The Role of Viruses in the Development of Ocular Surface Squamous Neoplasia and Pterygium

Main Article Content

mitra akbari


Human Immunodeficiency Virus, Human Papillomavirus, Ocular Surface Squamous Neoplasia, Pterygium


High prevalence of infections with human papillomavirus (HPV) and human immunodeficiency virus (HIV) is reportedly associated with an increased frequency of ocular surface squamous neoplasia (OSSN). The present review article aimed to evaluate the relationship between viruses such as HIV/HPV with OSSN and HPV with other possible related viruses with a pterygium. HIV infection increases the frequency and severity of OSSN, although the documented report on the involvement of HPV is inconclusive. The research findings evaluating both mucosal and cutaneous subtypes of HPV infection suggested an association only between the cutaneous subtype and the increased risk of OSSN. Despite uncertainties on the function of oncogenic viruses in the pterygium development, the present literature found a clear disparity. The available data elucidate a potential of these viruses in the pathogenesis of pterygium, at least in a certain group of patients.

Abstract 171 | PDF Downloads 151 XML Downloads 18 HTML Downloads 14


1. Coroneo M. Ultraviolet radiation and the anterior eye. Eye Contact Lens Sci Clin Pr. 2011;214–224.
2. Alizadeh Y, Akbari M, Moghadam RS, Dourandeesh M, Moravej Z. Comparison of pterygium recurrence with and without using postsurgical topical cyclosporine A 0.05%: A randomized clinical trial. J Curr Ophthalmol 2022; 34:208-15.
3. Akbari M, Elmi R. Herpes simplex virus and human papillomavirus coinfections in hyperimmunoglobulin E syndrome presenting as a conjunctival mass lesion. Case reports in medicine. 2017;Article ID 1650841.
4. Akbari M, Soltani-Moghadam R, Elmi R, Kazemnejad E. Comparison of free conjunctival autograft versus amniotic membrane transplantation for pterygium surgery. J Curr Ophthalmol. 2017; 29(4): 282-286.
5. Spitzer MS, Batumba NH, Chirambo T, Bartz‐Schmidt, K. U Kayange P, Kalua K, Szurman P. Ocular surface squamous neoplasia as the first apparent manifestation of HIV infection in Malawi. Clin Experiment Ophthalmol. 2008; 36(5):422–5.
6. Rathi SG, Kapoor AG, Kaliki S. Ocular surface squamous neoplasia in HIV-infected patients: current perspectives. HIV/AIDS (Auckland, NZ). 10 AD; 33.
7. Soong HK, Feil SH, Elner VM, Elner S, Flint A. Conjunctival mucoepidermoid carcinoma in a young HIV-infected man. Am J Ophthalmol. 1999; 128(5):640–3.
8. Liu T, Liu Y, Xie L, He X, Bai J. Progress in the pathogenesis of pterygium. Curr Eye Res. 2013; 38(12):1191–7.
9. Gothai S, Muniandy K, Mohd Esa N, Subbiah S, Arulselvan P. Anticancer potential of Alternanthera sessilis extract on HT-29 human colon cancer cells. Asian Pac J Trop Biomed. 2018;8: 394–402.
10. Piras F, Moore PS, Ugalde J, Perra MT, Scarpa A, Sirigu P. Detection of human papillomavirus DNA in pterygia from different geographical regions. Br J Ophthalmol. 2003; 87(7): 864–6.
11. Piecyk Sidor M, Polz Dacewicz M, Zagórski Z, Żarnowski T. Occurrence of human papillomavirus in pterygia. Acta Ophthalmol. 2009; 87(8): 890–5.
12. Karcioglu ZA and Issa TM: Human papilloma virus in neoplastic and non-neoplastic conditions of the external eye. Br J Ophthalmol 81: 595-598, 1997.
13. Saegusa M, Takano Y, Hashimura M, Okayasu I and Shiga J: HPV type 16 in conjunctival and junctional papilloma, dysplasia, and squamous cell carcinoma. J Clin Pathol. 48: 1106-1110, 1995.
14. Kiire CA and Dhillon B: The aetiology and associations of conjunctival intraepithelial neoplasia. Br J Ophthalmol. 90: 109-113, 2006.
15. Chui J, Di Girolamo N, Wakefield D & Coroneo MT (2008): The pathogenesis of pterygium: current concepts and their therapeutic implications. Ocul Surf . 6: 24–43.
16. Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/ AIDS compared with immunosuppressed transplant recipients: a meta- analysis. Lancet. 2007; 370:59–67.
17. Porges Y, Groisman GM. Prevalence of HIV with conjunctival squamous cell neoplasia in an African provincial hospital. Cornea. 2003; 22(1): 1–4.
18. Oellers P, Karp CL, Kao AA, Abdelaziz A, Matthews J, Sheth A, et al. Subclinical Ocular Surface Squamous Neoplasia in Pterygia. Invest Ophthalmol Vis Sci. 2012; 53(14): 4222–4228.
19. McCarty CA, Fu CL, Taylor HR. Epidemiology of pterygium in Victoria, Australia. Br J Ophthalmol. 2000; 83(4): 289–92.
20. Al Bdour MD, Al Latayfeh MTM. Risk factors for pterygium in an adult Jordanian population. Acta Ophthalmol Scand. 2007; 82(1): 64–7.
21. H Carreira, F Coutinho, C Carrilho and N Lunet. HIV and HPV infections and ocular surface squamous neoplasia: systematic review and meta-analysis. BRITISH JOURNAL OF CANCER 2013:109; 1981-1988.
22. Govardhanan Nagaiah, Christy Stotler, Jackson Orem, Walter O. Mwanda, and Scot C. Remick Ocular surface squamous neoplasia in patients with HIV infection in sub-Saharan Africa. Curr Opin Oncol. 2010 September; 22(5): 437–442.
23. Nkomazana O, Tshitswana D. Ocular complications of HIV infection in sub-Sahara Africa. Curr HIV/AIDS Rep. 2008; 5(3): 120–125.
24. Gichuhi S, Sagoo MS, Weiss HA, Burton MJ. Epidemiology of ocular surface squamous neoplasia in Africa. Trop Med Int Health. 2013; 18(12): 1424–1443.
25. Guech-Ongey M, Engels E, Goedert J, Biggar R, Mbulaiteye S. Elevated risk for squamous cell carcinoma of the conjunctiva among adults with AIDS in the United States. Int J Cancer. 2008; 122 (11): 2590–2593.
26. Makupa II, Swai B, Makupa WU, White VA, Lewallen S. Clinical factors associated with malignancy and HIV status in patients with ocular surface squamous neoplasia at Kilimanjaro Christian Medical Centre, Tanzania. Br J Ophthalmol. 2012; 96(4): 482–484.
27. Osahon AI, Ukponmwan CU, Uhunm wangho OM. Prevalence of HIV seropositivity among patients with squamous cell carcinoma of the conjunctiva. Asian Pac J Trop Biomed. 2011; 1(2): 150–153.
28. Mahomed A, Chetty R. Human immunodeficiency virus infection, Bcl-2, p53 protein, and Ki-67 analysis in ocular surface squamous neoplasia. Arch Ophthalmol. 2002; 120(5): 554–558.
29. Shields CL, Ramasubramanian A, Mellen PL, Shields JA. Conjunctival squamous cell carcinoma arising in immunosuppressed patients (organ transplant, human immunodeficiency virus infection). Ophthalmology 2011; 118(11): 2133–2137.
30. Uthaithammarat, L Kasetsuwan, N Chongpison, Y Kasetsuwan, P Reinprayoon, U Nilyanimit, P Poovorawan Y. Lack of HPV in pterygium with no evidence of autoinoculation and the role of cytokines in pterygium with dry eye. Sci Rep. 2021; 11(1):1–10.
31. Shahraki T, Arabi A, Feizi S. Pterygium: an update on pathophysiology, clinical features, and management. Ther Adv Ophthalmol. 2021; 13:25.
32. Gichuhi S, Sagoo M, Weiss H, Burton M. Epidemiology of ocular surface squamous neoplasia in Africa. Trop Med Int Heal 18. 2013; 18:1424–43.
33. Chalkia AK, Tseliou M, Bontzos G, Tsakalis, N. G Liakopoulos DA, Blazaki S, Detorakis ET. Association between HPV detection in swab samples and tissue specimens and ophthalmic pterygium recurrence. Graefe’s Arch Clin Exp Ophthalmol. 2021; 259(10): 3077–82.
34. Rykov SO, Usenko KO, Mogilevskyy S, Ziablitsev S V, Denisiuk LE. Relationship of the recurrence after pterygium surgery with the presence of HSV, EBV, CMV, HPV, and BRAFV600E mutation. J Ophthalmol. 2019; 1:3–8.
35. Detorakis ET, Drakonaki EE and Spandidos DA. Molecular genetic alterations and viral presence in ophthalmic pterygium. Int J Mol Med 2000; 6: 35–41.
36. Detorakis ET, Sourvinos G and Spandidos DA. Detection of herpes simplex virus and human papilloma virus in ophthalmic pterygium. Cornea 2001; 20: 164–167.
37. Spandidos D, Xinarianos G, Ergazaki M, et al. The presence of herpesviruses in pterygium. Int J Oncol 1994; 5: 749–752.
38. Chen YF, Hsiao CH, Ngan KW, et al. Herpes simplex virus and pterygium in Taiwan. Cornea 2008; 27: 311–313.
39. Hamed-Azzam S, Edison N, Briscoe D, et al. Identification of human papillomavirus in pterygium. Acta Ophthalmol 2016; 94: e195– e197.
40. Tsai Y-Y, Chang C-C, Chiang C-C, et al. HPV infection and p53 inactivation in pterygium. Mol Vis 2009; 15: 1092–1097.
41. Otlu B, Emre S, Turkcuoglu P, et al. Investigation of human papillomavirus and Epstein-Barr virus DNAs in pterygium tissue. Eur J Ophthalmol 2009; 19: 175–179.
42. Chen K, Hsu W, Cheng C, Li Y. Lack of human papillomavirus in pterygium of Chinese patients from Taiwan. Br J Ophthalmol. 2003; 87:1046–8.
43. Sjö N, von Buchwald C, Prause J, Norrild B, Vinding T, Heegaard S. Human papillomavirus and pterygium. Is the virus a risk factor? Br J Ophthalmol. 2007; 91:1016–8.
44. Takamura Y, Kubo E, Tsuzuki S, Akagi Y. Detection of human papillomavirus in pterygium and conjunctival papilloma by hybrid capture II and PCR assays. Eye. 2008; 22:1442–5.
45. Mackay I. Real-time PCR in the microbiology laboratory. Clin Microbiol Infect. 2004; 10:190–212.
46. Guthoff R, Marx A, Stroebel P. No evidence for a pathogenic role of human papillomavirus infection in ocular surface squamous neoplasia in Germany. Curr Eye Res. 2009; 34:666–71.
47. Tsai Y, Chang C, Chiang C, Yeh K, Chen P, Chang C. HPV infection and p53 inactivation in pterygium. Mol Vis. 2009; 15:1092–7.
48. Bottalico D, Chen Z, Dunne A, Ostoloza J, McKinney S, Sun C. The oral cavity contains abundant known and novel human papilloma- viruses from the Beta papillomavirus and Gamma papillomavirus genera. J Infect Dis. 2011; 204:787–92.
49. McKelvie P, Daniell M, McNab A, Loughnan M, Santamaria J. Squamous cell carcinoma of the conjunctiva: A series of 26 cases. Br J Ophthalmol. 2002; 86:168–73.
50. Köhler A, Gottschling M, Manning K, Lehmann M, Schulz E, Krüger Corcoran D, Stockfleth E, et al. Genomic characterization of ten novel cutaneous human papillomaviruses from keratotic lesions of immunosuppressed patients. J Gen Virol. 2011; 1585–94.
51. Tornesello M, Duraturo M, Waddell K, Biryahwaho B, Downing R, Balinandi S, et al. Evaluating the role of human papillomaviruses in conjunctival neoplasia. Br J Cancer. 2006;(94): 446–9.
52. Chauhan S, Sen S, Sharma A, Dar L, Kashyap S, Kumar P, et al. Human papillomavirus: A predictor of better survival in ocular surface squamous neoplasia patients. Br J Ophthalmol. 2012; 96:1517–21.
53. De Koning M, Waddell K, Magyezi J, Purdie K, Proby C. 38) Genital and cutaneous human papillomavirus (HPV) types in relation to conjunctival squamous cell neoplasia: A case-control study in Uganda. Infect Agent Cancer. 2008; 3(12).
54. Koss L. Cytologic and histologic manifestations of human papillomavirus infection of the uterine cervix. Cancer Detect Prev. 1990; 14:461–4.
55. Sámano-Hernández L. Presence of Human Papilloma Virus in pterygium and its association with an apoptotic proteome profile. Investig Ophthalmol Vis Sci April. 2014;
56. Joanna R, Renata Z, Witold P, Małgorzata S, Bernaczyk, P Chyczewski L. The evaluation of human papillomavirus and p53 gene mutation in benign and malignant conjunctiva and eyelid lesions. Folia Histochem Cytobiol. 2010; 48:530–3.