Lee and Hirst first described Ocular Surface Squamous Neoplasia (OSSN) 1. The incidence is 0.13-1.9% per lakh. 1 It is an umbrella term, which includes benign to malignant lesions of the conjunctiva. The risk factors are male gender, old age, UV exposure, Immunosuppression, Smoking, Vitamin A deficiency, HIV infections, Hepatitis B, and HPV(Human Papilloma Virus) 16 and 18 (high-risk types). 2 The prevalence of Conjunctival papilloma associated with HPV is 44-92%, and of Squamous cell carcinoma (SCC) is 33%. 3 Verruca Vulgaris (VV) or Common warts are caused by epidermal infection caused by HPV 6 and 11 (Low-risk types). 4 The incidence of common warts among the general population is 1-13%4. Reports of co-existent conjunctival papillomas and verruca Vulgaris implies that the HPV infection can co-occur at multiple sites. 4, 5 The other skin conditions associated with OSSN include Papillon-Lefevre syndrome, 6 Xeroderma pigmentosa, 7 Non-Hodgkin's lymphoma, 8 congenital ichthyosis, 9 and Epidermodysplasia verriciformis. 10 Verruca Vulgaris and associated mucosal type of SCC have not been previously reported in the literature. We report a case of conjunctival SCC in association with verruca Vulgaris.
A 30-year-old male, farmer by occupation, presented to us with redness in the left eye for the past 3months. The best Corrected Visual Acuity in both eyes was 20/20. Recent medical history included dermatology consultation for an unknown skin disease. On general examination, diffuse, multiple, elevated cauliflower-like lesions were seen all over the arms, legs, and face (Figure 1). Ocular inspection of the right eye was within normal limits. The left eye revealed diffuse, elevated, pink, fleshy gelatinous growth around the limbus, invading 2mm of cornea extending nasally from 5 to 1’oclock hours and sentinel vessels (Figure 2a). The skin biopsy revealed acanthosis with downward invaginations and papillomatosis with marked surface keratinization- church-spire keratosis. The subepithelial tissue was hyperemic and is infiltrated with few mononuclear inflammatory cells, and koliocytes were present. The complete blood counts were normal. ELISA for HIV, VDRL/RPR, HBsAg was non-reactive. Hence the clinical diagnosis of OSSN was made. Since the OSSN involves more than six clock hours, an incisional biopsy was done. The biopsy report showed squamous cell carcinoma. To avoid surgical complications such as LSCD, conjunctival scarring, and symblepharon, Mitomycin-C (MMC) 0.04% was started, one drop four times daily for a week and one week off cycle. After three cycles of chemotherapy, the lesion completely regressed (Figure2b and c). The sequence was continued for one more week with MMC 0.02% to prevent the recurrence. The patient is on regular follow-up for the past one year, and no recurrence was noted (Figure 2d).
Verruca Vulgaris is a skin condition caused by HPV 6 & 11.4, 11 They rarely occur on the eyelids, but if seen, typically appear near the lid margin. The risk factors are the usage of public showers, meat cutters, eczema, and a weak immune system.12 The lesions appear diffuse, hyperkeratotic, exophytic, and dome-shaped papules or nodules and typically multiple, or sessile, with discrete borders.12 Diagnosis is clinically confirmed by hemorrhages caused by cutting the wart horizontally with a scalpel or piercing it.4 They spread by direct contact or autoinoculation.4
It is a benign condition but frequently has been reported with squamous cell carcinoma of the skin. Kopelson et al. 13 reported SCC at the verruca Vulgaris, in the finger (10 out of 32 patients). Zaesim et al. reported SCC arising within the verruca Vulgaris on the nipple in a 49-year-old Caucasian woman, and the association was confirmed by positive Immunohistochemical testing for HPVL1 capsid protein.14 The association of conjunctival papillomas and Verrucae Vulgaris, which shares the common etiological factor HPV, can occur together, but conjunctival SCC and Verruca Vulgaris have not been reported previously in the literature. The presence of Koliocytosis is the pathognomic feature of HPV infection, though not confirmatory for diagnosis. Carreira H et al. in his systematic review and meta-analysis to quantify the association between HIV and HPV infection and OSSN reported that HIV was associated with the risk of OSSN and in HPV; only cutaneous types seem to be a risk factor and not the mucosal types.15
Our case was peculiar in which the patient presented to us with extensive OSSN involving the limbus and cornea. The incisional biopsy revealed the SCC and had an excellent prognosis with chemotherapy. The recovery time was six weeks. The SCC can occur with other skin conditions such as EDV,10 Xeroderma pigmentosa,7 and Congenital Ichthyosis,9 but uncommon with verruca Vulgaris. The common etiological association would be the HPV. The other skin condition associated with HPV infection is Epidermodysplasia verruciformis (EDV).10 It is also known as tree man syndrome, is a rare, autosomal recessive disorder with a high risk of skin cancer in 30-70% individuals. It is characterized by abnormal susceptibility to HPV infections. EDV is caused by multiple types of HPV, 3,8,10, and 14 in 86% of cases, suggesting the strong association of HPV with SCC of skin. It is characterized by scaly macules and papules resembling tree bark, particularly on the hands and feet.10
To conclude, the association of Verruca Vulgaris and conjunctival SCC has not been reported in the literature. HPV is the common etiological factor between Verruca Vulgaris and OSSN; the presence of koliocytes in the biopsy report suggested the same.