Telomerase promoter mutations in human immunodeficiency virus-related conjunctiva neoplasia

BACKGROUND: Squamous cell carcinoma (SCC) of the conjunctiva is a common cancer in Africa mainly associated with solar ultraviolet (UV) exposure and human immunodeficiency virus (HIV) infection. We analyzed the role of HIV on the occurrence of telomerase reverse transcriptase (TERT) promoter mutations among a cohort of conjunctiva neoplasia Ugandan patients. METHODS: Telomerase reverse transcriptase promoter mutations were searched in 72 conjunctiva neoplasia cases, comprising SCC and intraepithelial neoplasia grade 1–3 (CIN1–3), as well as in 53 conjunctiva normal tissues and in 24 HIV-related Kaposi sarcoma. RESULTS: The average prevalence of TERT promoter mutations in conjunctiva neoplasia was 31.9%. The mutation rates were significantly higher in HIV-positive (31.8% of CIN1 and CIN2, 46.2% of CIN3 and SCC,) than HIV-negative patients (22.2% of CIN1 and CIN2, 13.3% of CIN3 and SCC). Such mutations were rarely identified among HIV-positive conjunctiva controls (3.6%) and never in Kaposi sarcoma lesions. The most frequent variations were the hot spots − 124G>A and − 146G>A and tandem transitions − 124_125GG>AA and − 138_139GG>AA. CONCLUSIONS: Telomerase reverse transcriptase promoter mutations are early events in conjunctival neoplasia and could be used for timely diagnosis of conjunctiva tumours. The high frequency of UV-signatures in HIV-positive conjunctiva lesions suggests an additive effect of the virus to UV-related mutagenesis.