AimsHuman papillomavirus (HPV) is considered a causative agent for the development of a broad range of human carcinomas. The role of HPV in the development of conjunctival intraepithelial neoplasia (CIN) and carcinoma (cSCC) remains unclear. The purpose of the present study was to investigate the HPV prevalence in a nationwide cohort and to describe clinical and histopathological features in relation to HPV status.MethodsAll cases of CIN and cSCC in Denmark from 1980 to 2016 were included. We combined p16 immunohistochemistry (IHC), RNA in situ hybridisation (RNA ISH) and HPV DNA PCR to detect HPV. The results were correlated to clinical and histopathological parameters.ResultsOne hundred twelve primary tumours and 33 recurrent tumours were included for HPV analysis. Twenty-four (21%) of the primary tumours were HPV positive by PCR. Eighteen of out 19 HPV-positive tumours were positive by RNA ISH. HPV16 was the most prevalent genotype (n=18, 75%). The patients with HPV-positive tumours were significantly younger (mean difference 11.5 years, 95% CI 5.2 to 17.9, p=0.0005) and had a higher recurrence compared with patients with HPV-negative tumours (HR 2.30, 95% CI 1.02 to 5.21, p=0.046). The HPV-positive tumours were associated with a positive p16 IHC and a non-keratinising morphology.ConclusionWe describe distinct clinical and histopathological features associated with HPV status in cSCC. The finding of transcriptionally active HPV in this material lends support to a causal role of HPV in a subset of cSCC.
ABSTRACT.Purpose: To compare the basic proteomic composition of aqueous humour (AH) from patients with corneal rejection (patients) with AH from patients with cataract (controls). Methods: Aqueous humour was analysed for total protein concentration using Bradford's method and for protein composition using two-dimensional (2D) gel electrophoresis. Image analysis was used to detect protein spots in 2D gels that were increased by more than factor 2 in patients as compared with controls. Increased spots were identified by immunoblotting and mass spectrometry. Results: Aqueous humour from patients contained significantly higher total protein concentration than did AH from controls. A total of 31 spots were significantly increased in 2D gels from patients. The spots were derived from albumin, a1-antitrypsin, apolipoprotein J, cytokeratin type II, serin proteinase inhibitor and transthyretin. After correction of spot volumes by total protein concentrations, 10 spots derived from albumin, cytokeratin type II and a1-antitrypsin remained significantly increased. Conclusion: The proteomic composition of AH differed significantly between patients and controls. The identified proteins suggest that the changes in AH are due to at least three different mechanisms: breakdown of the aqueous-blood barrier, enzymatic degradation, and liberation of locally synthesized proteins.
Key Points Question Are heritability and treatment associated with the incidence of second primary cancer in Danish retinoblastoma survivors? Findings In this national cohort study of 323 patients in Denmark diagnosed with retinoblastoma, the incidence and mortality of second primary cancer were significantly higher in patients with heritable retinoblastoma vs patients with nonheritable retinoblastoma. The data did not show an increased risk in patients with heritable disease who were treated with external radiotherapy. Meaning The findings of this study suggest that patients with a genetic predisposition to retinoblastoma may be at greater greatest risk for developing second primary cancer later in life.
Purpose We aimed to study the prevalence of human papillomavirus (HPV) in conjunctival intraepithelial neoplasia and carcinoma. Furthermore, we aimed to explore whether geographical differences or different detection modalities are associated with the conflicting information regarding HPV and the development of the disease. Methods We searched the MEDLINE, EMBASE and Scopus databases for studies reporting on HPV and conjunctival intraepithelial neoplasia or carcinoma. The pooled prevalence proportions, odds ratio (OR) and corresponding 95% confidence intervals were calculated assuming a random‐effects model. Subgroup analyses and meta‐regression explored possible sources of heterogeneity. Results A total of 39 studies were included in the systematic review. The pooled prevalence of HPV in conjunctival intraepithelial neoplasia and carcinoma was 26%, with HPV16, 18, and 33 being the most frequently reported genotypes. Human papillomavirus (HPV) infection was associated with an increased risk of conjunctival intraepithelial neoplasia and carcinoma (OR 8.4, 95% confidence interval (CI) 3.7–19.1); lower in studies from African countries (OR 1.7, 95% CI 0.9–3.5) than other countries (OR 16.1, 95% CI 5.8–44.3), p = 0.013. Conclusion Human papillomavirus infection increases the odds of conjunctival intraepithelial neoplasia and carcinoma by 8.4 compared to healthy conjunctival mucosa or other ocular surface diseases. There seem to be geographical differences regarding HPV in conjunctival intraepithelial neoplasia and carcinoma. HPV16 was the most prevalent genotype, followed by HPV18 and HPV33, meaning that most of the HPV‐related conjunctival intraepithelial neoplasia and carcinoma may be prevented by the HPV vaccines that are currently available.
The optics of the pseudophakic eye can be accurately described using exact ray tracing and modern biometric techniques.
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