||5R03CA203589-02 Interpret this number
||University Of California, San Francisco
||The Microbiome and Anal Cancer Pathogenesis in HIV-Infected Men Who Have Sex with Men
The risk of anal cancer in HIV-infected individuals has markedly increased following the advent of anti-retroviral
therapy, especially in HIV-infected men who have sex with men (MSM). 90% percent of invasive anal
squamous cell carcinomas are associated with human papillomavirus (HPV) infection, of which 80-90% are
associated with HPV type 16. Although anal HPV-16 infection is common in HIV-infected MSM, only a small
fraction of infected men ever develops anal cancer. Why this occurs in some but not others is unknown.
Recent advances in technology have made it feasible to sequence and study the genetic composition, or
?microbiome?, of the community of microbes that colonize different parts of the human body. The expansion of
otherwise commensal bacteria within the gastrointestinal tract is postulated to contribute to inflammation and
carcinogenesis via a variety of pathways including the production of superoxide radicals and toxins. These
imbalances have been associated with disease states such as inflammatory bowel disease and colorectal
This study will determine whether a similar association exists between the anal canal microbiome and high-
grade squamous intraepithelial lesions (HSIL), the precursor to invasive anal cancer. We will determine
whether enrichment of the anal canal with pro-inflammatory bacteria and depletion of anti-inflammatory
bacteria is associated with anal HSIL, particularly because long-term chronic inflammation has been proposed
as a key mediator in HPV cancer pathogenesis. Accordingly our specific aims are: 1) To characterize the
differences in ? and ?-diversity of the anal microbiome in HIV-infected, anal HPV-16 infected, MSM on
effective ART with and without anal HSIL; and 2) To identify specific differences in the composition of the anal
microbiome between HIV-infected, anal HPV-16 infected, MSM on effective ART with and without anal HSIL.
Our results will contribute to our understanding of HPV carcinogenesis and may potentially provide new
approaches to diagnosis and treatment of anal HSIL.