Early diagnosis is key

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Post by Neil McKellar-Stewart28 Nov 2013

In any year, 78 in 100,000 HIV-positive gay men will be diagnosed with anal cancer. Some have suggested there is a ‘perfect storm’ of factors that have come together within this group to produce these relatively high rates: increasing age; persistent HPV infection (and reinfection from receptive anal sex with multiple partners); immune suppression caused by ongoing HIV persistence; a higher prevalence of high-risk HPV types; faster rates of progression from low-grade pre-cancerous lesions to true cancers; and very high levels of tobacco smoking (1).

Anal cancer is almost always associated with persistent high-risk type human papillomavirus (HPV) infection. There are over 100 different HPV genotypes; however, HPV16 is most often associated with anal cancer.

Prevention can proceed along three lines.

Primary prevention is possible by the vaccination recently licensed for use in Australia. A recently published randomised trial proved that vaccination of young HIV-negative gay men will prevent anal cancer precursors. In 2013, free vaccination of school-aged boys began in Australia. However, this will not work for older men living with HIV, in whom HPV infection has a firm hold.

Secondary prevention consists of screening for HPV infection and identifying the precancerous lesions associated with HPV infection and treating them. But there are issues.

In the ongoing Study of the Prevention of Anal Cancer (SPANC), based in Sydney, high-grade anal intraepithelial neoplasia (HGAIN) is found in around 40% of gay men with HIV (2,3); however, the progression rate to outright cancer is very low. Maybe only one in 400-600 per year will progress, therefore routine screening would identify large numbers of men with HGAIN but many of whom will not progress to outright anal cancer. Plus, it is now believed that high rates of HGAIN spontaneously regress (4).

As well, there are no agreed treatment modalities for treating HGAIN. Recurrence rates after treatment are very high, and it has yet to be demonstrated that treating HGAIN leads to reduced incidence of anal cancer at a population level.

Collecting representative cells (cytology) from the convoluted surface of the anus requires time and skill. Similarly, high-resolution anoscopy (HRA) to study the interior surface of the anus requires specialised equipment, time (perhaps 30 minutes per examination) and well-trained expert staff. HRA facilities are only available in a few of the major capital cities.

For secondary prevention to progress, much more effective ways will need to be developed to both screen for and treat HGAIN.

This leaves tertiary prevention, i.e., detecting and effectively treating cancer in its early stage.

Prognosis worsens as the size of the cancer progresses, so if identified when the cancer is less than 1 cm there is good prognosis for effective treatment.

Good evidence from the Anal Cancer Examination (ACE) study shows that annual digital anorectal examination (DARE) may be effective in identifying many anal cancers early so that they can be effectively treated.

The risk of anal cancer is small but significant for PLHIV. The message is that screening and early treatment require more attention from both PLHIV and their clinicians.

  1. 1.Machalek DA et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012 May;13(5):487-500
  2. 2.Machalek DA et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012 May;13(5):487-500.
  3. 3.Gaisa M, Sigel K, Hand J, Goldstone S. High rates of anal dysplasia in HIV-infected men who have sex with men, women, and heterosexual men. AIDS. 2013 online Sep 25.
  4. 4.Tong WW et al. Progression to and spontaneous regression of high-grade anal squamous intraepithelial lesions in HIV-infected and uninfected men. AIDS. 2013 Sep 10;27(14):2233-43