| Summary: | Background: Anal intraepithelial neoplasia (AIN) is associated with high-risk human papillomavirus (hrHPV) infection and is a precursor to anal cancer. Factors other than hrHPV are likely to be involved in causing AIN and further study of cofactors is required. Methods: A surgical database of patients having anal warts removed was established at Royal Perth Hospital in 1995 and epidemiological information concerning age, sex, sexual preference, history or clinical evidence of gonorrhoea or chlamydia infection and serological evidence of HIV-1, HSV-2, hepatitis B or C virus infection and syphilis has been prospectively collected since then. Three hundred and fourteen patients underwent 457 operations from June 1995 to November 2016. Histopathology and hrHPV testing using the Digene Hybrid Capture 2 (HC2) method were performed at the time of surgery. Results: hrHPV alone was associated with high-grade squamous epithelial lesions (HSIL) (OR=4.65, p<0.001). Amplification of HSIL risk was found when hrHPV infection occurred with HIV-1 (OR=11.1) or HSV-2 (OR=7.85) infection; current or previous gonorrhoea (OR=6.45) or syphilis (OR=5.58); and some other infections. Conclusions: HrHPV is a sufficient cause of anal HSIL but seropositivity for HIV-1, HSV-2, T. pallidum, HBV, HCV infections and a history of gonorrhoea or chlamydia exert a powerful amplifying factor increasing the risk of HSIL above the risk with hrHPV alone. This pattern of disease in patients with warts is characteristic of a syndemic with potential increased risk of anal carcinoma in men because of rising rates of sexually-transmitted infections.
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