Bridging the knowledge gap for ocular surface squamous neoplasia: Africa and beyond
Authors: Donald U Stone
Journal: The Lancet Global Health (2016)

Ocular surface squamous neoplasia (OSSN) has emerged as an important manifestation of the HIV epidemic, especially in sub-Saharan Africa.1Gichuhi S Sagoo MS Weiss HA Burton MJ Epidemiology of ocular surface squamous neoplasia in Africa.Trop Med Int Health. 2013; 18: 1424-1443Crossref PubMed Scopus (119) Google Scholar This region has not only gained the unenviable position of having the highest prevalence of OSSN, but patients with HIV tend to present with larger tumours and have a poorer prognosis.2Nagaiah G Stotler C Orem J Mwanda WO Remick SC Ocular surface squamous neoplasia in patients with HIV infection in sub-Saharan Africa.Curr Opin Oncol. 2010; 22: 437-442Crossref PubMed Scopus (39) Google Scholar The many factors that may contribute to these important features, such as co-existing human papillomavirus infection, immunosuppression, delayed access to care, and ultraviolet radiation exposure, may also influence the response to therapy. The care providers who are tasked with making evidence-based treatment decisions must often apply the results of studies performed in dissimilar populations, then filter the therapeutic options through the narrow sieve of what is locally feasible. A previous Cochrane review found a paucity of level I or II evidence for the treatment of OSSN in patients with HIV.3Gichuhi S Irlam JH Interventions for squamous cell carcinoma of the conjunctiva in HIV-infected individuals.Cochrane Database Syst Rev. 2013; 2 (CD005643)Google Scholar In The Lancet Global Health, Gichuhi and colleagues4Gichuhi S Macharia E Kabiru J et al.Topical fluorouracil after surgery for ocular surface squamous neoplasia in Kenya: a randomised, double-blind, placebo-controlled trial.Lancet Glob Health. 2016; 4: e378-e385Summary Full Text Full Text PDF PubMed Scopus (29) Google Scholar provide helpful information to guide the care of individual patients with OSSN, as well as informing those who may influence allocation of resources and future research. Their study fills an important knowledge gap. A readily available topical ophthalmic medication, 5-fluorouracil, was found to decrease the risk of recurrence after excision from 36·2% to 10·6% when compared to placebo. At first glance, the specific regimen may be questioned: why was cryotherapy not employed? Why study 5-fluorouracil when other topical agents, such as interferon alfa-2b and mitomycin-C, are more widely used among corneal specialists in developed nations? The answers to these questions highlight the importance of this study and others in delineating the best practices for OSSN in sub-Saharan Africa and beyond. Recurrence of disease after surgical excision has been described in many regions; however, care must be taken when extrapolating the literature from North American, European, and Australian populations. While the risk factors for recurrence have been reasonably well defined in those typically older, male, white patients, our understanding of OSSN in the frequently younger, HIV-positive patient from Africa is incomplete. At first glance, the recurrence reported in Gichuhi and colleagues study appears higher than in other series;5Sturges A Butt AL Lai JE Chodosh J Topical interferon or surgical excision for the management of primary ocular surface squamous neoplasia.Ophthalmology. 2008; 115: 1297-1302Summary Full Text Full Text PDF PubMed Scopus (74) Google Scholar, 6Nanji AA Moon CS Galor A Sein J Oellers P Karp CL Surgical versus medical treatment of ocular surface squamous neoplasia: a comparison of recurrences and complications.Ophthalmology. 2014; 121: 994-1000Summary Full Text Full Text PDF PubMed Scopus (78) Google Scholar what factors contribute to this finding remain to be determined. The disease itself may carry an intrinsically higher risk of recurrence in this population, and the limited availability of cryotherapy to the excision margins may contribute as well.7Shields JA Shields CL De Potter P Surgical management of conjunctival tumors: the 1994 Lynn B McMahan Lecture.Arch Ophthalmol. 1997; 115: 808-815Crossref PubMed Scopus (303) Google Scholar Gichuhi and colleagues point out that cryotherapy is not readily available in the region. However, even in developed countries, there are few prospective, randomised trials comparing the evolving combinations of surgical techniques and adjuvant chemotherapeutic agents. The ideal approach to OSSN has not yet been defined in any population, and the wide range of reported outcomes mandates that randomised controlled trials are necessary to effectively answer these questions. However, the available evidence supports the efficacy of cryotherapy in reducing recurrence after surgical excision. Opportunities for research and programme development include evaluating the cost-effectiveness of cryotherapy compared to other adjuvants, such as 5-fluorouracil. Adjuvant chemotherapy, either at the time of surgery or postoperatively, has generally been found to decrease the risk of recurrence.8Nanji AA Sayyad FE Karp CL Topical chemotherapy for ocular surface squamous neoplasia.Curr Opin Ophthalmol. 2013; 24: 336-342Crossref PubMed Scopus (62) Google Scholar Interferon alfa-2b, mitomycin-C, and 5-fluorouracil have all been reported as efficacious. Interferon has gained popularity, both as an empirical monotherapy, and as an additional therapy after surgical excision.9Adler E Turner JR Stone DU Ocular surface squamous neoplasia: a survey of changes in the standard of care from 2003 to 2012.Cornea. 2013; 32: 1558-1561Crossref PubMed Scopus (54) Google Scholar However, several characteristics of this medication limit its usefulness in sub-Saharan Africa. Cost is a paramount barrier; although the cost of interferon medical therapy was found to be comparable to surgery in one comparison,10Moon CS Nanji AA Galor A McCollister KE Karp CL Surgical versus medical treatment of ocular surface squamous neoplasia: a cost comparison.Ophthalmology. 2016; 123: 497-504Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar that study was based on Medicare-allowable charges for surgery and medication in the USA, which may not be directly applicable to developing regions. It is also important to recognise that interferon is a protein that must be kept refrigerated to remain stable. This likely limits its usefulness in developing countries. Mitomycin would then seem to be a rational alternative; while it has been surpassed in popularity by interferon, there are a multitude of studies supporting the efficacy of this agent as monotherapy, or in addition to surgical excision. However, storage at room temperature is not recommended. 5-fluorouracil solution appears to remain stable without refrigeration,11Fuhrman LC Godwin DA Davis RA Stability of 5-fluorouracil in an extemporaneously compounded ophthalmic solution.Int J Pharm Compd. 2000; 4: 320-323PubMed Google Scholar and its general availability is encouraged by its place on the World Health Organization's list of essential medicines. Studies that specifically address reducing the risk of recurrence in this population are welcome, and when viewed through the lens of pharmacoeconomics, provide vital guidance for health policy and the care of individual patients. Directions for future research include additional comparative trials of the efficacy, safety, and cost-effectiveness of surgery compared to topical chemotherapy alone, and continued efforts to improve access to effective care. I declare no competing interests. Topical fluorouracil after surgery for ocular surface squamous neoplasia in Kenya: a randomised, double-blind, placebo-controlled trialTopical fluorouracil after surgery substantially reduced recurrence of OSSN, was well-tolerated, and its use recommended. Full-Text PDF Open Access