People with HIV diagnosed with anal cancer have poorer survival after diagnosis, especially women, and survival rates for all people diagnosed with anal cancer have not improved significantly over the past 20 years, a US study published in Lancet HIV reports.
Anal cancer is a rare cancer, caused by cancer-causing strains of human papillomavirus. The HPV vaccine that protects against cervical cancer also protects against anal cancer, but HPV is widespread among people with HIV and living with HIV greatly increases the risk of developing anal cancer. One study found that the risk of anal cancer was 39 times higher among gay and bisexual men with HIV compared to the rest of the US population.
Like all cancers, the risk of anal cancer may increase with age. As the population of older people with HIV grows due to improved survival on antiretroviral treatment, the incidence of anal cancer might be expected to grow. But what’s unclear is how living with HIV affects survival after a diagnosis of anal cancer and whether age, sex, race or ethnicity affect survival among people with HIV.
Dr Jaimie Shing of the National Cancer Institute and colleagues at state cancer registries investigated anal cancer survival in 13 US states in people aged 20-79 who were diagnosed with anal cancer between 2001 and 2019. They identified 24,486 people diagnosed with anal cancer reported during the study period. Of these, 2662 were living with HIV.
People with HIV and others diagnosed with anal cancer differed in several respects. People with HIV were more often male (85% vs 33%), aged under 60 (87% vs 49%), non-Hispanic Black (37% vs 12%) or Hispanic (21% vs 10%) and less often non-Hispanic White (37% vs 74%). People with HIV were more often diagnosed with non-squamous cell carcinoma than others (96% vs 84%) and when the cancer was at a localised stage (52% vs 47%). There was no substantial difference in receipt of treatment or surgery for anal cancer by HIV status, but people with HIV were somewhat less likely to undergo chemotherapy, perhaps because of the greater frequency of localised cancers.
During the follow-up period, 43% of people with HIV and 35% of others with anal cancer died from any cause. After adjusting for confounding factors, all-cause mortality was two-and-a-half times higher in women with HIV compared to women without HIV and 35% higher in men with HIV compared with men without HIV. Considering only deaths due to anal cancer, mortality was 52% higher in women with HIV compared to women without HIV. There was no difference in mortality between men with and without HIV.
Although five-year anal-cancer-specific survival in men with HIV was higher than in men without HIV (80% vs 72%), the reverse was true in women with HIV (74% vs 80%). Anal cancer mortality was significantly higher in people diagnosed with adenocarcinoma, which develops in the cells deeper in the anus near the rectum. This cancer was less common in people with HIV.
Comparing five-year anal cancer survival in people with HIV by the period of diagnosis, the researchers found that although there was a trend towards improved survival in people diagnosed between 2015 and 2019 compared with those diagnosed between 2001 and 2004, the reduction in the risk of death was not statistically significant.
Among people with HIV, all-cause and anal cancer mortality was significantly higher among people who acquired HIV through injecting drug use compared to those who acquired HIV through sex between men and women. There was no difference in anal cancer mortality by race or ethnicity but all-cause mortality was slightly higher (19% higher risk of death) in non-Hispanic Black people with HIV compared to non-Hispanic White people.
The study investigators say that increased awareness among healthcare providers of the need to screen gay and bisexual men with HIV for anal cancer may explain the difference in anal cancer mortality between men and women with HIV. They say that more data on the effects of anal cancer screening and treatment of high-grade squamous intraepithelial lesions on anal cancer mortality will be helpful.
In a second study, Dr Cameron Haas and colleagues at the National Cancer Institute reported on the risk of death after being diagnosed with high-grade (severe) squamous intraepithelial lesions (AIN grade III) in the Journal of the National Cancer Institute. AIN grade III means that severely abnormal cells can be detected in the anus. It is a precursor to the development of anal cancer.
Most people who are diagnosed with AIN grade III will not develop anal cancer and in some cases, AIN grade III goes away without treatment. But in most cases, doctors will advise treatment of AIN grade III with surgery, laser treatment or imiquimod cream to remove the abnormal cells.
Looking at cancer registries in 11 US states between 1996 and 2016, Dr Haas and colleagues found that rates of AIN grade III increased by 14% a year in men with HIV compared to 6% in men without HIV. When the rate of change was analysed by time period, AIN grade III diagnoses in men did not increase between 1996 and 2004 but did increase significantly from 2005 to 2019. Rates increased by 15% in women with HIV and 6% a year in women with HIV but there was no evidence of an accelerating trend over time.
In the five years following a diagnosis of AIN grade III, 1.3% of men with HIV who did not have an AIDS diagnosis developed squamous cell carcinoma of the anus. No women with HIV who did not have an AIDS diagnosis developed anal cancer. Among those with an AIDS diagnosis, 3.7% of men and 3.4% of men developed anal cancer after being diagnosed with AIN grade III.
The researchers say that the increased rate of AIN grade III is probably a consequence of increased screening and that people with a prior diagnosis of AIDS should be prioritised for screening.
Shing JZ et al. Survival by sex and HIV status in patients with anal cancer in the USA between 2001 and 2019: a retrospective cohort study. Lancet HIV 11: e31-41, 2024.
Haas CB et al. Severe anal intraepithelial neoplasia trends and subsequent invasive anal cancer in the United States. Journal of the National Cancer Institute, 116 (1): 97-104, 2024 (open access).