A Spectrum of Bilateral Squamous Conjunctival Tumors Associated with Human Papillomavirus Type 16 MARC G. ODRICH, MD, 1 FREDERICK A. JAKOBIEC, MD, 1 WAYNE D. LANCASTER, PhD, 2 KENNETH R. KENYON, MD, 1 LISA D. KELLY, MD, 1 ERNEST W. KORNMEHL, MD,t ROGER F. STEINERT, MD,t ARTHUR S. GROVE, Jr., MD,t JOHN W. SHORE, MD,t LUCIE GREGOIRE, MS,3 DANIEL M. ALBERT, MD l Abstract: Three patients with bilateral tumors presenting as multiple keratinizing and verrucous lesions of the bulbar and tarsal conjunctiva were determined by DNA amplification and hybridization studies to harbor human papillomavirus type 16 (HPV-16)o Results of biopsy in two patients showed infiltrating squamous cell carcinoma in one eye and dysplasia or carcinoma in situ in the fellow eye. In the third patient, focal, inflamed, hypertrophic, papillary lesions with pseudo- glandular invaginations of the surface epithelium were found in the tarsal con- junctivae of both eyes. These are the first documented cases of bilateral con- junctival tumors associated with human papillornavirus. Ophthalmology 1991; 98:628-635 Papillomata of the conjunctiva are relatively uncom- mon, but not rare, and typically develop over a period of months. 1 They are known to occur in all age groups, but predominantly they develop in patients older than 40 years of age. 1 Duke-Elder divides these lesions into groups of Originally received: January 23, 1990. Revision accepted: December 14, 1990, 1 Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston. 2 Departments of Molecular Biology and Genetics and Obstetrics and Gynecology, Center for Molecular Biology, Wayne State University School of Medicine, Detroit. 3 Department of Microbiology and Immunology, University of Ottawa, and Laboratory of Medicine, Ottawa Civic Hospital, Ottawa, Ontario. Reprint requests to Frederick A. Jakobiec, MD, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114. 628 viral origin and neoplastic origin but recognizes that, his- tologically, these two variants are indistinguishable. The ophthalmologic literature is not alone in describing verrucous lesions of mucous membranes as either papil- lomata or, when more invasive, as squamous cell carci- nomas. The cervix, vulva, penis, and oral cavity have each demonstrated the ability to produce such benign and ma- lignant verrucous proliferations.t? In both the recent gy- necologic and dermatologic literature, human papillo- mavirus type 16 (HPV-16) has been linked strongly with neoplasia and carcinoma, while HPV types 6 and 11 have been associated with more benign Iesions.Y Dysplasias of the conjunctiva that display cytoplasmic clearing along with nuclear pyknosis have led ophthalmic pathologists to suggest HPV as an etiology. These histo- logic hallmarks are termed "koilocytosis," as has been demonstrated in warts and in lesions adjacent to frank malignancies of gynecologic, oral, and dermatologic tis- sues associated with HPV. 10-13 It is only recently that