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Bridging the knowledge gap for ocular surface squamous


neoplasia: Africa and beyond
Ocular surface squamous neoplasia (OSSN) has emerged colleagues study appears higher than in other series;5,6 See Articles page e378

as an important manifestation of the HIV epidemic, what factors contribute to this finding remain to be
especially in sub-Saharan Africa.1 This region has not determined. The disease itself may carry an intrinsically
only gained the unenviable position of having the higher risk of recurrence in this population, and the
highest prevalence of OSSN, but patients with HIV limited availability of cryotherapy to the excision
tend to present with larger tumours and have a poorer margins may contribute as well.7 Gichuhi and colleagues
prognosis.2 The many factors that may contribute to point out that cryotherapy is not readily available in
these important features, such as co-existing human the region. However, even in developed countries,
papillomavirus infection, immunosuppression, delayed there are few prospective, randomised trials comparing
access to care, and ultraviolet radiation exposure, may the evolving combinations of surgical techniques and
also influence the response to therapy. adjuvant chemotherapeutic agents. The ideal approach
The care providers who are tasked with making to OSSN has not yet been defined in any population, and
evidence-based treatment decisions must often the wide range of reported outcomes mandates that
apply the results of studies performed in dissimilar randomised controlled trials are necessary to effectively
populations, then filter the therapeutic options through answer these questions. However, the available evidence
the narrow sieve of what is locally feasible. A previous supports the efficacy of cryotherapy in reducing
Cochrane review found a paucity of level I or II evidence recurrence after surgical excision. Opportunities
for the treatment of OSSN in patients with HIV.3 In for research and programme development include
The Lancet Global Health, Gichuhi and colleagues4 provide evaluating the cost-effectiveness of cryotherapy
helpful information to guide the care of individual compared to other adjuvants, such as 5-fluorouracil.
patients with OSSN, as well as informing those who may Adjuvant chemotherapy, either at the time of
influence allocation of resources and future research. surgery or postoperatively, has generally been found
Their study fills an important knowledge gap. A readily to decrease the risk of recurrence.8 Interferon alfa-2b,
available topical ophthalmic medication, 5-fluorouracil, mitomycin-C, and 5-fluorouracil have all been reported
was found to decrease the risk of recurrence after as efficacious. Interferon has gained popularity, both as
excision from 36·2% to 10·6% when compared to an empirical monotherapy, and as an additional therapy
placebo. At first glance, the specific regimen may be after surgical excision.9 However, several characteristics
questioned: why was cryotherapy not employed? Why of this medication limit its usefulness in sub-Saharan
study 5-fluorouracil when other topical agents, such as Africa. Cost is a paramount barrier; although the cost of
interferon alfa-2b and mitomycin-C, are more widely interferon medical therapy was found to be comparable
used among corneal specialists in developed nations? to surgery in one comparison,10 that study was based on
The answers to these questions highlight the importance Medicare-allowable charges for surgery and medication
of this study and others in delineating the best practices in the USA, which may not be directly applicable to
for OSSN in sub-Saharan Africa and beyond. developing regions. It is also important to recognise that
Recurrence of disease after surgical excision has been interferon is a protein that must be kept refrigerated
described in many regions; however, care must be to remain stable. This likely limits its usefulness in
taken when extrapolating the literature from North developing countries. Mitomycin would then seem to
American, European, and Australian populations. While be a rational alternative; while it has been surpassed in
the risk factors for recurrence have been reasonably well popularity by interferon, there are a multitude of studies
defined in those typically older, male, white patients, supporting the efficacy of this agent as monotherapy,
our understanding of OSSN in the frequently younger, or in addition to surgical excision. However,
HIV-positive patient from Africa is incomplete. At storage at room temperature is not recommended.
first glance, the recurrence reported in Gichuhi and 5-fluorouracil solution appears to remain stable without

www.thelancet.com/lancetgh Vol 4 June 2016 e347


Comment

refrigeration,11 and its general availability is encouraged 2 Nagaiah G, Stotler C, Orem J, Mwanda WO, Remick SC. Ocular surface
squamous neoplasia in patients with HIV infection in sub-Saharan Africa.
by its place on the World Health Organization’s list of Curr Opin Oncol 2010; 22: 437–42.
essential medicines. 3 Gichuhi S, Irlam JH. Interventions for squamous cell carcinoma of the
conjunctiva in HIV-infected individuals. Cochrane Database Syst Rev 2013;
Studies that specifically address reducing the risk of 2: CD005643.
recurrence in this population are welcome, and when 4 Gichuhi S, Macharia E, Kabiru J, et al. Topical fluorouracil after surgery for
ocular surface squamous neoplasia in Kenya: a randomised, double-blind,
viewed through the lens of pharmacoeconomics, placebo-controlled trial. Lancet Glob Health 2016; 4: e378–85.
provide vital guidance for health policy and the care 5 Sturges A, Butt AL, Lai JE, Chodosh J. Topical interferon or surgical excision
for the management of primary ocular surface squamous neoplasia.
of individual patients. Directions for future research Ophthalmology 2008; 115: 1297–302.
6 Nanji AA, Moon CS, Galor A, Sein J, Oellers P, Karp CL. Surgical versus
include additional comparative trials of the efficacy, medical treatment of ocular surface squamous neoplasia: a comparison of
safety, and cost-effectiveness of surgery compared to recurrences and complications. Ophthalmology 2014; 121: 994–1000.
7 Shields JA, Shields CL, De Potter P. Surgical management of conjunctival
topical chemotherapy alone, and continued efforts to tumors: the 1994 Lynn B McMahan Lecture. Arch Ophthalmol 1997;
improve access to effective care. 115: 808–15.
8 Nanji AA, Sayyad FE, Karp CL. Topical chemotherapy for ocular surface
squamous neoplasia. Curr Opin Ophthalmol 2013; 24: 336–42.
Donald U Stone 9 Adler E, Turner JR, Stone DU. Ocular surface squamous neoplasia: a survey
of changes in the standard of care from 2003 to 2012. Cornea 2013;
Wilmer Eye Institute of Johns Hopkins University, King Khaled Eye 32: 1558–61.
Specialist Hospital, PO Box 7191, Riyadh 11462, Saudi Arabia 10 Moon CS, Nanji AA, Galor A, McCollister KE, Karp CL. Surgical versus
dstone25@jhmi.edu medical treatment of ocular surface squamous neoplasia: a cost
comparison. Ophthalmology 2016; 123: 497–504.
I declare no competing interests. 11 Fuhrman LC, Godwin DA, Davis RA. Stability of 5-fluorouracil in an
Copyright © Stone. Open Access article distributed under the terms of CC BY. extemporaneously compounded ophthalmic solution. Int J Pharm Compd
2000; 4: 320–23.
1 Gichuhi S, Sagoo MS, Weiss HA, Burton MJ. Epidemiology of ocular surface
squamous neoplasia in Africa. Trop Med Int Health 2013; 18: 1424–43.

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