Anal cancer is a neglected disease.Whether through shame and embarrassment, or self-diagnosis of a haemorrhoid, late presentations are not uncommon and have an overall five-year survival of only 65%. It is an important disease which is potentially preventable but, whether the measure is research time and money, media coverage or the allocation of a coloured ribbon, anal cancer has not received the attention it deserves.Before discussing who gets anal cancer, why they get it, how we might prevent it and the efforts being taken to do so, the anatomy and terminology need to be established and understood.

• Gentle traction placed on the buttocks will reveal perianal lesions (those falling within 5 cm of the anal opening) however anal canal lesions will be visualised incompletely or not at all by means of this manoeuvre. This is vitally important to appreciate because accurate description of location has direct clinical relevance. Anal canal cancers are more aggressive and require chemoradiation, while perianal cancers behave more like skin cancers and wide excision is usually appropriate.
• The anal canal has three zones – colorectal, transformation and lower canal. The transformation zone, centred on the dentate line, is where the glandular epithelium of the rectum meets the squamous epithelium of the lower canal, and is analogous to that in the cervix. It may encompass several centimetres, have poorly demarcated margins and is characterised by ongoing squamous metaplasia and constant replacement of glandular epithelium.

The transformation zone is where most anal canal cancers arise.

Who gets anal cancer?

While it is a rare disease in the general community (1–1.5/100,000), several sub-populations have very high rates of anal cancer:

• HIV-positive men who have sex with men
• Other HIV-positive individuals (male and female)
• HIV-negative men who have sex with men
• Organ transplant recipients
• Women with a history of HPV-related vulval/vaginal/ cervical cancer or pre-cancer

About 95% of anal cancers are caused by HPV and the great majority of these are caused by HPV 16. HPV is a sexually transmitted infection and anal intercourse an efficient means of HPV transmission; however, anal intercourse is not a prerequisite for anal HPV infection.Anal HPV infection is common in both sexes (whether or not anal intercourse is reported) but most anal infections are transient.Anal cancer is a rare outcome associated with persistence of the virus and with other co-factors, such as smoking and immunosuppression.

Is prevention of anal cancer possible?

VaccinationAustralia was the first country in the world to commence an organised HPV vaccination program, starting with girls and young women in 2007 and extending to school-aged boys in 2013.While vaccine efficacy for the prevention of anal cancer is anticipated to be similar to that for cervical cancer, proof of it will take longer to demonstrate. Unlike cervical cancer, the incidence of anal cancer continues to increase into old age and therefore the benefits of vaccination may take decades to become apparent.Screening for pre-cancerDigital anorectal examination (DARE) is currently recommended to detect the earliest anal cancers. In addition, some centres screen for anal pre-cancer using a model based on the multiple similarities which exist between cervical and anal cancer, namely the same virus infecting the same type of transformation zone, leading to development of the same precancerous, high-grade squamous intraepithelial lesion (HSIL) which can be detected cytologically.These commonalities translate, in the setting of anal cancer screening, to a process involving anal cytology, possibly anal HPV testing and high-resolution anoscopy (akin to colposcopy), followed by biopsy.Despite these correlations between cervical and anal HPV infection and the plausibility of similar screening protocols being applicable in both settings, a screening program for anal cancer has not been as widely implemented as may have been expected.Why is this?-Near-universality of HPV infection in men who have sex with men limits the effectiveness of HPV testing in triage.-Not enough is known about the natural history of anal HSIL and it is likely to differ in significant ways from cervical cancer. In gay men, for example, high-grade lesions appear to be quite common and a proportion may regress without treatment.-There is no accepted treatment for patients with biopsy-diagnosed anal HSIL. While the entire transformation zone of the cervix can be excised with few sequelae, this is not possible in the anal canal and there is no reliable evidence for any other interventions currently used.

Summary

At this stage neither HPV testing or anal cytology can be recommended as routine screening procedures for anal cancer and pre-cancer.Until certain key questions are answered, at-risk patients should be identified, reviewed annually by DARE and managed accordingly.Vaccination is worth offering to those in at-risk groups and is safe and effective in the immunosuppressed. - General Practice Pathology is a regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.