Demographics, clinical presentation and risk factors of ocular surface squamous neoplasia at a tertiary hospital, South Africa

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TL;DR

This prospective case-control study of 130 OSSN cases and 45 controls in Johannesburg found a median age of 44 years with equal gender distribution, and HIV was the strongest risk factor (74% prevalence in cases, OR 6.4, p<0.001). Clinically, leukoplakia, pigmentation, and gelatinous morphology were associated with OSSN, while fibrovascular morphology indicated benign lesions. The findings highlight the need to update OSSN demographic classifications by income level and emphasize the importance of HIV control in OSSN prevention.

Full summary

4,835 CHARS

**Background:** Ocular surface squamous neoplasia (OSSN) is the most common ocular surface tumor, encompassing conjunctival intra-epithelial neoplasia (CIN) and squamous cell carcinoma (SCC). Incidence varies from 0.03–1.9 per 100,000/year in high-income countries (HIC) to 1.6–3.4 per 100,000/year in sub-Saharan Africa. Traditionally, OSSN presents in older white males in HIC and younger black females in low- and middle-income countries (LMIC). Major risk factors include ultraviolet-B radiation and HIV infection. There is a paucity of data from South Africa. This study aimed to describe demographics, presenting features, and risk factors of OSSN at a tertiary eye hospital in Johannesburg.

**Methods:** An interventional prospective case-control study was conducted from December 2019 to February 2022. Patients with conjunctival masses suspicious for OSSN or symptomatic growths were enrolled. Exclusion criteria included age <18 years, pregnancy, previous surgery/chemotherapy in the presenting eye, masses >15 mm basal diameter, and heritable conditions predisposing to OSSN. An electronic questionnaire captured demographics, symptoms, and risk factors (HIV, ARV use, sun exposure, tobacco, ocular trauma, chronic inflammation, petroleum exposure). Slit-lamp examination documented clinical features, dimensions, morphology, and pigmentation (mild 0–33%, moderate 34–66%, severe 67–100%). Blood tests included HIV (with CD4 and viral load if reactive), hepatitis B/C serology, vitamin A levels, and CRP. All patients underwent biopsy; histology confirmed OSSN (CIN, carcinoma in situ [CiS], SCC) or benign lesions. Statistical analysis used STATA 17.0, with chi-square/Fisher's exact tests for categorical variables and logistic regression for odds ratios (OR) with 95% CI.

**Key Results:** 175 patients were recruited: 130 cases and 45 controls. Median age was 44 years (IQR 35–51) for cases vs 49 years (IQR 40–56) for controls (p=0.02). Gender distribution was equal (48% male, 52% female in cases). 98% of cases were Black African. Symptoms: pain was more common in cases (31% vs 13%, p=0.02), while reduced vision was more common in controls (29% vs 11%, p=0.004). Median symptom duration was 2 months (IQR 1–7) for cases vs 12 months (IQR 4–48) for controls (p<0.001). Clinical features significantly associated with OSSN: vascularisation (92% vs 78%, p=0.01), leukoplakia (52% vs 13%, p<0.001), pigmentation (55% vs 24%, p<0.001), and scleral fixation (15% vs 2%, p=0.027). Fibrovascular morphology was strongly associated with benign histology (69% vs 12%, p<0.001), while leukoplakic (61% vs 50%, p<0.001) and gelatinous (41% vs 42%, p=0.003) morphologies were associated with OSSN. Median surface area was 22 mm² (IQR 9–33.4) for cases vs 17.5 mm² (IQR 12.25–22) for controls (p=0.01). Histology: 82% of OSSN cases were CIN (CIN1 26%, CIN2 26%, CIN3 30%), 5% CiS, and 13% SCC. Controls were mostly pterygium (96%). HIV prevalence was 74% in cases vs 32% in controls (p<0.001). Among HIV-positive cases, median CD4 was 202 cells/µL (IQR 120–415) vs 595 cells/µL (IQR 270–722) in controls (p=0.003); median viral load was 2.86 log copies/mL (IQR 1–4.76) vs 1 log copies/mL (IQR 1–2.02) (p=0.004). ARV use duration was shorter in cases (median 29.5 months, IQR 11–95) vs controls (93 months, IQR 55–131) (p=0.02). Logistic regression: HIV (OR 6.4, 95% CI 3.0–13.7, p<0.001), leukoplakia (OR 6.9, 95% CI 2.7–17.5, p<0.001), gelatinous morphology (OR 4.2, 95% CI 1.6–11.5, p=0.005), pigmentation (OR 3.7, 95% CI 1.7–8.0, p=0.001), vascularisation (OR 3.1, 95% CI 1.2–7.9, p=0.02), pain (OR 2.9, 95% CI 1.1–7.4, p=0.03), and scleral fixation (OR 7.5, 95% CI 1.0–58.0, p=0.05) were associated with OSSN. Fibrovascular morphology was protective (OR 0.1, 95% CI 0.0–0.1, p<0.001). Sun exposure, tobacco, vitamin A levels, and hepatitis B/C were not significantly different.

**Clinical Implications:** This study updates the demographic classification of OSSN, showing that middle-income countries like South Africa have a younger cohort with no gender predilection, contrasting with the traditional dichotomy. The high prevalence of HIV (74%) and its strong association (OR 6.4) underscore the need for HIV screening and control in OSSN management. The predominance of CIN (82%) rather than SCC suggests earlier detection due to urban healthcare access, highlighting the importance of histopathological examination of all excised conjunctival masses, especially those clinically resembling pterygia (31% of suspected pterygia were OSSN). Pigmentation was common (55%) in this Black African cohort, emphasizing that OSSN should be considered in pigmented conjunctival lesions. The findings support integrating OSSN prevention into HIV care programs and call for further research on the roles of CD4, viral load, and HPV.