A routine anal screening programme for people living with HIV was associated with a significant reduction in the incidence of anal cancer, investigators from Germans Trias i Pujol University Hospital, Badalona, Catalonia, Spain and the department of medicine, Autonomous University of Barcelona, report. Individuals were offered anal check-ups with appropriate treatment for pre-cancerous lesions. Comparison between those participating in the screening programme and those who declined screening showed that regular check-ups (followed by treatment when needed) reduced the risk of anal cancer by 83%.
“To the best of our knowledge this is the first cohort analysis that demonstrates an impact in the incidence of invasive anal squamous cell carcinoma of such a screening strategy,” comment the authors.
Dr William Bonnez of the University of Rochester, New York, described the study as “important” in an accompanying editorial. But he also suggests that the results are not definitive, especially because the investigators may not have fully adjusted their analysis to take account of differences between the screening and non-screening groups. Rates of anal cancer – usually caused by persistent infection with high risk strains of human papillomavirus (HPV) – are much higher among people with HIV (especially HIV-positive gay and other men who have sex with men) compared to the general population.
Cervical cancer is also usually caused by HPV infection. The use of routine cytological screening to detect pre-cancerous cell changes has resulted in massive reductions in rates of cervical cancer.
A randomised clinical trial is currently underway in the US (the ANCHOR study) to determine the benefits and cost-efficiency of routine cytological check-ups to prevent anal cancer. Its results are expected in 2022.
However, a number of HIV treatment centres have introduced their own screening programmes. Starting in 2005, a team of clinicians led by Dr Boris Revollo at the Hospital Germans Trias I Pujol, Barcelona, offered their patients annual anal screening. Their study population included 3,111 adult HIV-positive individuals. The structured screening programme involved an annual cytological check-up for pre-cancerous cell changes. When these were detected, individuals underwent high resolution anoscopy and biopsy. Pre-cancerous anal lesions were aggressively treated with infrared coagulation or surgery.
In the present study, Revollo and his colleagues compared incidence of anal cancer between individuals who underwent screening and those who declined to participate in the programme.
Data were collected on age, duration of HIV infection, HIV risk group, current and nadir CD4 cell count and viral load.
The median duration of follow-up was a little under five years. Overall, 54% of their patients participated in the screening programme.
At baseline, 44% of these individuals had normal anal cytology and 7% had high-grade pre-cancerous cell changes. During follow-up, high-grade cell changes were detected in a further 17% of individuals. A total of 1288 high-resolution anoscopies were performed, 744 biopsies were taken and 142 high-grade pre-cancerous lesions were diagnosed. Ten cases of anal cancer were diagnosed during the 12 years of the programme. Two of these cases were in individuals enrolled in the screening programme. The other eight cases were in people who did not have annual anal cytology tests.
In every case, the person diagnosed with anal cancer had previously had a CD4 cell count below 150 (though at the time of diagnosis, half of them had a CD4 cell count above 350).
The two cases detected in the screening group involved a fast evolving and aggressive form of cancer. Both individuals carried the high-risk HPV16 strain and diagnosis of pre-cancerous lesions was complicated by the presence of haemorrhoids. Both individuals responded to therapy and were alive at the end of follow-up.
The cumulative incidence of anal cancer was 0.1% in the screening group (0.2% among gay men/men who sex with men, 0% in other risk groups) compared to 0.6% among individuals who were not screened (0.3% in gay men/men who have sex with men and 0.7% in women).
Incidence rates were 21.9 per 100,000 person-years and 107 per 100,000 person-years, respectively, a statistically significant difference (p = 0.027) in favour of the screening group.
Analysis of the entire cohort showed that the only risk factor associated with a diagnosis of anal cancer was time since diagnosis with HIV (a longer duration, HR = 1.14; 95% CI, 1.02-1.26).
Taking in account potential confounders and adjusting for possible risk factors, the investigators found a highly significant protective effect in favour of screening, which reduced the risk of diagnosis with anal cancer by 83% (HR = 0.17; 95% CI, 0.03-0.86). There was also some evidence that screening had a survival benefit: both of the men in the screening group who were diagnosed with anal cancer were alive at the end of follow-up. In contrast, five of the eight people who did not undergo screening died. The authors conclude that these results support “the continued interpretation of such programs while results from randomised clinical trials and analyses involving larger cohorts are eagerly awaited to clarify the efficacy of this strategy.”
In his editorial, Bonnez hails the study as “an important, if initial attempt at demonstrating the usefulness of anal screening for the prevent of invasive anal squamous cell carcinoma in HIV subjects.” But he questions whether the investigators’ analyses were able to fully account for differences between their two groups – the benefits of screening may not have been as large as suggested.
However, he concludes that the study “takes us a little closer to an appropriate, validated and cost-effective approach for anal cancer prevention in those living with HIV, but the remaining ground to cover to enter public health policy could still be extensive and disputed.”
Abstract
Background: The efficacy of screening programs to prevent anal cancer in persons with human immunodeficiency virus 1 (HIV-1) is unclear.
Methods: To examine the impact of a screening program to detect anal cancer precursors on the incidence of cases of invasive anal squamous-cell carcinoma (IASCC) in persons with HIV-1, we performed a single-center, retrospective analysis of a prospective cohort of outpatients with HIV-1 attending a reference HIV unit from January 2005 onward. All participants were invited to participate in a continued structured screening program for anal cancer prevention. We estimated the incidence of IASCC and performed a comparative analysis between subjects enrolled in the screening program (screening group) and those who declined to participate (nonscreening group). To reduce any selection bias, a propensity score analysis was applied.
Results: We included 3111 persons with HIV-1 (1596 men-who-have-sex-with-men [MSM], 888 men-who-have-sex-with-women [MSW], 627 women; mean age, 41 years), with a median follow-up of 4.7 years (14 595 patient-years of follow-up); 1691 (54%) participated in the screening program. Ten patients were diagnosed with IASCC: 2 (MSM) in the screening group and 8 (4 MSM, 2 MSW, and 2 women) in the nonscreening group. The incidence rates of IASCC were 21.9 (95% confidence interval [CI], 2.7–70.3) and 107.0 (95% CI, 46.2–202.0) per 100 000 person-years, respectively. After a propensity score adjustment, the difference was significant in favor of the screening group (hazard ratio, 0.17; 95% CI, .03–.86).
Conclusions: The number of cases of IASCC was significantly lower in persons with HIV engaged in an anal cytology screening program. These results should be validated in a randomized clinical trial.
Authors
Boris Revollo, Sebastián Videla, Josep M Llibre, Roger Paredes, Marta Piñol, Francesc García-Cuyàs, Arelly Ornelas, Jordi Puig, David Parés, Javier Corral, Bonaventura Clotet, Guillem Sirera
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