No abstract

Human papillomavirus (HPV) infection is associated with essentially all cervical cancers, 80-90 % of anal cancers, and a high proportion of oropharyngeal, vaginal, penile, and vulvar cancers. Malignancy is preceded by the development of precancerous lesions termed high-grade squamous intraepithelial lesions (HSIL). Men and women with human immunodeficiency virus (HIV) infection are at high risk of HPV-related malignancies. The incidence of anal cancer in particular has markedly risen during the antiretroviral era due to the increased longevity of patients with HIV and the absence of anal malignancy screening programs. HIV infection may facilitate initial HPV infection by disrupting epithelial cell tight junctions. Once infection is established, HIV may promote HSIL development via the up-regulation of HPV oncogene expression and impairment of the immune response needed to clear the lesion. HIV-infected women should be screened for cervical HSIL and cancer, and HIV-infected men and women should be considered for anal screening programs.

Regulation of inflammatory responses is critical to progression of organ-specific autoimmune disease. Although many candidate cell types have been identified, immunoregulatory activity has rarely been directly assayed and never from the CNS. We have analyzed the regulatory capability of Gr-1high neutrophils isolated from the CNS of mice with experimental autoimmune encephalomyelitis. Proportions of neutrophils were markedly increased in the CNS of IFN-γ-deficient mice. Strikingly, CNS-derived neutrophils, whether or not they derived from IFN-γ-deficient mice, were potent suppressors of T cell responses to myelin or adjuvant Ags. Neutrophil suppressor activity was absolutely dependent on IFN-γ production by target T cells, and suppression was abrogated by blocking NO synthase. These data identify an immunoregulatory capacity for neutrophils, and indicate that interplay between IFN-γ, NO, and activated Gr-1high neutrophils within the target organ determines the outcome of inflammatory and potentially autoimmune T cell responses.

Cancer and HIV are inextricably linked. Although the advent of antiretroviral therapy has led to a marked decline in the incidence of malignancies classically linked to immunosuppression (AIDS-defining malignancies, or ADMs), this decrease has been accompanied by a concomitant rise in the incidence of other malignancies (non-AIDS-defining malignancies, or NADMs). Population-based cancer registries provide key information about cancer epidemiology in people living with HIV (PLWH) within resource-rich countries. The risk for NADMs is elevated in PLWH compared with the general population, particularly for lung and anal cancers. Contributory factors include tobacco use, coinfection with oncogenic viruses such as human papillomavirus, and potentially direct effects of HIV itself. Data from resource-poor countries are limited and highlight the need for more studies in countries where the majority of PLWH reside. Strategies for early cancer detection and/or prevention are necessary in PLWH.