Abstract
Backgroundp16 expression is a well established biomarker of cervical dysplasia and carcinoma arising from high risk human papilloma virus infection. Increased p16 expression is also seen in squamous neoplasms arising at other sites, including head, neck, and oropharyngeal tract. Squamous lesions are also frequently encountered at ocular surface and peri-orbital skin sites, but the prevalence of increased p16 expression in these lesions has been poorly studied.MethodsWe retrospectively surveyed 13 ocular surface and 16 orbital squamous lesions biopsied at UC San Diego Healthcare System and VA San Diego Healthcare System for p16 expression by immunohistochemistry. These cases included ocular surface lesions with diagnoses of conjunctival intraepithelial neoplasm (CIN) and squamous cell carcinoma in situ. Peri-orbital eyelid biopsies included lesions with diagnoses of SCCis and invasive squamous cell carcinoma. We performed multivariate logistic regression, followed by student’s T-test or Fisher's exact test to determine if there were statistically significant associations between p16 immunoreactivity and patient age, gender, diagnosis, and ethnicity. Statistical significance was defined as p < 0.05.ResultsWe found an unexpectedly large prevalence of strong nuclear and cytoplasmic p16 immunoreactivity in our cases. Almost all of the ocular surface squamous lesions were diffusely positive for p16 expression (12/13). All of the periorbital lesions showed diffuse p16 immunoreactivity (16/16). Altogether, 28/29 lesions tested showed strong and diffuse p16 expression. We found no statistically significant correlation between p16 expression and patient age, gender, ethnicity, or diagnosis. In 6 of the peri-orbital biopsies, we had sufficient tissue to assess high-risk HPV expression by in situ hybridization. Interestingly, all of these cases were negative for HPV, despite strong p16 expression.ConclusionStrong p16 expression was observed in virtually all of the ocular surface and peri-orbital squamous neoplasms in our study. The relationship between p16 expression and HPV infection in ocular surface and peri-orbital sites requires further investigation.
Highlights
HPV is linked to development of cervical, anogenital, head/neck, and lung squamous lesions and carcinomas [1,2,3,4,5]
We examined 29 ocular surface and periorbital squamous lesions excised at our institution that comprised malignant (CIN and squamous cell carcinoma (SCC)) ocular squamous neoplasms
Tissue specimens We examined a total of 29 ocular surface and periorbital eyelid squamous lesion cases retrieved from the VA San Diego and UCSD Medical Center between July 2010May 2014
Summary
HPV is linked to development of cervical, anogenital, head/neck, and lung squamous lesions and carcinomas [1,2,3,4,5]. HPV has been detected in prior studies of ocular and peri-ocular squamous lesions and suggested to contribute to the pathogenesis of squamous lesions in the eye [18,19,20,21]. Very few studies have examined p16 expression in squamous lesions resected from the eye, and there have been conflicting findings from these reports. In a cohort of HIV seropositive patients in Africa, Mwololo and colleagues findings found strong p16 immunoreactivity in 67 % (39 of 58) of SCC conjunctival biopsies [22]. In a study of ocular surface and conjunctival squamous lesions performed in Australia, Woods and colleagues found p16 immunoreactivity in only 6.5 % (3 of 46) ocular surface squamous neoplasia biopsies and 12.5 % (3 of 24) conjunctival SCCs [23]. P16 immunoreactivity completely correlated with HPV detection by PCR in this study [23]
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