Genomic and Immunophenotypic Characteristics of Conjunctival Squamous Cell Carcinoma in a Sub-Saharan African Cohort Suggest a Role for Immune Checkpoint Inhibitors in Locally Advanced or Metastatic Patients

Abstract

PURPOSE Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with North America. The genomic and immunophenotypic characteristics of conjSCC is largely unknown. The long-term goal of this project is to evaluate the possible role of immune checkpoint inhibitor (ICI) therapy for this cancer in Sub-Saharan and developing nations. METHODS We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH, n=25) and USA (MDA, n=29). Genomic alterations were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas. A few patients from the MDA cohort with locally advanced and/or metastatic conjSCC were treated empirically with ICI and treatment outcomes were analyzed. RESULTS Solar elastosis was seen in 78% of ETH and 10% of MDA samples. Thicker tumors had higher density of CD8+ and CD3+ cells. HPV status was similar between the cohorts (ETH: 21%, MDA: 28%). The mean tumor mutation burden (TMB) was significantly higher in conjSCC (3.01/Mb, log10) and cutaneous SCC compared other SCC subtypes. ETH samples had higher TMB compared to MDA cohort (3.34 vs 2.73). Mutations in genes associated with ultraviolet light (UV) signature were most frequently encountered (SBS7b: 74% and SBS7a: 72%), with higher prevalence in ETH cohort, while SBS2 and SBS13 signatures were more common among MDA HPV+ conjSCCs. ICI therapy led to significant and dramatic clinical response in several patients with locally advanced conjSCC; these patients will be highlighted in the presentation. CONCLUSION Our findings suggest that UV exposure may play a role in conjSCC, with a higher prevalence in sub-Saharan Africa and that this cancer is associated with a high TMB. Of translational significance is the high TMB in conjSCC supports a possible role for ICI in the management of locally advanced or metastatic patients, particularly in sub-Saharan Africa, where this cancer is endemic and leads to significant morbidity and mortality. Future clinical trials should be designed using ICI in locally advanced and /or metastatic conjSCC patients in sub-Saharan Africa.