ArticlesAnal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis
Introduction
Infection with high-risk types of human papillomavirus (HPV) causes more than 80% of cases of anal cancer,1 and is recognised as a necessary cause of nearly 100% of cases of cervical cancer.2, 3 During the past 20–30 years, the incidence of anal cancer has been increasing. Populations at increased risk include women with previous cervical HPV-related disease,4 immune suppressed transplant recipients, and HIV-positive individuals.5 Incidence of anal cancer is highest in men who have sex with men (MSM), who are about 20 times more likely than heterosexual men to develop the disease.6 HIV-positive MSM are at even greater risk.7 In view of the increasing health burden of anal cancer in MSM and its similarities to cervical cancer, some researchers have proposed an anal cancer screening programme for this population.8 It would be based on cytological detection of HPV-related abnormalities, or possibly by direct detection of HPV-related biomarkers, followed by histological confirmation of the presumed cancer-precursor lesion high-grade intraepithelial neoplasia (AIN), and treatment. Since the implementation of population-based screening programmes for cervical cancer, there has been a substantial reduction in the incidence and mortality from this malignancy.9 In the past 5 years, HPV vaccination has been introduced for women in several countries, with the aim of further reducing the incidence of cervical cancer. In Australia, where there has been a rapid and widespread uptake of the quadrivalent HPV vaccine by women younger than 27 years, striking reductions in cervical high-grade precancerous lesions in young women have been reported, in addition to a rapid decrease in the prevalence of genital warts.10, 1 A parallel, although lesser, decrease in genital warts in young heterosexual men10 suggests that vaccination of women and girls will lead to a reduction in HPV-related morbidity in heterosexual men through herd immunity. Unfortunately, MSM will not benefit from such herd immunity, so other approaches are needed to reduce HPV-related morbidity in this population. Universal vaccination of adolescent boys (before sexual debut) has enormous potential to prevent HPV-related morbidity in the future,12 but before such potential is realised, alternative approaches such as screening are needed.
Cervical screening based on detection of cytological abnormalities has existed for 60 years.13 Since the discovery of HPV, many observational studies have described the natural history of cervical HPV infection and of cytological abnormalities.14 Although many studies have estimated the prevalence and incidence of anal HPV infection, anal cytological abnormalities, and AIN in MSM, the natural history of progression of anal HPV infection to anal cancer in MSM is unclear. There is no consensus as to how widespread anal high-risk HPV infection is; the prevalence and significance of AIN; and the rate of progression of AIN to anal cancer.
This systematic review and meta-analysis presents a summary of all published estimates of data for anal HPV detection, cytological and histological abnormalities, and anal cancer in HIV-positive and HIV-negative MSM.
Section snippets
Search strategy and selection criteria
We did a systematic review without language restrictions for all peer-reviewed, published studies of the prevalence and incidence of anal HPV infection and anal cytological and histological neoplastic abnormalities, and the incidence of anal cancer in MSM published before Nov 1, 2011. We searched PubMed, OVID Medline, and Embase using the following combined heading search strategy: “anal intraepithelial neoplasia” OR “AIN” AND “men who have sex with men” OR “MSM” OR “homosexual men”. For the
Results
We identified 729 studies, of which 53 were included in our meta-analysis (figure 1 and table). Three studies were excluded from the analysis of anal HPV prevalence because their recruitment strategies resulted in non-representative samples (appendix p 9). One of these studies was restricted to MSM with fewer than five lifetime sexual partners, and two clinic-based studies recruited only patients with evidence of HPV-associated anal lesions. Three studies in which high-resolution anoscopy was
Discussion
In the studies of MSM we reviewed, most men had detectable anal canal HPV, and histologically proven high-grade AIN was present in 20–30% of all men. HIV-positive MSM were consistently more affected by HPV and HPV-related abnormalities than were HIV-negative MSM, and they had a worryingly high incidence of anal cancer. These anal cancer rates are similar to the incidence of cervical cancer in the general female population before the introduction of national cervical screening programmes,76 and,
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