Should anal Pap smears be introduced for people with HIV?

A systematic review of research studies has concluded that there is not yet enough evidence to indicate that anal Papanicolau (Pap) smears should be used routinely to detect pre-cancerous cells in people with HIV. The review’s results were published in the 15^th July edition of Clinical Infectious Diseases.

Anal cancer is more common in gay men than in the general population, and is linked to HIV infection in both men and women. As the incidence of anal cancer has increased over the last 30 years, doctors are interested in developing simple methods to detect early signs of pre-cancerous changes or ‘anal intraepithelial neoplasia’ in the anuses of people with HIV. They hope that picking up pre-cancer in the anus may enable earlier treatment, reducing the risk of illness and death.

Anal cancer is a very similar disease to cervical cancer in women. Both cancers are caused by strains of the human papilloma virus, progressing through stages of neoplasia until cancer develops. They are both more common in people with HIV.

Guidelines recommend that HIV-positive women undergo cervical Pap smears every six months in order to look for pre-cancerous cells. Consequently, doctors are now interested in establishing whether Pap smears should be introduced to look for pre-cancerous cells in the anus.

A group of doctors from Houston and San Francisco in the United States carried out a systematic review of all 181 research papers published on anal Pap smears in HIV-positive people between July 1996 and July 2005. Sixty-three of these papers described original research studies in sufficient detail to be included in their analysis, which set out to establish whether screening would have a significant impact on the outcomes of people with HIV.

There are no randomised trials examining the outcomes of anal Pap smears. However, by collating the available evidence, the doctors confirmed that people with HIV were at an increased risk of developing pre-cancerous cells in the anus and anal cancer. This was particularly evident in HIV-positive gay men.

Despite this, however, other aspects related to Pap screening were less clear, highlighting the need for further research before routine anal Pap smears can be introduced.

Firstly, there is no evidence to indicate whether individuals who have had Pap smears have better outcomes than those who do not. “Although anal Pap smear screening is not being performed on a large enough scale to conduct ecologic studies, future anal Pap smear screening efficacy studies may instead focus on comparing different types and intensity of screening methods,” the doctors write.

The analysis revealed that anal Pap smears were about as accurate an Pap smears of the cervix in women in detecting pre-cancerous cells, especially when combined with high-resolution anoscopy. This is a technique where a small telescope is inserted into the anus and a small piece of anal tissue is taken for analysis under the microscope.

However, the effectiveness of the various treatments for pre-cancerous anal cells is still uncertain. At present, possible options include surgical removal, treatment with imiquimod (Aldara), fluorouracil (Efadix), cidofovir (Vistide) or interferon, and vaccines against human papillomavirus, although more research is needed to establish their effectiveness.

The available studies disagree on the effect of antiretroviral therapy on pre-cancerous cells in the anus. While three of the five studies analysed found no effect of anti-HIV treatment, the remaining two found a positive effect.

What's more, there is still uncertainty surrounding the rate at which pre-cancer progresses to anal cancer in patients with HIV.

Finally, the doctors estimated that routine introduction of anal Pap smears would involve screening and follow-up of large numbers of patients. Although this is likely to have a similar cost-effectiveness to established screening programmes, its introduction would require substantial training of staff, and improvements in adherence of patients to treatment protocols.

“The operating characteristics of the anal Pap smear have been evaluated and are of modest accuracy, with accuracy similar to that of the cervical Pap smear,” write the doctors.

“Until a consensus regarding anal Pap smear screening can be reached, a heightened awareness of anal cancer among HIV-infected individuals is warranted,” they warn. “Further research is needed to identify improved methods for preventing, diagnosing, and treating anal dysplasia.”