title: Pathophysiology of ocular surface squamous neoplasia.
abstract: The incidence of ocular surface squamous neoplasia (OSSN) is strongly associated with solar ultraviolet (UV) radiation, HIV and human papilloma virus (HPV). Africa has the highest incidence rates in the world. Most lesions occur at the limbus within the interpalpebral fissure particularly the nasal sector. The nasal limbus receives the highest intensity of sunlight. Limbal epithelial crypts are concentrated nasally and contain niches of limbal epithelial stem cells in the basal layer. It is possible that these are the progenitor cells in OSSN. OSSN arises in the basal epithelial cells spreading towards the surface which resembles the movement of corneo-limbal stem cell progeny before it later invades through the basement membrane below. UV radiation damages DNA producing pyrimidine dimers in the DNA chain. Specific CC → TT base pair dimer transformations of the p53 tumour-suppressor gene occur in OSSN allowing cells with damaged DNA past the G1-S cell cycle checkpoint. UV radiation also causes local and systemic photoimmunosuppression and reactivates latent viruses such as HPV. The E7 proteins of HPV promote proliferation of infected epithelial cells via the retinoblastoma gene while E6 proteins prevent the p53 tumour suppressor gene from effecting cell-cycle arrest of DNA-damaged and infected cells. Immunosuppression from UV radiation, HIV and vitamin A deficiency impairs tumour immune surveillance allowing survival of aberrant cells. Tumour growth and metastases are enhanced by; telomerase reactivation which increases the number of cell divisions a cell can undergo; vascular endothelial growth factor for angiogenesis and matrix metalloproteinases (MMPs) that destroy the intercellular matrix between cells. Despite these potential triggers, the disease is usually unilateral. It is unclear how HPV reaches the conjunctiva.
authors.affiliation: London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK; Department of Ophthalmology, University of Nairobi, P.O Box 19676-00202, Nairobi, Kenya. Electronic address: stephen.gichuhi@lshtm.ac.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gichuhi
authors.affiliation: UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK. Electronic address: s.ohnuma@ucl.ac.uk.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Ohnuma
authors.affiliation: UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK; St. Bartholomew's Hospital, W Smithfield, London EC1A 7BE, UK. Electronic address: m.sagoo@ucl.ac.uk.
authors.forename: Mandeep S
authors.initials: MS
authors.lastname: Sagoo
authors.affiliation: London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK; Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK. Electronic address: matthew.burton@lshtm.ac.uk.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Burton
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D005134:Eye Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D014943:Global Health; D006801:Humans; D015994:Incidence; D012307:Risk Factors
keywords: Cancer stem cells; HIV; HPV; Limbal stem cells; Ocular surface squamous neoplasia (OSSN); Pathophysiology; Ultraviolet radiation; p53