A systematic review and meta-analysis of the association of human papilloma virus infections with ocular surface squamous neoplasia.

The incidence of Ocular Squamous Surface Neoplasia (OSSN) is increasing, particularly in populations with high HIV prevalence and higher solar irradiance. Human Papilloma Virus (HPV) is considered a precursor/co-factor to OSSN. We aimed to quantify the association between HPV and OSSN and analyse co-factors in this association, including geographical differences and pathology of the comparator group. We used the DerSimonian and Laird method to compute summary odds risk estimates in a random effects model. The I statistic was used to quantify heterogenicity. Subgroup analyses, sensitivity analyses and meta-regression were used to explore sources of heterogeneity. Twenty-one studies were included. The odds of HPV was significantly higher in OSSN lesions than benign lesions. The pooled odds ratio was 9.2 (95 % CI: 5.0-16.9) ((I = 56.1 % (95 % CI: 26 %-74 %)). In subgroup analysis, the odds ratio was lower in studies from African countries (with high HIV prevalences) and countries closer to the equator. The effect size was lower when ocular surface diseases such as pterygium were used as the comparator group rather than healthy tissues. We report a strong association between HPV and OSSN. The odds of HPV was 9.2 times higher in conjunctival cancers than benign tissues. This association was muted in African countries and countries closer to the equator, highlighting the role of UV radiation and HIV as co-factors in OSSN development. Muting of the association may also signal a role of pterygium as precursor lesions to OSSN, or that HPV may be involved in their development.