.1111/hiv.12352 (2015).