Background
Papilloma is a histopathological term describing tumors with specific morphology. They take on a classic fingerlike or cauliflowerlike appearance. Papillomatous lesions often are lobulated with a central vascular core. Irrelevant of its cytology, a neoplasm of epithelial origin with this form of growth is also called papilloma. Papillomas can be benign or malignant and can be found in numerous anatomic locations (eg, skin, conjunctiva, cervix, breast duct). Specifically, conjunctival papillomas are benign squamous epithelial tumors with a minimal propensity toward malignancy.
Conjunctival papillomas are categorized into infectious (viral), squamous cell, limbal, and inverted (histological description) based on appearance, location, patient's age, propensity to recur after excision, and histopathology. They demonstrate an exophytic growth pattern. Interestingly, inverted papillomas exhibit exophytic and endophytic growth patterns.
Conjunctival papilloma also can be classified based on gross clinical appearance, as either pedunculated or sessile. The pedunculated type is synonymous with infectious conjunctival papilloma and squamous cell papilloma. The limbal conjunctival papilloma often is referred to as noninfectious conjunctival papilloma because it is believed that limbal papillomas arise from UV radiation exposure. Because of its gross appearance, limbal papillomas are typed as sessile. Although rare, inverted conjunctival papillomas sometimes are referred to as mucoepidermoid papillomas because these lesions possess both a mucous component and an epidermoid component.
A strong association exists between human papillomavirus (HPV) types 6 and 11 and the development of conjunctival papillomas. Infectious conjunctival papillomas also are known as squamous cell papillomas. This term arises from its histopathological appearance (ie, the lesion is confined to the epithelial layer, which is acanthotic).
Pathophysiology
Human papillomavirus (HPV) and polyomavirus are members of the Papovavirus family. These viruses are small (55 nm), naked, and icosahedral with circular double-stranded DNA. Papillomaviruses exhibit site and cell-type specificity, as follows:
-
HPV 6 and 11 – Benign skin warts or condylomas of the female genital tract and conjunctival papilloma
-
HPV 16 and 18 – Cervical carcinoma
HPV 6a and 45, 2 new subtypes, have been reported to be associated with conjunctival papilloma. [1, 2]
Transmission is via direct human contact. The proliferation of dermal connective tissue is followed by acanthosis and hyperkeratosis. HPV is tumorigenic, and it commonly produces benign tumors with low potential for malignancy. In general, prolonged proliferation may lead to cellular atypia and dysplasia. HPV type 11 was the most common and frequently found in conjunctival papilloma as analyzed by polymerase chain reaction (PCR). [3]
Epidemiology
Frequency
United States
The literature reviewed yielded no published study outlining the prevalence of conjunctival papillomas in a cross-section of a population. Interestingly, studies are numerous for extraocular sites. Prevalence of conjunctival papillomas ranged from 4-12%. A strong association exists between HPV and squamous cell papilloma. Moreover, the HPV genome is identifiable in most conjunctival papillomas and in 85% of conjunctival dysplasias and carcinomas.
Although no cross-section epidemiological studies are available, evidence suggests that people without overt clinical presentation may harbor the virus, and HPV DNA can be identified in asymptomatic conjunctiva. HPV types 6 and 11 are the most frequently found in conjunctival papilloma. HPV type 33 is another source in the pathogenesis of conjunctival papilloma. HPV types 16 and 18 commonly are associated with not only high-grade cervical intraepithelial neoplasia and invasive carcinoma but also squamous cell dysplasia and carcinoma of the conjunctiva. The recurrence rate for infectious papillomas is high. Limbal papillomas have a recurrence rate of 40%.
Mortality/Morbidity
Conjunctival papillomas (squamous cell, limbal, or inverted) are not life-threatening. Conjunctival papillomas may be large enough to be displeasing or cosmetically disfiguring. HPV types 6 and 11 may be transferred to the child during parturition from an infected birth canal resulting in ocular symptoms.
Egbert et al reported a case of conjunctival papilloma in an infant born to a mother with HPV infection of the vulva during pregnancy. [4] Those infected at birth may later develop respiratory papillomatosis, which may be life-threatening. Direct contact with contaminated hands or objects may result in ocular manifestations.
Squamous cell papilloma, which has an infectious viral etiology, has the propensity to recur after medical and surgical treatment. New and multiple lesions may arise after excision. Recurrent conjunctival papillomas may extend into the nasolacrimal duct causing obstruction. Lauer et al and Migliori and Putterman reported a case of nasolacrimal duct obstruction after extension of the papillomas into the lacrimal sac. [5, 6] Most papillomas are benign. Rarely, they can undergo malignant transformation, signs of which include inflammation, keratinization, and symblepharon formation.
Age
Squamous cell papillomas (ie, infective papilloma, viral conjunctival papilloma) are seen commonly in children and young adults, usually younger than 20 years. Because HPV is associated strongly with this form of papilloma, siblings, including twins, also may be affected. Limbal papillomas are seen commonly in older adults. A slight association exists between UV radiation and limbal conjunctival papilloma.
Prognosis
The prognosis for patients with this condition is generally good.
Recurrences of viral papillomas are not uncommon.
Recurrences of completely excised squamous cell papillomas are uncommon.
Patients should receive routine follow-up care for recurrences.
Patient Education
Inform patients that the lesion may recur after excision and that multiple recurrences are not uncommon.
Recurrence of lesions may require more aggressive treatment.
Theoretically, decreasing sun exposure may prevent squamous cell lesions.
