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Editors Selection IGR 25-3

Glaucoma and Systemic Diseases: Could HPV infection be a risk factor for glaucoma?

Comment by Louis Pasquale on:

127218 Human Papillomavirus Infection Is Associated with Increased Risk of Glaucoma: Evidence in an Electronic Health Record Study, Liao WC; Su YJ; Li YF et al., Ophthalmology, 2025; 132: 1161-1168

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There are over 200 types of human papillomavirus (HPV), and infection is highly prevalent among young adults. Women are more likely to be diagnosed with infection because of an emphasis on cervical cancer screening and the complications associated with HPV infections; yet, many infections go undetected. Theoretically, HPV could lead to both open-angle glaucoma (OAG) and angle-closure glaucoma (ACG) by triggering neuroinflammation.

Using a case (HPV+) – control (HPV-) study design in a database of 120 million US participants, Liao et al. excluded prevalent glaucoma at baseline to assess the relationship between HPV infection and OAG, ACG, or both types of glaucoma combined. They appropriately used propensity matching to reduce confounding and formed a female-predominant study population (~62%) of approximately 900,000, with a mean age of 28 years at baseline. The investigators used ICD coding to determine all exposures, outcomes, and covariates. They found that HPV infection was associated with a ~30 to ~60% increased risk of glaucoma (OAG, ACG, or both), depending on the models used. There was no association between HPV infection and secondary glaucoma. A myriad of sensitivity and stratification analyses affirmed the positive associations. They also found that certain comorbidities (for example, diabetes (DM)) exacerbated this association.

The investigators discuss surveillance bias as a possible cause of their finding, but they don’t ensure comparable ophthalmic care for their cases and controls (who were young). The claim that conditions like DM could compound the association between HPV infection and glaucoma is not supported by the p-for-interaction test. For example, the increased hazard ratio for HPV (+) DM (+) [case] vs HPV (-) DM (-) [control] may simply reflect the marginal impact of DM on glaucoma risk. More study is needed to explore the relationship between HPV infection and glaucoma.

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