Screening for anal cancer: endpoints needed.

Anal cancer is very rare in the general population, but much more common in well defi ned, high-risk populations, including women with a previous cervical precancer, men who have sex with men (MSM), and individuals with HIV. Infection with carcinogenic human papillomavirus (HPV) has been increasingly recognised to cause anal cancer. In The Lancet Oncology, Dorothy Machalek and colleagues report their fi ndings from a systematic review and meta-analysis of anal HPV infection and associated lesions in MSM, underscoring the disease burden in HIV-positive MSM. They recorded a prevalence of high-risk anal HPV in HIV-positive MSM of 73·5% (95% CI 63·9–83·0). In the same population, the prevalence of high-grade anal intraepithelial neoplasia (AIN) was 29·1% (22·8–35·4) and the estimated annual cancer incidence was 45·9 per 100 000 HIV-positive MSM (95% CI 31·2–60·3). Secondary prevention of cervical cancer by screening for and treatment of precancers has been very successful. Several key factors have made this success possible: suffi ciently high prevalence of precancers, the ability to directly sample the tissue at risk, diagnostic markers that provide suffi ciently reliable risk estimates, and an intervention that removes the tissue at risk, eff ectively interrupting natural history without causing major harm. Although screening to prevent cervical cancer was introduced without full understanding of its natural history, research during the past 30 years has led to the development of a progression model that explains the relevant steps from HPV infection to cervical cancer (fi gure). With the high level of understanding about HPV-related carcinogenesis and experience from cervical cancer screening, eff orts to address screening for anal cancer should have a head start. HIV-positive MSM are a welldefi ned population—they are often followed up closely at specialised clinics to monitor antiretroviral therapy and for surveillance of AIDS-related disease. Machalek and colleagues report a high disease burden in HIVpositive MSM, which is similar to the burden of cervical lesions in women. Targeted sampling of the tissue at risk