Risk factors of melanoma among people living with HIV in South Africa, 2004 - 2021
MOTHOSOLA R. 1,2, WRIGHT C. 3, MUCHENGETI M. 2,4, METEKOUA C. 4,5,9, TOMBE - NYAHUMA T. 4, MOHLALA M. 4, MASHELE S. 4,6,7, ROHNER E. 5, RUFFIEUX Y. 5, DHOKOTERA T. 6,7,8, AYENI P. 6, KIPO D. 6, BOHLIUS J. 6,7, KUONZA L. 1,2, MWANSA-KAMBAFILWE J. 2,4
1 South African Field Epidemiology Program, Johannesburg, South Africa; 2 University of the Witwatersrand, Johannesburg, South Africa; 3 Environment and Health Research Unit, South African Medical Research Council, and Department of Geography, Geoinformatics and Meteorology, University of Pretoria, Pretoria, South Africa; 4 National Cancer Registry, Johannesburg, South Africa; 5 Institute of Social and Preventative Medicine, University of Bern, Bern, Switzerland; 6 Epidemiology and Public Health Department, Swiss Tropical and Public Health Institute,, Allschwil, Switzerland; 7 University of Basel , Basel, Switzerland; 8 Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland; 9 Graduates School for Health Sciences, University of Bern, Bern, Switzerland
Background: People living with HIV (PLWH) have unique immunological and clinical vulnerabilities that increase their susceptibility to secondary health risks. In the antiretroviral therapy (ART) era, infection-unrelated cancers such as melanoma have emerged as an important public health concern. However, melanoma risk among PLWH and the extent to which immunosuppression influences this risk remain understudied, particularly in sub-Saharan Africa. Chronic immune dysregulation, reduced immune surveillance, and persistent inflammation may contribute to melanoma susceptibility as life expectancy increases among PLWH. Despite South Africa (SA) having the world’s largest HIV epidemic, little is known about melanoma epidemiology among PLWH.
Objective: To identify risk factors associated with melanoma skin cancer among PLWH in South Africa from 2004 to 2021.
Methods: This study used data from the South African HIV Cancer Match study, a nationwide cohort of PLWH, created through probabilistic record linkage of HIV-related laboratory records from the National Health Laboratory Service and cancer records from the National Cancer Registry from 2004 to 2021. Cohort entry was defined as the date of the first HIV-related laboratory record. Participants were followed from cohort entry until melanoma diagnosis or end of follow-up, whichever occurred first. Hazard ratios (HRs) for melanoma were estimated using Royston–Parmar flexible parametric survival models, adjusting for sex, race, baseline age, CD4 counts, settlement type, latitude of residence, and calendar period.
Results: Among 9,415,806 PLWH, 123 were diagnosed with melanoma, with a crude incidence rate of 0.22 per 100,000 person-years (95% confidence interval [CI] = 0.16–0.26). Melanoma incidence decreased between 2010 and 2015, with a 48% lower risk (adjusted hazard ratio [aHR] = 0.52; 95% CI = 0.33–0.80) compared with 2004–2009. Females had a 67% lower risk of developing melanoma compared to males (aHR = 0.33; 95% CI = 0.22–0.49), and White PLWH had 13 times higher melanoma risk than Black PLWH (aHR = 13.25; 95% CI = 8.02–21.87). Melanoma risk increased steeply with age (≥60 years vs <30 years; aHR = 20.90; 95% CI = 9.36–46.70). PLWH with CD4 counts of 200–349 cells/µL and those with CD4 counts ≥500 cells/µL had 2.6 times higher risk of being diagnosed with melanoma than those with <100 cells/µL (aHR = 2.62; 95% CI = 1.25–5.48 and aHR = 2.68; 1.20–5.96, respectively). PLWH living within latitudes 30°S to 34°S had a 29-fold higher risk of melanoma (aHR=28.95; 95% CI=2.65–315.98) than those living within a latitude of <25°S. We found no association between rural or urban settlement type and melanoma risk.
Conclusion: The association between higher CD4 counts and melanoma risk reflects immune reconstitution and prolonged survival following ART initiation, increasing opportunities for melanoma detection rather than a direct causal effect of immune recovery. Residence further south, indicative of higher seasonal ultraviolet radiation exposure, was associated with an increased risk of melanoma. These findings highlight priority groups for targeted skin cancer surveillance within HIV care, including older PLWH, patients with immune reconstitution on ART, and those residing in southern regions of SA.