High prevalence and incidence of anal pre-cancerous lesions in men with HIV; HAART has little impact

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Prevalence and incidence of high-grade pre-cancerous anal lesions in HIV-positive men who are taking antiretroviral therapy are high, Canadian investigators report in the online edition of Clinical Infectious Diseases.

A low nadir CD4 cell count and infection with HPV types 16 and 18 were associated with an increased risk of developing high-grade pre-cancerous anal lesions (AIN-2, 3).

The investigators hope that their findings will help identify patients who have a higher risk of HPV-associated anal disease.

Glossary

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.

lesions

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

nadir

Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

anoscopy

Examination of the anal canal and lower rectum using a short speculum (anoscope).

Rates of HIV-related opportunistic infections have fallen significantly since the introduction of antiretroviral therapy.

However, the incidence of anal cancer is increasing.

Most of the information about the risk factors for this disease in HIV-positive gay men was obtained during the era before effective antiretroviral therapy became available. These include high-grade pre-cancerous lesions, infection with HPV 16 and 18, multiple HPV infections and CD4 cell count.

 Investigators from the Canadian Human Immunodeficiency and Papilloma Virus Research Group (HIPVIRG) wanted to establish a comprehensive understanding of the risk factors for progression to AIN 2 and 3. They also wished to see if treatment with anti-HIV drugs had any impact on disease progression.

A total of 247 men who were taking or about to initiate antiretroviral therapy were recruited to the study between 2002 and 2005.

The patients had swabs to see if they had anal HPV infection, and if present further tests were conducted to determine whether strains associated with anal cancer were present.

At baseline and then at intervals of six or twelve months the patients underwent high-resolution anoscopy to check for pre-cancerous lesions.

Median age at baseline was 43 years, 38% were smokers (a risk factor for HPV-related cancers), 90% were already receiving HIV therapy, median CD4 cell count was 380 cells/mm3 and 54% had an undetectable viral load.

On entry to the study, 19% of patient had normal anal cytology, 50% had low grade lesions, AIN 2 was present in 17%, and 13% had AIN 3.

Follow-up was for a median of 38 months. High-grade anal lesions were identified at least once in 54% of patients. However, only two patients developed anal cancer.

A total of 147 who did not have AIN 2 or 3 at follow-up were followed so that the investigators could calculate rates of progression and risk factors.

Incident high-grade lesions were diagnosed in 57 patients, and this provided a rate of 12.8 cases per 1000 months of follow-up. The cumulative incidence was 23% after two years and 37% after 36 months.

Analysis that included men whose first two anoscopy results negative for high grade lesions showed a progression rate of 7 cases per 1000 person months and an 24-month incidence of 21%.

Risk factors for the development of AIN 2 or 3 included older age (40-49 years, OR = 3.09; 95% CI, 1.12-8.52; over 50, OR = 4.78; 95% CI, 1.29-17.73); a nadir CD4 cell count below 50 cells/mm3 (OR = 14.40; 95% CI, 1.45-143.58); infection with HPV 16 or 18 (OR = 14.18; 95% CI, 3.51-57.32), and infection with HPV 16 and 18 (OR = 31.03; 95% CI, 5.68-169.60).

Current CD4 cell count was not associated with disease progression, and there was only very modest evidence that therapy with anti-HIV drugs had a protective effect. Incidence of AIN 2 and 3 was slightly reduced among patients who had been taking HIV treatment for four or more years.

“We…found that men who had received their current HAART regimen for a longer time had a lower risk…especially after adjusting for nadir CD4 cell counts. This suggests that, although one cannot fully recover from HIV-induced immune deficiency, HAART could have some beneficial effect in reducing the risk of AIN-2,3,” comment the authors.

They conclude, “our study confirms the high prevalence and incidence of AIN-2,3 among HIV-infected MSM.”

Patients with a low nadir CD4 cell count could, the investigators believe, especially benefit from screening for pre-cancerous lesions. In addition, “typing could also be useful as an adjunct to cytological examination in primary screening.”

The author of the accompanying editorial believes the study “may bring us closer to the identification of biological markers of AIN progression and provide a practical screen tool for anal HPV disease.

References

 de Pokomandy A et al. HAART and progression to high-grade anal intraepithelial neoplasia in men who have sex with men and are infected with HIV. Clin Infect Dis, online edition, doi: 10.1093/cid/cir064, 2011 (click here for the free abstract).

Severini A et al. Anal intraepithelial neoplasia in men living with HIV in the era of highly active antiretroviral therapy. Clin Infect Dis, online edition, doi: 10.1093/cid/cir070, 2011 (click here for the full text [£]).