Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient treatment decision. We characterize head and neck squamous cell carcinomas (HNSCC) with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited patients by gene expression profiling and targeted sequencing of 50 genes. We show that tumors with transcriptionally inactive HPV16 (DNA1 RNA-) are similar to HPV-negative (DNA-) tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and

Acta Ophthalmol. 2010: 88: 717–722 Abstract. The present article describes a standard instrument for the continuous online determination of retinal vessel diameters, the commercially available retinal vessel analyzer. This report is intended to provide informed guidelines for measuring ocular blood flow with this system. The report describes the principles underlying the method and the instruments currently available, and discusses clinical protocol and the specific parameters measured by the system. Unresolved questions and the possible limitations of the technique are also discussed.

To determine the sensitivity and specificity of HPV16 serology as diagnostic marker for HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), 214 HNSCC patients from Germany and Italy with fresh-frozen tumor tissues and sera collected before treatment were included in this study. Hundred and twenty cancer cases were from the oropharynx and 94 were from head and neck cancer regions outside the oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx). Serum antibodies to early (E1, E2, E6 and E7) and late (L1) HPV16 proteins were analyzed by multiplex serology and were compared to tumor HPV RNA status as the gold standard. A tumor was defined as HPV-driven in the presence of HPV16 DNA and HPV16 transformation-specific RNA transcript patterns (E6*I, E1 E4 and E1C). Of 120 OPSCC, 66 (55%) were HPV16-driven. HPV16 E6 seropositivity was the best predictor of HPV16-driven OPSCC (diagnostic accuracy 97% [95%CI 92-99%], Cohen's kappa 0.93 [95%CI 0.8-1.0]). Of the 66 HPV-driven OPSCC, 63 were HPV16 E6 seropositive, compared to only one (1.8%) among the 54 non-HPV-driven OPSCC, resulting in a sensitivity of 96% (95%CI 88-98) and a specificity of 98% (95%CI 90-100). Of 94 HNSCC outside the oropharynx, six (6%) were HPV16-driven. In these patients, HPV16 E6 seropositivity had lower sensitivity (50%, 95%CI 19-81), but was highly specific (100%, 95%CI 96-100). In conclusion, HPV16 E6 seropositivity appears to be a highly reliable diagnostic marker for HPV16-driven OPSCC with very high sensitivity and specificity, but might be less sensitive for HPV16-driven HNSCC outside the oropharynx.

We cross-sectionally examined the relationship between age, optic disc area, refraction, and gender and optic disc topography and retinal nerve fiber layer (RNFL) measurements, using optical imaging techniques. One eye from each of 155 Caucasian subjects (age range 23.0-80.8 y) without ocular pathology was included. Measurements were obtained by using the Heidelberg Retina Tomography (HRT), the GDx Nerve Fiber Analyzer, and the Optical Coherence Tomograph (OCT). The effects of age were small (R2 < 17%) and were limited to specific HRT, GDx, and OCT parameters. Disc area was significantly associated with most HRT parameters and isolated GDx and OCT parameters. Refraction and gender were not significantly associated with any optic disc or RNFL parameters. Although effects of age on the optic disc and RNFL are small, they should be considered in monitoring ocular disease. Optic disc area should be considered when cross-sectionally evaluating disc topography and, to a lesser extent, RNFL thickness.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) can characterize perfusion and vascularization of tissues. DCE MRI parameters can differentiate between malignant and benign lesions and predict tumor grading. The purpose of this study was to correlate DCE MRI findings and various histopathological parameters in head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Sixteen patients with histologically proven HNSCC (11 cases primary tumors and in 5 patients with local tumor recurrence) were included in the study. DCE imaging was performed in all cases and the following parameters were estimated: Ktrans, Ve, Kep, and iAUC. The tumor proliferation index was estimated on Ki 67 antigen stained specimens. Microvessel density parameters (stained vessel area, total vessel area, number of vessels, and mean vessel diameter) were estimated on CD31 antigen stained specimens. Spearman's non-parametric rank sum correlation coefficients were calculated between DCE and different histopathological parameters. RESULTS: The mean values of DCE perfusion parameters were as follows: Ktrans 0.189 ± 0.056 min−1, Kep 0.390 ± 0.160 min−1, Ve 0.548 ± 0.119%, and iAUC 22.40 ± 12.57. Significant correlations were observed between Kep and stained vessel areas (r = 0.51, P = .041) and total vessel areas (r = 0.5118, P = .043); between Ve and mean vessel diameter (r = −0.59, P = .017). Cell count had a tendency to correlate with Ve (r = −0.48, P = .058). In an analysis of the primary HNSCC only, a significant inverse correlation between Ktrans and KI 67 was identified (r = −0.62, P = .041). Our analysis showed significant correlations between DCE parameters and histopathological findings in HNSCC.

PET/MRI of patients with head and neck cancer yielded good diagnostic capability, similar to PET/CT. Further studies on larger cohorts to prove these first results seem justified.

Measurements with the DCT showed good concordance with intracameral IOP. CCT exerted a statistically significant but clinically irrelevant effect on measurements with the DCT.

ABSTRACT.Purpose: To determine whether corneal hysteresis (CH) and corneal resistance factor (CRF) are altered in diabetes and whether these parameters are related to HbA1c. Methods: One randomly chosen eye of 35 healthy subjects and 31 patients with diabetes was examined. Patients with diabetes were divided into group 1 with HbA1c <7% (n = 14) and group 2 with HbA1c ‡7% (n = 17). CH and CRF were measured using ocular response analyzer (ORA); central corneal thickness (CCT) using ultrasound pachymetry; increased intraocular pressure (IOP) using Goldmann tonometer (IOP GAT ), Pascal dynamic contour tonometer (IOP pasc ), and ORA (IOP cc ). As CH and CRF are dependent on IOP and CCT, they were adjusted for IOP and CCT resulting in CH corr and CRF corr. Results: Mean HbA1c was 5.44 ± 0.46% in healthy subjects, 6.00 ± 0.78% in diabetic group 1, 8.58 ± 2.44% in group 2. CH corr (p = 0.071) and CRF corr (p = 0.067) were not statistically significantly different between healthy subjects and diabetic group 1, but significantly lower in healthy subjects compared to diabetic group 2 [CH corr (p = 0.031), CRF corr (p = 0.029)]. IOP pasc (p = 0.012), IOP GAT (p = 0.032) and HbA1c (p = 0.0001) were statistically significantly different between healthy subjects and all patients with diabetes (groups 1 + 2), but not age, sex and CCT. Over all patients with diabetes, CH corr (p = 0.012, R 2 = 0.197) and CRF corr (p = 0.008, R 2 = 0.217) were correlated to HbA1c but not in healthy subjects [CH corr (p = 0.931, R 2 = 0.0001), CRF corr (p = 0.837, R 2 = 0.001)]. Conclusion: In poorly controlled diabetics, CH corr and CRF corr are significantly higher compared with those of the healthy subjects and patients with well-controlled diabetes. In diabetes, CH corr and CRF corr are correlated to HbA1c, suggesting that the biomechanical properties of the cornea are altered depending on the glucose control.