Ocular Surface Squamous Neoplasia in People Living With HIV: A Systematic Review of Treatment Outcomes in Low-Income and Middle-Income Countries

PURPOSE Ocular surface squamous neoplasia (OSSN) disproportionately affects people living with HIV (PLHIV) in low-income and middle-income countries (LICs and MICs), where the disease is more aggressive and resources for treatment are limited. This systematic review synthesizes evidence on treatment outcomes of OSSN in PLHIV across LICs and MICs. METHODS We searched PubMed/MEDLINE, Scopus, Embase, Cochrane CENTRAL, and Global Index Medicus for studies reporting treatment outcomes of histologically confirmed OSSN in PLHIV, conducted in LICs and MICs, with a minimum sample size of 11 patients. Study designs included randomized controlled trials (RCTs), cohorts, case-control studies, and case series. Title/abstract and full-text screening were performed using Rayyan. Data were extracted using a standardized form. Risk of bias was assessed using RoB-2 for the RCT and the Newcastle-Ottawa Scale for observational studies. The review was prospectively registered in PROSPERO (CRD420261371712). RESULTS Eight studies met inclusion criteria, comprising 1,576 patients from populations with HIV prevalence ranging from 41.5% to 98.8%, across eight countries in sub-Saharan Africa and South Asia. The single RCT demonstrated that topical fluorouracil 1% administered for four weeks after surgical excision substantially reduced one-year recurrence compared with placebo (11% v 36%; OR 0.21, 95% CI 0.07 to 0.63; number needed to treat = 4). Across observational studies, recurrence rates ranged from 3.2% to 24.2% by modality and follow-up. Radiotherapy achieved a favorable response in approximately 80% of patients with clinically evident disease. HIV-positive status was consistently associated with larger tumors, more advanced staging, and higher rates of orbital exenteration. In the pre-ART era, HIV-associated mortality reached 65% within 20 months, often preceding recurrence. Outcomes were seldom stratified by HIV status; antiretroviral therapy and CD4 data were rarely reported, precluding assessment of immunological modifiers. CONCLUSION Topical fluorouracil after surgical excision represents the only intervention supported by randomized evidence for OSSN in PLHIV in LICs and MICs, with a clinically meaningful reduction in recurrence. The broader evidence base is limited by observational designs, heterogeneous staging systems, short follow-up, and near-universal absence of ART-era data. Prospective trials integrating immunological parameters are urgently needed to guide treatment in this population.