Screen all HIV-positive MSM for pre-cancerous anal cell changes, say Dutch investigators

Younger age and shorter duration of viral suppression are risk factors for the development of high-grade pre-cancerous anal lesions in HIV-positive men who have sex with men (MSM), investigators from the Netherlands report in AIDS.

They designed the study to identify demographic and HIV-related risk factors associated with the development of pre-cancerous anal lesions to target men who would benefit from high-resolution anoscopy (HRA). However, the prevalence of such lesions was so high that they recommend that all MSM living with HIV should undergo HRA.

“Of five demographic and seven HIV-related potential risk factors, only increasing age and living with suppressed viral load were significantly protective against HSIL [high-grade squamous intraepithelial lesions] vs. no SIL [squamous intraepithelial lesions],” write the authors. “Sensitivity analyses, including duration of cART [combination antiretroviral therapy] use instead of viral suppression, showed similar results.”

Glossary

lesions

Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.

squamous intraepithelial lesion (SIL)

This term is used to describe the detection of abnormal cells that have been ‘transformed’ by HPV into a possibly pre-cancerous state. According to the degree of cell change this will be called low-grade or high-grade SIL (LSIL or HSIL). If SIL is detected, a colposcopy will usually be ordered.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

sensitivity analysis

An additional analysis of data, also known as a “what–if” analysis, which indicates how robust the study’s results are. Specific assumptions or variables may be changed, to estimate the outcome in a range of scenarios.

sensitivity

When using a diagnostic test, the probability that a person who does have a medical condition will receive the correct test result (i.e. positive). 

HIV-positive MSM have an increased risk of developing anal cancer. Many treatment centres have established clinics to detect pre-cancerous lesions. An HRA-guided biopsy is considered the gold standard for the diagnosis of these lesions. However, HRA is uncomfortable and costly. It would, therefore, be beneficial to identify the risk factors for pre-cancerous anal lesions so that HRA screening can be appropriately targeted.

Investigators at three clinics in Amsterdam, therefore, designed a study involving 1678 HIV-positive MSM who underwent HRA between 2008 and 2015 (HRA screening was offered to all HIV-positive MSM attedning these clinics). The researchers conducted a series of analyses to see if specific demographic and HIV-related factors were associated with an increased risk of lesions, including HSIL.

The men had a mean age of 49 years and 96% were taking HIV therapy. The median duration of antiretroviral use was a little under eight years and 89% had an undetectable viral load. Median current CD4 cell count was 620 cells/mm3 and median nadir CD4 cell count was 220 cells/mm3. Approximately a fifth of participants had been previously diagnosed with an AIDS-defining illness.

After screening, 24% of men were diagnosed with low-grade pre-cancerous lesions and 30% with high-grade lesions.

Compared to men with no lesions, individuals with low-grade pre-cancerous cell changes were younger (p < 0.001), had higher numbers of recent sex partners (p = 0.016), had a lower number of years on HIV therapy (p < 0.001) and had fewer years of viral suppression (p < 0.001).

Comparison of men with HSIL versus those with no pre-cancerous cell changes identified two factors that were protective against the presence of high-grade pre-cancerous lesions: increasing age (aOR = 0.82; 95% CI, 0.70-0.94, p = 0.006) and increased number of years living with viral suppression (p = 0.009).

These factors remained unchanged in sensitivity analyses.

“Young HIV-positive MSM without viral suppression are statistically at highest risk of HSIL,” conclude the authors. “But given the high prevalence of HSIL among all virally suppressed men, we advise that all HIV-positive MSM should be screened for the presence of anal HSIL.”

References

Siegenbeek van Heukelom, ML et al. Risk factors for anal high-grade squamous intraepithelial lesions in HIV-positive MSM: is targeted screening possible? AIDS 31: 2295-2301, 2017.