Genomic alterations in human papillomavirus-positive and -negative conjunctival squamous cell carcinomas

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PURPOSE. The genomic alterations contributing to the pathogenesis of conjunctival squamous cell carcinomas (SCCs) and their precursor lesions are poorly understood and hamper our ability to develop molecular therapies to reduce the recurrence rates and treatment-related morbidities of this disease. We aimed to characterize the somatic DNA alterations in human papillomavirus (HPV)-positive and HPV-negative conjunctival SCC. METHODS. Patients diagnosed with conjunctival SCC in situ or SCC treated in ocular oncology referral centers in Denmark were included. HPV detection (HPV DNA PCR, p16 immunohistochemistry, and mRNA in situ hybridization) and targeted capture-based next-generation sequencing of 523 genes frequently involved in cancer were performed to describe the mutational profile based on HPV status. RESULTS. Tumor tissue was available in 33 cases (n = 8 conjunctival SCCs in situ, n = 25 conjunctival SCCs), constituting 25 male and 8 female patients. Nine cases were HPV positive. The HPV-positive SCCs in situ and SCCs were characterized by transcriptionally active high-risk HPV (types 16 and 39) within the tumor cells, frequent mutations in PIK3CA (n = 5/9), and wild-type TP53, CDKN2A, and RB1, while the HPV-negative counterparts harbored frequent mutations in TP53 (n = 21/24), CDKN2A (n = 7/24), and RB1 (n = 6/24). CONCLUSIONS. Our findings have delineated two potentially distinct distributions of somatic mutations in conjunctival SCC based on HPV status-pointing to different biological mechanisms of carcinogenesis. The present findings support a causal role of HPV in a subset of conjunctival SCC.

TidsskriftInvestigative Ophthalmology and Visual Science
Udgave nummer14
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
Supported by the Svend Helge Arvid Schrøder and Ketty Lydia Larsen Schrøder Foundation, Denmark; the Synoptik Foundation, Denmark; “Fight for Sight, Denmark”; Faculty of Health and Medical Science, University of Copenhagen, Denmark; Copen- hagen University Hospital, Rigshospitalet; and the Danish Eye Research Foundation. The funding sources had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Publisher Copyright:
© 2021 Association for Research in Vision and Ophthalmology Inc.. All rights reserved.

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