Elsevier

The Lancet Oncology

Volume 13, Issue 5, May 2012, Pages 487-500
The Lancet Oncology

Articles
Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis

https://doi.org/10.1016/S1470-2045(12)70080-3Get rights and content

Summary

Background

Men who have sex with men (MSM) are at greatly increased risk of human papillomavirus (HPV)-associated anal cancer. Screening for the presumed cancer precursor, high-grade anal intraepithelial neoplasia (AIN), followed by treatment in a manner analogous to cervical screening, has been proposed. We aimed to assess available data for anal HPV disease that can inform pre-cancer screening programmes.

Methods

We searched PubMed, OVID Medline, and Embase for all studies published before Nov 1, 2011, that reported prevalence and incidence of anal HPV detection, AIN, and anal cancer in MSM. We calculated summary estimates using random-effects meta-analysis.

Findings

53 studies met the inclusion criteria, including 31 estimates of HPV prevalence, 19 estimates of cytological abnormalities, eight estimates of histological abnormalities, and nine estimates of anal cancer incidence. Data for incident HPV and high-grade AIN were scarce. In HIV-positive men, the pooled prevalence of anal HPV-16 was 35·4% (95% CI 32·9–37·9). In the only published estimate, incidence of anal HPV-16 was 13·0% (9·6–17·6), and clearance occurred in 14·6% (10·2–21·2) of men per year. The pooled prevalence of histological high-grade AIN was 29·1% (22·8–35·4) with incidences of 8·5% (6·9–10·4) and 15·4% (11·8–19·8) per year in two estimates. The pooled anal cancer incidence was 45·9 per 100 000 men (31·2–60·3). In HIV-negative men, the pooled prevalence of anal HPV-16 was 12·5% (9·8–15·4). Incidence of HPV-16 was 11·8% (9·2–14·9) and 5·8% (1·9–13·5) of men per year in two estimates. The pooled prevalence of histological high-grade AIN was 21·5% (13·7–29·3), with incidence of 3·3% (2·2–4·7) and 6·0% (4·2–8·1) per year in two estimates. Anal cancer incidence was 5·1 per 100 000 men (0–11·5; based on two estimates). There were no published estimates of high-grade AIN regression.

Interpretation

Anal HPV and anal cancer precursors were very common in MSM. However, on the basis of restricted data, rates of progression to cancer seem to be substantially lower than they are for cervical pre-cancerous lesions. Large, good-quality prospective studies are needed to inform the development of anal cancer screening guidelines for MSM.

Funding

Australian Government Department of Health and Ageing.

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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