Abstract Body

HIV-positive women are at increased risk of human papillomavirus (HPV) infection and progression to invasive cervical cancer (ICC). HIV and HPV epidemics and access to cervical cancer screening vary between regions. We compared ICC risk in women on combination antiretroviral therapy (ART) in Asia-Pacific, North America, Latin America, Southern Africa, and Europe.

We included cohorts participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord. We included HIV-positive women aged ≥ 16 years who started ART after cohort enrollment from 1996 onwards. We used flexible parametric survival models with region-specific baseline hazards adjusted for time-updated CD4 cell counts, age, and year of ART start to compare regional ICC rates. We excluded Asia-Pacific from multivariable analyses due to small sample size. We present incidence rates and adjusted hazard ratios (aHR) with 95% confidence intervals (CI).

We included 65,726 women from 55 countries. Median age at ART start was 35 years and similar across regions. Median CD4 cell count (cells/µL) at ART start was 115 in Southern Africa, 146 in Asia-Pacific, 179 in Latin America, and 241 in Europe and North America. Median follow-up time was 3.9 years (interquartile range 1.5-7.3). During 323,224 person-years (pys) 390 women developed ICC. Incidence rate per 100,000 pys was highest in Southern Africa (497, 95%CI 429-577) followed by Latin America (152, 95%CI 97-238), North America (76, 95%CI 48-119), Europe (71, 95%CI 62-83) and Asia-Pacific (42, 95%CI 6-297). With the exception of Southern Africa regional ICC risks decreased with time since ART start (see Figure). Adjusted hazard ratios comparing Europe with other regions at 2 and 5 years were 8.9 (95%CI 6.0-13.3) and 12.4 (95%CI 7.8-20.0), respectively, for Southern Africa, and 2.1 (95%CI 0.8-5.0) and 2.2 (95%CI 1.2-4.2), respectively, for Latin America. No difference was observed between North America and Europe.

HIV-positive women in Southern Africa and Latin America had a markedly higher ICC risk than women from North America and Europe, and rates did not decline with time on ART in Southern Africa. These regional differences were not explained by differences in CD4 counts, age, or year of starting ART, but could be explained by a higher prevalence and incidence of HPV infection and limited access to effective cervical cancer screening.