Stanley et al. BMC Cancer 2012, 12:398 http://www.biomedcentral.com/1471-2407/12/398 history of genital warts and cigarette smoking. Further, in women, additional risk factors are a history of high grade vulvar intraepithelial neoplasia (VIN 3), cervical intraepithelial cancer (CIN 3), vulvar cancer or cervical cancer [4]. Immunosuppressed individuals, such as solid organ transplant recipients and HIV-infected patients, are also more susceptible to HPV-related cancers [5,6]. Most anal SCCs are a consequence of sexually or other- wise acquired infection in the anal mucosa with onco- genic HPV subtypes, predominantly HPV 16 [7]. In Scotland in the period 1975 to 2002 the incidence of anal SCC doubled to 0.37 per 100,000 in men and 0.55 in women [8]. Data from the National Survey of Sexual Attitudes and Lifestyles (NATSAL) in 2000 (quoted in [8]) indicates that in Scotland reported preva- lence of anal intercourse in women (11.16%) was sub- stantially higher than men (0.7%), indicating that this behaviour may partially account for the observed differ- ence in prevalence of anal cancer between the genders. Furthermore, the anatomic proximity of the vaginal introitus to the anus also facilitates non-sexual and auto-inoculation in women via vaginal secretions, digital or fomite transference [9,10]. The proportion of Scottish women reporting the practice of anal intercourse is sig- nificantly lower to similar studies in the U.S., where a prevalence of 22 – 29% has been documented [11,12]. These discrepancies may represent true population be- havioural differences or, perhaps more likely, under- reporting. Even anonymised studies may show significant bias when reporting behavioural aspects, especially when studies are smaller. The overall risk for anal SCC is linked to sexual behaviour between or within genders, not sexual preference; increases in incidence were shown before the advent of the HIV epidemic [3]. The majority of studies of prevalence of anal HPV infection and AIN have been in the MSM cohort, especially HIV-positive MSM, as this is the highest risk group [13], but there are also some data from high-risk HIV-positive and HIV- negative women [14]. However, the paucity of data from the heterosexual male and non-HIV-positive or non- high risk female populations (largest sections of the gen- eral population who make up a substantial number of anal cancer patients) has been a problem in the clinical management of these patients, particularly in determin- ing the rationale and feasibility of instituting a screening program. Nevertheless, it is likely that among men, MSM account for a disproportionate amount of anal intercourse and anal cancer. Recent emerging data suggests that anal HPV (includ- ing intra-anal and peri-anal HPV) infection is common. Nyitray et al. 2008 [15] reported that the prevalence of HPV DNA, detected in 222 heterosexual men, was 16.6% for the anal canal and 21.3% for the perianal area. Of the patients with anal HPV infection, fully 33.3% had Page 2 of 4 an oncogenic high-risk HR-HPV type (as defined by work from cervical cancer and its precursors). A recent follow-up study by the same group, on men from Brazil, Mexico and the USA has extended these findings [16]. In comparing only HIV-negative men (1305 heterosexual versus 176 homosexual), they found anal canal HPV preva- lence of 12.2% and 47.2% in these groups respectively. Two previous studies examining heterosexual men i.e. Van Doornum et al. 1994 [17], and Nicolau et al. 2005 [18], had reported anal HPV DNA prevalences of 35% from 85 men and 8% of men, respectively. The large discrepancies seen are most likely due to differences in technique, sample collection, different cohorts and, in particular, the use of currently available highly sensitive PCR and line blot assays with amplification steps. Anal HPV infection data in HIV-negative women is slightly better documented. The best available data comes from the Hawaii HPV Cohort study; Hernandez et al. 2005 [19] reported a baseline prevalence of 27% anal HPV infection in this cohort. The same group has now reported that during an average follow-up period of 1.3 years, 70% of the women developed incident anal HPV infection [20]. Moscicki et al. 1999 [9] reported that 66.7% of women with abnormal anal cytology had detectable HPV compared to 12.7% of women with nor- mal anal cytology. Finally, Palefsky’s group [14] reported a prevalence of 42% in a cohort of HIV-negative women with high-risk behaviour. The evidence is therefore slowly accumulating that infection of the anal region with HPV in both heterosexual men and non-HIV infected women is relatively common. Natural history studies and data on the role of persist- ent anal infection with HPV in both sexes are consider- ably less compared to that in women for cervical cancer. The largest ongoing longitudinal study in women is that by the investigators of the Hawaii HPV cohort where they showed that in 431 women (followed at 4-monthly intervals), 50% had an incident anal infection during a mean duration of 1.2 years [21]. The median duration for infection with a high-risk subtype was 150 days. This group has further demonstrated that HPV anal infection was likely to be sequentially acquired after initial cervical infection, and that anal infection is cleared in 87% of women within 1 year [22]. This is shorter than the generally reported rate for the cervix (~90% cleared by 2 years) [23]. Interestingly, one study showed that 6 month persistence of HPV 16 was absent in heterosexual men, whereas it oc- curred in 5.1% of MSM patients [24]. These data may partially explain the finding that anal cancer incidence is much lower than that for cervical cancer if we accept the hypothesis that persistent infec- tion with HPV is also required for anal cancer develop- ment. High grade AIN (HGAIN) can be identified using high-resolution anoscopy (HRA) or colposcopy of the