A-109 Pathogenesis of anal cancer. (January 2016)

• Record Type: Journal Article
• Authors: Palefsky, Joel
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 71(2016)Supplement 1
• Publication Date: 2016-01
• Subjects: AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/01.qai.0000479582.60625.c0
• Languages: English
• ISSNs: 1525-4135

Abstract

Abstract : Although the risk of anal cancer is increased among HIV-negative men who have sex with men (MSM) compared with the general population, HIV clearly adds to that risk. Unlike most AIDS-defining malignancies, the incidence of anal cancer has increased since the introduction of antiretroviral therapy (ART), and is estimated to be as high as 131/100, 000 among HIV-infected MSM. Anal cancer is now one of the most common non-AIDS defining malignancies (NADM). Anal cancer is very similar biologically to cervical cancer. Like cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSIL) and most cases are associated with HPV 16 infection. Unlike most NADM, anal cancer is potentially preventable through primary prevention (HPV vaccination) and secondary prevention (screening for and treating anal HSIL prior to progression to anal cancer). There are likely to be several mechanisms by which HIV infection contributes to the increased risk of anal cancer including: attenuation of systemic immune response with reduced cell mediated immune response to HPV antigens; local immune response perturbation in the form of chronic HIV-induced low-level tissue inflammation; direct interactions between HIV proteins and HPV within the epithelium including reduction of epithelial tight junction integrity due to tat and gp120, with increased risk of HPV infection due to tat and gp120; and up-regulation of HPV oncogene expression by tat. With evidence for epithelium as a potential reservoir of HIV infection, HIV-HPV interactions may continue despite good HIV control on ART, and may explain in part the lack of impact of ART in reducing the incidence of anal cancer in HIV- infected individuals.