The Study of the Prevention of Anal Cancer (SPANC): design and methods of a three-year prospective cohort study

Abstract

BackgroundThe incidence of human papillomavirus (HPV)-associated anal cancer is increasing in men who have sex with men (MSM). Screening for the presumed cancer precursor, high-grade anal squamous intraepithelial lesions (HSIL) in a manner analogous to cervical cancer screening has been proposed. Uncertainty remains regarding anal HPV natural history and the role of anal cytology and high-resolution anoscopy (HRA) as screening tests. Well-designed cohort studies are required to address these issues.Methods/designThe SPANC study is a prospective study of the epidemiology of low-risk and high-risk anal HPV infection and related cytological and histological abnormalities in HIV-negative and HIV-positive homosexual men aged 35 years and over. The study aims to recruit 600 men from community-based settings in Sydney, Australia. There are six study visits over three years. At the first five visits men undergo a digital ano-rectal examination (DARE), an anal “Papanicolaou” (Pap) test for HPV detection, genotyping and anal cytology, followed by HRA and directed biopsy of any visible abnormalities. The men also complete a behavioural questionnaire before each visit. Questions include a detailed history of sexual behaviour, of anal symptoms, possible anal cancer risk factors and validated quality of life and psychosocial questions. Questionnaires are also completed 2 weeks and 3 months following the provision of test results and include questions on participant experience during the procedure and post-procedure symptoms, including pain and bleeding in addition to quality of life/ psychosocial outcomes.DiscussionRecruitment for the study began in September 2010 and will conclude in mid-2015, with follow up continuing to 2018. Thus far, over 350 men have been recruited from a variety of community-based settings and are broadly representative of the target screening population. The SPANC study is one of only a small number of cohort studies globally to perform HPV, cytology and HRA screening on all participants over multiple time points. The study results will contribute to understanding of the natural history of anal HPV and inform the possible development of guidelines for implementing anal cancer screening programs in this population.

Australian sexually transmissible infection and HIV testing guidelines for asymptomatic men who have sex with men 2014: a review of the evidence

“…121 Studies that include assessing the utility of anal HPV testing to predict the risk of anal precancerous lesions are ongoing and are expected to guide future recommendations. 129 There are few data regarding the impact of HPV infection and HIV acquisition. 130 In a recent meta-analysis of the association of HIV acquisition with HPV infection at a variety of anogenital sites, a significant association was identified.…”

A Composite Cytology–Histology Endpoint Allows a More Accurate Estimate of Anal High-Grade Squamous Intraepithelial Lesion Prevalence

“…16), but changed in January 2015 to 5% in response to evolving opinion that the higher concentration may allow better visualization of squamous intraepithelial lesion (SIL; ref. 10) and visualization using a colposcope on high magnification as published (10,16).…”

“…16), but changed in January 2015 to 5% in response to evolving opinion that the higher concentration may allow better visualization of squamous intraepithelial lesion (SIL; ref. 10) and visualization using a colposcope on high magnification as published (10,16). Following insertion of a plastic anoscope and application of 5% acetic acid, the anal canal was visualized under high-resolution magnification with further application of acetic acid, followed by Lugol iodine, to identify any abnormalities.…”

“…The study was approved by the St Vincent's Hospital Ethics Committee (Sydney, Australia) and all participants gave written informed consent. The study protocol and the study's main objectives have been described in detail previously (16).…”

“…The clinical and laboratory procedures performed in this study have been described in detail previously (16). In brief, a salinemoistened Dacron swab was inserted 3 to 5 cm into the anal canal without direct visualization, and then gradually withdrawn while applying firm circumferential pressure to the wall of the anal canal for approximately one minute.…”