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Pavan Mann, Scott Diamond, Rangarirai Masanganise, Lovemore Gwanzura, Yu-Tsueng Liu, Robert T Schooley, Jonathan H Lin; HPV16/18 and p16 gene expression in ocular surface squamous neoplasia: a retrospective cross-sectional analysis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5594. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Human papillomavirus (HPV) infection is an important risk factor for squamous neoplasms of the cervix, head, and neck. HPV’s role in ocular surface squamous neoplasia (OSSN), including conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC), is unclear. HIV-seropositive (HSP) populations have increased susceptibility to HPV infections, HPV-linked cancers, and an increased prevalence of OSSN. To determine if OSSN was related to HPV infection in HSP patients, we performed a retrospective, cross-sectional analysis of 49 OSSN patient biopsies for expression of HPV 16/18 viral genes and p16, a biomarker of HPV-infected keratinocytes.
Biopsies obtained from 49 Zimbabwean patients (28 female, 21 male, ages 18-67 years) were formalin fixed, paraffin-embedded, cut, and stained with hematoxylin and eosin (H&E) to diagnose OSSN and classify as CIN or SCC. In parallel, nucleic acid extracted from biopsies was assayed by quantitative RT-PCR for p16 and HPV 16/18 E6/E7 transcript expression. HeLa, CaSki, and SiHa cells constitutively expressing HPV oncogenes served as positive controls. HeLa cells were used as positive control for p16 status, with positivity defined as p16 deltaCT <10.3727 cycles.
CIN was diagnosed in 19 OSSN biopsies (39%), and SCC was diagnosed in 30 (61%). All 49 cases were negative for both HPV 16 and 18 oncogenes. p16 expression was detected in 13 OSSN cases (26%); 7 CIN cases (37%), and 6 SCC cases (20%). 43 patients were HSP (88%); 14 CIN cases (74%), and 29 SCC cases (97%). 1 patient was p16+ and HIV-seronegative (2%), while 11 patients were both p16+ and HSP (22%); 5 CIN cases (26%), and 6 SCC cases (20%).
Our study shows no relationship between HPV 16/18 infection and OSSN, as determined by qPCR measurements of HPV oncogene expression, suggesting that HPV infection does not explain the increased prevalence of OSSN found in this patient population. Interestingly, increased p16 gene expression was found in a minority of OSSN cases in the absence of HPV oncogene expression. This p16 positivity was more prevalent in HSP cases than HIV-seronegative cases (22% vs. 2%), and SCC is more prevalent in HSP cases (97% HSP SCC cases, vs. 74% HSP CIN cases). Our data suggest that increased p16 expression in OSSN does not correspond with high-risk HPV infection, but may be associated with more aggressive OSSNs in HSP patients.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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