Incidence of anal cancer has already peaked among HIV-positive gay men; reductions can be achieved with expanded ART coverage and screening

The incidence of anal cancer among HIV-positive gay men peaked in 2009 and will decline substantially by 2030, even with current levels of antiretroviral therapy (ART) coverage and no cancer-screening programme, Swiss investigators report in AIDS. Further significant reductions would be achieved with 100% treatment coverage and various screening strategies. These would be more effective at preventing cases of anal cancer than screening for cervical cancer among women in the general population.

“This is the first study to predict the incidence of anal cancer in HIV-positive MSM [men who have sex with men] over many years taking into account cART [combination antiretroviral therapy] coverage and individual CD4 cell trajectories,” comment the authors. “Our modeling study predicts substantial reductions in anal cancer incidence in MSM in the next 15 years, even in the absence of screening and without further increases in cART coverage. The model also predicts that the introduction of yearly anal Pap screening or anoscopy screening, or CD4 cell guided anoscopy screening would reduce anal cancer incidence further.”

Anal cancer is caused by oncogenic (cancer-causing) strains of human papillomavirus (HPV), especially HPV-16. Incidence of anal cancer among HIV-negative gay men is 5 cases per 100,000 person-years, about five times higher than the rate observed in the general population. Anal cancer is even more common among HIV-positive gay men, with an estimated incidence between 78 and 168 cases per 100,000 person-years.

Known risk factors for anal cancer in HIV-positive gay men are persistent infection with high-risk HPV strains, smoking and a low CD4 cell count.

ART increases CD4 cell count and research conducted in North America and the Netherlands suggests its widespread use has already been associated with a plateauing of incidence of anal cancer among gay men with HIV.

Screening for anal cancer can be done in two ways. Cytology uses a PAP smear, where a cell sample is taken and examined under a microscope for pre-cancerous or cancerous changes.

High-resolution anoscopy with histology is carried out by inserting a tube into the anus and examining the tissue of the anal canal with a bright light and a magnifying device, after applying a solution containing acetic acid to the anal tissue in order to make abnormal cells easier to see.

Both methods can detect pre-cancerous anal cell changes and lesions so that appropriate and early treatment can be provided. However, there is controversy about the usefulness of such screening and its cost-effectiveness.

Investigators from the Swiss HIV Cohort Study wanted a clearer understanding of the incidence of anal cancer among their gay male patients, especially the relationship between cART coverage and various screening strategies.

They developed a model plotting incidence of the malignancy over 50 years between 1980 and 2030. Variables included in the model included cART coverage, CD4 cell count trajectory and screening and treatment for pre-cancerous lesions.

The records of 6411 gay men who received care between 1983 and 2015 were used to plot changes in CD4 cell count and cART coverage.

The median nadir CD4 cell count increased from 229 cells/mm³ in the period between 1980 and 1989 to 394 cells/mm³ between 2010 and 2015. Potent HIV treatment only became available in 1996, and by 2010-15 coverage had reached 83%.

Modelling showed that incidence of anal cancer peaked in 2009 at 82 cases per 100,000 person-years. Incidence levelled off between 2010-15. In a scenario where the proportion of patients taking cART remained stable at 83%, the incidence of anal cancer would fall by 2030 to 59 cases per 100,000 person-years, a decline of 28% from the 2009 peak.

When the authors modelled 100% cART coverage from 2016 onwards, they found that incidence would drop to 52 cases per 100,000 person-years, a reduction of 11% relative to the baseline scenario where cART coverage remained stable.

Universal treatment coverage with annual anoscopy followed by treatment when appropriate, decreased incidence to 33 cases per 100,000 person-years, a reduction of 44% relative to the baseline scenario. Yearly anal cytology was associated with an incidence of 38 cases per 100,000 person-years in 2030, a 35% reduction compared to the baseline model. Finally, CD4 cell-guided anoscopy was associated with incidence of anal cancer in 2030 of 51 cases 100,000 person-years, a reduction of 13% compared to the baseline model.

The authors calculated that 384 gay men would need to undergo anal cytology each year for 15 years to prevent one case of anal cancer. A screening strategy using anoscopy would require 313 men to be screened for 15 years to prevent one case of the malignancy. With CD4-guided screening, 242 gay men would need to be screened for 15 years to prevent one case of anal cancer, but the percentage of cases prevented would be lower compared to the other strategies.

These screening strategies would be as effective as those currently in place for other cancers. For example, it has been estimated that 1800 women in the general population would need to be screened every five years to prevent a single case of cervical cancer.

“Clearly, further research on the cost-effectiveness and acceptability of different strategies for anal cancer screening is warranted,” conclude the authors. “In the meantime, increasing cART coverage further in MSM and the HIV-positive population in general remains an important priority in Switzerland and globally.”