Anal intraepithelial neoplasia in HIV+ men: Epidemiology, cancer risk stratification and prevention of recurrences

Anal cancer is relatively rare in the general population, but incidence rates have been steadily increasing over the past decades. In specific risk groups, most importantly human immunodeficiency virus-positive (HIV+) men who have sex with men (MSM), the burden of anal cancer is disproportionally high. Anal cancer is caused by a persistent human papillomavirus (HPV) infection. Anal precancerous lesions called high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent in HIV+ MSM. Therefore, preventing development of cancer from precancerous lesions through screening for and treatment of HGAIN in this risk group is under debate. However, current screening procedures are suboptimal.
In this thesis, we increased the understanding of the epidemiology of anal cancer in general and within high-risk populations in particular. Next, we investigated several novel and promising strategies to overcome drawbacks of current screening. In particular, we examined biomarkers for cancer risk stratification of HGAIN to identify lesions with a high risk of progression to cancer, allowing a more targeted treatment approach, thereby preventing overtreatment of lesions with a low risk of progression. We evaluated biomarkers based on host cell DNA methylation as well as immunohistochemical markers applicable on anal tissue samples. In the last part of this thesis we evaluated the efficacy of HPV vaccination to prevent recurrences of HGAIN in HIV+ MSM. This work will help improve the effectiveness of anal cancer screening and quality of life of people at risk for anal cancer.