Decentralized homologous recombination deficiency (HRD) testing in advanced high-grade serous ovarian carcinoma: real-world implementation and molecular profiling from Morocco

Abstract Background Homologous Recombination Deficiency (HRD) testing guides poly (ADP-ribose) polymerase inhibitor (PARPi) therapy in high-grade serous ovarian carcinoma (HGSOC). Centralized commercial assays pose logistical and financial barriers in low- and middle-income countries (LMICs). This study evaluated the pathological validation, clinical implementation, molecular landscape, and feasibility of a decentralized HRD testing platform in North Africa. Materials and methods This real-world cohort study enrolled 215 advanced HGSOC patients at the National Institute of Oncology in Rabat, Morocco (March 2024–March 2026). Following strict histopathological selection (tumor cellularity ≥ 20%, necrosis < 30%), local genomic profiling utilized an in-house next-generation sequencing (NGS) pipeline (Oncomine Comprehensive Assay Plus) on formalin-fixed paraffin-embedded (FFPE) tumor tissue. HRD positivity was defined by a genomic instability metric (GIM) score ≥ 16. Objective pre-analytical metrics were defined to categorize testing failures. Results Pre-analytical quality control failed in 57/215 samples (26.5%). DNA degradation ( n = 40, 70.2% of failures) was driven by real-world pre-analytical variability in decentralized workflows, while low DNA yield ( n = 17, 29.8% of failures) was linked to small core needle biopsies with low tumor cellularity or extensive stromal fibrosis. Among 158 evaluable patients, 87 (55.1%) were HRD-positive; 57.5% (50/87) harbored BRCA1/2 mutations and 42.5% (37/87) were BRCA wild-type. HRD prevalence significantly associated with age ( p = 0.017), peaking at 69.4% (50–59 years) and dropping to 32.1% (≥ 70 years). Confrontation of TP53 NGS data with immunohistochemical (IHC) reflex testing on NGS wild-type cases ( n = 27) identified 19 cases with aberrant p53 staining patterns, raising the total rate of p53 abnormalities to 94.9% (150/158). Average turnaround time was three weeks. One test represented 37.1% of the country’s annual Gross Domestic Product (GDP) per capita and over 400% of the monthly minimum wage. Conclusions Local, decentralized testing is clinically viable in resource-limited settings. Addressing pre-analytical tissue processing quality and conducting formal health-economic evaluations are essential to ensuring sustainable access to precision oncology across LMICs.