Persistent high-risk human papillomavirus (HR-HPV) infection causes cervical cancer, the third leading cause of cancer mortality in women worldwide. High rates of HR-HPV and cervical cancer occur in sub-Saharan Africa and are exacerbated by the HIV epidemic, making prevention of HR-HPV and HIV priorities. Male circumcision reduces HIV acquisition in men. As presented in this article, randomized controlled trial data also demonstrate that male circumcision reduces penile HR-HPV infection in both HIV-negative and -positive men. Male circumcision of HIV-negative men also reduces the prevalence and incidence of HR-HPV infections in their female partners. However, male circumcision of HIV-positive men has no effect on HR-HPV infection in their female partners. These data demonstrate that male circumcision is most effective prior to sexual debut, and the presence of the male foreskin facilitates HIV and HR-HPV infection in men and their female partners. Additional studies that utilize the foreskin mucosa obtained at the time of male circumcision are needed to assess the mucosal microenvironment in HIV and HR-HPV coinfections to develop additional preventive and therapeutic approaches.