Anal human papillomavirus infection and associated disease in homosexual men

Abstract

The incidence of human papillomavirus (HPV)-associated anal cancer is increasing among men who have sex with men (MSM). Screening for the presumed anal cancer precursor, high-grade squamous intraepithelial lesions (HSIL) has been proposed. This has been challenged because the natural history of HSIL is not yet well understood. This thesis presents a series of epidemiological studies within the theme of anal HPV infection and associated disease in homosexual men. A large part of the work draws on baseline data from a large longitudinal study of the natural history of HPV infection in homosexual men. A systematic review and meta-analysis of studies on anal HPV and HSIL prevalence in MSM confirmed that anal HPV and anal canal precursor lesions were very common in this population, regardless of HIV status. However data on natural history is sparse. Limited available evidence suggests that only a minority of lesions will ever progress to anal cancer. This key finding provides an ethical justification for prospective studies of HSIL to identify men with HSIL, who are at highest risk of persistent disease. The Study of the Prevention of Anal Cancer (SPANC) is uniquely placed to contribute significantly to the understanding of anal HPV infection and associated disease and inform the development of evidence-based anal cancer screening guidelines in this population. Thus far, over 350 men have been recruited from a variety of community-based settings and are broadly representative of the target study population. The first step in understanding natural history, involves the ability to accurately detect anal HPV-related disease. Combining cytology and histology results will lead to the diagnosis of more HSIL compared with cytology only and histology only endpoints. A corresponding increase in HPV16 prevalence with increasing composite endpoint grade provides support for composite-HSIL as a biologically meaningful category, which represents an accurate measure of significant HPV-related HSIL. In this well-defined community-recruited cohort of HIV-positive and HIV-negative homosexual men, composite-HSIL was common, irrespective of HIV status. Behavioural factors and immune dysfunction are likely to contribute to the high prevalence of lesions among homosexual men, largely via the elevated risk of anal HPV acquisition and persistence.