Conjunctival Papilloma Treatment & Management
- Author: Hon-Vu Q Duong, MD; Chief Editor: Hampton Roy, Sr, MD more...
Observation and patient reassurance are indicated for squamous cell papillomas. These lesions may regress spontaneously over time. Seeding may follow excision, resulting in multiple new lesions. For limbal papillomas, excision is indicated to rule out neoplastic changes.
Cryotherapy is indicated for squamous cell papillomas. Less scarring occurs, and the recurrence rate is low. It is not indicated for limbal papillomas because this procedure does not distinguish between benign papillomas and malignant papillomas. The double-freeze-thaw method is preferred and appears to be the most effective technique.
Dinitrochlorobenzene (DNCB): Petrelli et al demonstrated success with DNCB in the treatment of recurrent conjunctival papillomas. This treatment modality is reserved for cases when surgical excision, cryoablation, and other treatment modalities have failed. The patient is sensitized to DNCB. Once sensitized, DNCB is applied directly to the papilloma. The mechanism for this treatment appears to be the delayed hypersensitivity reaction causing the tumor to regress; however, the exact mechanism is unknown.
Interferon is an adjunct therapy to surgical excision of recurrent and multiple lesions. Alpha interferon is given intramuscularly (daily for 1 mo, 2-3 times/wk for the next 6 mo, then tapered off). Lass et al indicated both nonrecurrence and recurrence of conjunctival lesions. However, those recurring lesions tend to be less severe in clinical presentation. Because of its antiviral and antiproliferative properties, this form of therapy is designed to suppress tumor cells; it is not curative. Additionally, topical interferon alpha-2b has been shown to be an effective adjunct therapy for small-to-medium size lesions but not for large lesions without surgical debulking. Topical interferon alpha-2b can be utilized as an adjunctive therapy for recurring conjunctival papilloma.[9, 10] More recently, topical alpha-2b interferons have shown to be successful in treating not only primary conjunctival papilloma but also conjunctival intraepithelial neoplasia.
Mitomycin-C is an adjunct therapy to surgical excision. Mitomycin-C is indicated for recalcitrant conjunctival papillomas or those refractive to past multiple treatments. Hawkins et al reported complete regression of conjunctival papilloma 9 months after surgical excision followed by intraoperative mitomycin-C application. Mitomycin-C (0.3 mg/mL) is applied via a cellulose sponge to the involved area(s) after surgical excision. The sponge is held in place for 3 minutes. The treated area is irrigated copiously with normal saline after mitomycin-C application. Complications include symblepharon, corneal edema, corneal perforation, iritis, cataract, and glaucoma.
Oral cimetidine (Tagamet): Although commonly used to treat peptic ulcer disease, cimetidine has shown to be effective in the treatment of recalcitrant conjunctival papilloma. Shields et al demonstrated dramatic tumor regression with nearly complete resolution in an 11-year-old boy treated with cimetidine. Chang et al indicated that oral cimetidine can be used as an initial treatment modality in cases where the lesion is quite large and recalcitrant. Apart from its antagonistic effect on H2 receptors, cimetidine has been found to enhance the immune system by inhibiting suppressor T-cell function and augmenting delayed-type hypersensitivity responses.
Carbon dioxide (CO2) laser: Schachat et al and Jackson et al reported this treatment modality to be safe and most effective.[15, 16] It is indicated for recalcitrant conjunctival papillomas. The procedure is performed easily. This procedure allows for precise tissue excision with minimal blood loss and trauma to tissue. Rapid healing of tissues occurs without significant scarring, edema, or symblepharon formation. Recurrence is low, resulting from the destruction of viral particles and papillomatous epithelial cells. Gentamicin ointment twice a day for 7-10 days is prescribed postoperatively to allow proper healing and reepithelialization.
Other treatment modalities include electrodesiccation, topical acids, topical cantharidin, and intralesional bleomycin.
Excision is indicated for squamous cell and limbal papillomas.
Performing an excisional biopsy is recommended for adults to rule out premalignancy changes.
In the pediatric population, performing an excisional biopsy is less clear. This is a surgical procedure requiring general anesthesia. To justify the risk of anesthesia, this procedure is indicated in cases where the lesion is causing significant symptoms, (ie, cosmetically disfiguring, has not regressed, appearance of new lesion).
An excisional biopsy is preferred to an incisional biopsy whenever possible.
A consult with a general pathologist or, ideally, an ophthalmic pathologist is recommended.
Peck N, Lucarelli MJ, Yao M, et al. Human papillomavirus 6a lesions of the lower eyelid and genitalia. Ophthal Plast Reconstr Surg. 2006 Jul-Aug. 22(4):311-3. [Medline].
Sjo NC, Buchwald CV, Cassonnet P, et al. Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma. Types and frequencies in a large series. Br J Ophthalmol. 2006 Dec 13. [Medline].
Minchiotti S, Masucci L, Serapiao Dos Santos M, Perrella E, Graffeo R, Lambiase A. Conjunctival papilloma and human papillomavirus: identification of HPV types by PCR. Eur J Ophthalmol. 2006 May-Jun. 16(3):473-7. [Medline].
Egbert JE, Kersten RC. Female genital tract papillomavirus in conjunctival papillomas of infancy. Am J Ophthalmol. 1997 Apr. 123(4):551-2. [Medline].
Lauer SA. Recurrent conjunctival papilloma causing nasolacrimal duct obstruction. Am J Ophthalmol. 1990 Nov 15. 110(5):580-1. [Medline].
Migliori ME, Putterman AM. Recurrent conjunctival papilloma causing nasolacrimal duct obstruction. Am J Ophthalmol. 1990 Jul 15. 110(1):17-22. [Medline].
Petrelli R, Cotlier E, Robins S, Stoessel K. Dinitrochlorobenzene immunotherapy of recurrent squamous papilloma of the conjunctiva. Ophthalmology. 1981 Dec. 88(12):1221-5. [Medline].
Lass JH, Foster CS, Grove AS, et al. Interferon-alpha therapy of recurrent conjunctival papillomas. Am J Ophthalmol. 1987 Mar 15. 103(3 Pt 1):294-301. [Medline].
Muralidhar R, Sudan R, Bajaj MS, Sharma V. Topical interferon alpha-2b as an adjunctive therapy in recurrent conjunctival papilloma. Int Ophthalmol. 2009 Feb. 29(1):61-2. [Medline].
de Keizer RJ, de Wolff-Rouendaal D. Topical alpha-interferon in recurrent conjunctival papilloma. Acta Ophthalmol Scand. 2003 Apr. 81(2):193-6. [Medline].
Falco LA, Gruosso PJ, Skolnick K, Bejar L. Topical interferon alpha 2 beta therapy in the management of conjunctival papilloma. Optometry. 2007 Apr. 78(4):162-6. [Medline].
Hawkins AS, Yu J, Hamming NA, Rubenstein JB. Treatment of recurrent conjunctival papillomatosis with mitomycin C. Am J Ophthalmol. 1999 Nov. 128(5):638-40. [Medline].
Shields CL, Lally MR, Singh AD, et al. Oral cimetidine (Tagamet) for recalcitrant, diffuse conjunctival papillomatosis. Am J Ophthalmol. 1999 Sep. 128(3):362-4. [Medline].
Chang SW, Huang ZL. Oral cimetidine adjuvant therapy for recalcitrant, diffuse conjunctival papillomatosis. Cornea. 2006 Jul. 25(6):687-90. [Medline].
Schachat A, Iliff WJ, Kashima HK. Carbon dioxide laser therapy of recurrent squamous papilloma of the conjunctiva. Ophthalmic Surg. 1982 Nov. 13(11):916-8. [Medline].
Jackson WB, Beraja R, Codere F. Laser therapy of conjunctival papillomas. Can J Ophthalmol. 1987 Feb. 22(1):45-7. [Medline].
Bailey RN, Guethlein ME. Diagnosis and management of conjunctival papillomas. J Am Optom Assoc. 1990 May. 61(5):405-12. [Medline].
Bosniak SL, Novick NL, Sachs ME. Treatment of recurrent squamous papillomata of the conjunctiva by carbon dioxide laser vaporization. Ophthalmology. 1986 Aug. 93(8):1078-82. [Medline].
Buggage RR, Smith JA, Shen D, Chan CC. Conjunctival papillomas caused by human papillomavirus type 33. Arch Ophthalmol. 2002 Feb. 120(2):202-4. [Medline].
Campbell RJ. Tumors of the eyelids, conjunctiva, and cornea. Garner A, Klintworth GK, eds. Pathobiology of Ocular Disease - A Dynamic Approach. Marcel Dekker Inc; 1994. 1367-8(chap 46).
Chang T, Chapman B, Heathcote JG. Inverted mucoepidermoid papilloma of the conjunctiva. Can J Ophthalmol. 1993 Jun. 28(4):184-6. [Medline].
Chiemchaisri Y, Dongosintr N, Wasi C, et al. The regression of recurrent conjunctival papillomas by lymphoblastoid interferon treatment. J Med Assoc Thai. 1990 Jul. 73(7):406-13. [Medline].
Eagle RC. Conjunctiva. Eye Pathology - An Atlas and Basic Text. Philadelphia, Pa: WB Saunders Co; 1999. 47-8, 59, 61-2(chap 4).
Easty DL, Williams C. Viral and rickettsial disease. Garner A, Klintworth GK, eds. Pathobiology of Ocular Disease - A Dynamic Approach. Marcel Dekker Inc; 1994. 247(chap 7).
Harkey ME, Metz HS. Cryotherapy of conjunctival papillomata. Am J Ophthalmol. 1968 Nov. 66(5):872-4. [Medline].
Hsu HC, Lin HF. Eyelid tumors in children: a clinicopathologic study of a 10-year review in southern Taiwan. Ophthalmologica. 2004 Jul-Aug. 218(4):274-7. [Medline].
Jakobiec FA, Harrison W, Aronian D. Inverted mucoepidermoid papillomas of the epibulbar conjunctiva. Ophthalmology. 1987 Mar. 94(3):283-7. [Medline].
Khalil MK, Pierson RB, Mihalovits H, et al. Intraepithelial neoplasia of the bulbar conjunctiva clinically presenting as diffuse papillomatosis. Can J Ophthalmol. 1993 Oct. 28(6):287-90. [Medline].
Kremer I, Sandbank J, Weinberger D, et al. Pigmented epithelial tumours of the conjunctiva. Br J Ophthalmol. 1992 May. 76(5):294-6. [Medline].
Lass JH, Grove AS, Papale JJ, et al. Detection of human papillomavirus DNA sequences in conjunctival papilloma. Am J Ophthalmol. 1983 Nov. 96(5):670-4. [Medline].
Lass JH, Jenson AB, Papale JJ, Albert DM. Papillomavirus in human conjunctival papillomas. Am J Ophthalmol. 1983 Mar. 95(3):364-8. [Medline].
Mantyjarvi M, Syrjanen S, Kaipiainen S, et al. Detection of human papillomavirus type 11 DNA in a conjunctival squamous cell papilloma by in situ hybridization with biotinylated probes. Acta Ophthalmol (Copenh). 1989 Aug. 67(4):425-9. [Medline].
Margo CE, Mack WP. Therapeutic decisions involving disparate clinical outcomes: patient preference survey for treatment of central retinal artery occlusion. Ophthalmology. 1996 Apr. 103(4):691-6. [Medline].
McDonnell JM, Lass JH. Human papillomavirus diseases. Pepose JS, et al, eds. Ocular Infection and Immunity. New York: Mosby; 1996. 857-68(chap 67).
McDonnell JM, McDonnell PJ, Mounts P, et al. Demonstration of papillomavirus capsid antigen in human conjunctival neoplasia. Arch Ophthalmol. 1986 Dec. 104(12):1801-5. [Medline].
McDonnell PJ, McDonnell JM, Kessis T, et al. Detection of human papillomavirus type 6/11 DNA in conjunctival papillomas by in situ hybridization with radioactive probes. Hum Pathol. 1987 Nov. 18(11):1115-9. [Medline].
McLean IW, et al. Tumors of the conjunctiva (Chapter 3). In: Tumors of the Eye and Ocular Adnexa. Atlas of Tumor Pathology. Washington, DC: Armed Forces Institute of Pathology. 1994:49-52.
Mincione GP, Taddei GL, Wolovsky M, et al. Detection of human papillomavirus (HPV) DNA type 6/11 in a conjunctival papilloma by in situ hybridization with biotinylated probes. Pathologica. 1992 Jul-Aug. 84(1092):483-8. [Medline].
Miyagawa M, Hayasaka S, Nagaoka S, Mihara M. Sebaceous gland carcinoma of the eyelid presenting as a conjunctival papilloma. Ophthalmologica. 1994. 208(1):46-8. [Medline].
Morsman CD. Spontaneous regression of a conjunctival intraepithelial neoplastic tumor. Arch Ophthalmol. 1989 Oct. 107(10):1490-1. [Medline].
Omohundro JM, Elliott JH. Cryotherapy of conjunctival papilloma. Arch Ophthalmol. 1970 Nov. 84(5):609-10. [Medline].
Pfister H, Fuchs PG, Volcker HE. Human papillomavirus DNA in conjunctival papilloma. Graefes Arch Clin Exp Ophthalmol. 1985. 223(3):164-7. [Medline].
Rumelt S, Pe'er J, Rubin PA. The clinicopathological spectrum of benign peripunctal tumours. Graefes Arch Clin Exp Ophthalmol. 2005 Feb. 243(2):113-9. [Medline].
Saegusa M, Takano Y, Hashimura M, et al. HPV type 16 in conjunctival and junctional papilloma, dysplasia, and squamous cell carcinoma. J Clin Pathol. 1995 Dec. 48(12):1106-10. [Medline].
Schechter BA, Rand WJ, Velazquez GE, et al. Treatment of conjunctival papillomata with topical interferon Alfa-2b. Am J Ophthalmol. 2002 Aug. 134(2):268-70. [Medline].
Slade CS, Katz NN, Whitmore PV, Bardenstein DS. Conjunctival and canalicular papillomas and ichthyosis vulgaris. Ann Ophthalmol. 1988 Jul. 20(7):251-5. [Medline].
Spencer WH. Neoplasms and related conditions (Chapter 2). In: Ophthalmic Pathology - An Atlas and Textbook. Vol. 1. Philadelphia, Pa: WB Saunders Co. 1996:106-11.
Wells GB, Lasner TM, Yousem DM, Zager EL. Lhermitte-Duclos disease and Cowden's syndrome in an adolescent patient. Case report. J Neurosurg. 1994 Jul. 81(1):133-6. [Medline].
Wilson FM, Ostler HB. Conjunctival papillomas in siblings. Am J Ophthalmol. 1974 Jan. 77(1):103-7. [Medline].
Yanoff M, Fine BS. Conjunctiva - pseudocancerous lesions. Ocular Pathology. 4th ed. New York: Mosby-Wolfe; 1996. 220-1(chap 7).