Abstract

Conjunctival squamous cell carcinoma (CoSCC) is rare compared to cutaneous SCC and the incidence varies based on UV exposure, prevalence of ocular inflammatory diseases and immune status, with higher incidence closer to the equator. To determine if the predisposing factors may differ based on geographic location, we compared CoSCC cohort from Ethiopia (EC n=25) to an US cancer center (USC n=29) by Whole Exome Sequencing. Call for hotspot oncogenic mutations were set at allele frequency>5%; q-value<0.1 and 10% false discovery rate. While the mutational profile of CoSCC was most similar to SCCs of head & neck, lung and skin, mutations in HLAB, CTLA4, HNF1A, IRS2, GNAQ and KNSTRN were unique to CoSCC. TP53 and IRS2/GNAQ mutations were common in well and poorly differentiated tumors, respectively. The following differences were noted between the 2 cohorts: (i) hotspot mutation frequency per sample- higher in EC, mean 9.44 vs 7.76 in USC (p=0.03); (ii) type of mutations- relatively increased incidence of T>G transversions in USC compared to EC; (iii) commonly mutated genes after HLA-B and TP53- CDKN2A, CTLA4, HNF1A in EC and IRS2, HNF1A, CTLA4 and GNAQ in USC; (iv) degree of subconjunctival solar elastosis- higher in EC (56%, compared to 10% in USC) and associated with higher frequency of C>T transitions (UV signature) as well as TP53 and CDKN2A mutations; (v) high-risk human papilloma virus positivity in USC (27%) compared to EC (20%) and associated with lower frequency of TP53 (q=0.009) and CDKN2A (q=0.03) mutations; and (vi) frequent ?1% PD-L1 expression in USC (69%, compared to EC: 52%). However, considering only the number of nucleotides included in cancer hotspot mutation set, the overall mutation rate was similar in EC vs. USC and HPV+ vs. HPV- cohorts. Thus, the risk factors for CoSCC differ based on various exogenous and endogenous factors; therefore, preventive and curative approaches should be tailored accordingly, including immunotherapy for advanced CoSCC.

Financial Disclosure:
No current or relevant financial relationships exist.