Young patients with head and neck squamous cell carcinoma (HNSCC) appear to have unique clinical profiles based on history of alcohol and tobacco abuse.

Human papillomavirus (HPV), a known etiology of a subset of head and neck squamous cell carcinomas (HNCs), causes numerous alterations in normal cellular functions. This article reviews the biology, detection and treatment of HPV-positive HNC. The role of HPV oncoproteins in tumor development, the natural history of HPV infection, and risk factors for and prevention of transmission of oral HPV are considered. Commonly used methods for detecting HPV infection including limitations of these methods are discussed to aid the practicing clinician in utilizing these tests in their clinical practice. Clinical characteristics of HPV-positive HNC including potential explanations for the improved outcomes seen in patients with HPV-positive HNC are assessed. Ongoing clinical trials specific for patients with HPV-positive HNC are described and areas in need of additional research are summarized. Until the results of ongoing trials are known, treatment of HPV-positive HNC should not differ in clinical practice from treatment of similar non-HPV related cancers.

Background. The aim of this study was to examine biomolecular profiles in a cohort of young adults with squamous cell cancers (SCCs) of the oral tongue.Methods. We identified all patients aged 18 to 39 years diagnosed with SCC of the oral tongue at our institution. Immunohistochemical (IHC) staining was performed for p16 INK4a , epidermal growth factor receptor (EGFR), phosphorylated-EGFR (pEGFR), p53, and ERCC1. Human papillomavirus (HPV) testing was performed using in situ hybridization (ISH) and polymerase chain reaction (PCR). Biomarker expression and HPV status were correlated with outcomes.Results. We identified 25 patients with sufficient tumor samples. Median age at diagnosis was 30 years (range, 20-39 years). p16INK4a overexpression was observed in 11 of 25 patients, whereas HPV-16 positivity was observed in none of the tumor samples by ISH and 2 of the tumor samples by PCR. p16INK4a positivity was correlated with improved relapse-free survival (hazard ratio [HR] ¼ 0.23, p ¼ .01) and overall survival (HR ¼ 0.28, p ¼ .05). Neither EGFR, pEGFR, p53, nor excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) expression correlated with outcome on univariate analysis.Conclusions. p16 INK4a overexpression was common and was a marker of favorable prognosis. p16INK4a overexpression was not a reliable predictor of HPV positivity in our cohort.

In a theoretical analysis of a single pair of high-class gears three internal sources of vibration are considered: (1) Periodic variations in the velocity ratio due either to running the gears above or below the designed load, or to small manufacturing errors. (2) Period variation in the tooth stiffness. (3) Non-linearity in tooth stiffness. The amplitudes of vibrations caused by (1) depend on damping, while those caused by (2) or (3) will only occur if the damping is below a limit estimated at 0.07 of critical damping. Damping currently reported for tests on steel gears is about 0.1 of critical, but might well be less. Dynamic tooth forces and amplitudes of vibration were found from photo-elastic stress patterns of model gears with both small and large errors. The more accurate gears showed only vibration caused by (1), variation in the velocity ratio, because the damping was too great for the other modes. Information on damping is insufficient for satisfactory prediction of dynamic increments. If the damping in any gears fell to 0.07 of critical the increment, instead of having a small value, might equal the applied load, irrespective of any errors, and this might prove disastrous.

Purpose We evaluated X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) protein in head and neck squamous cell carcinoma (HNSCC) patients in association with outcome. Experimental Design XRCC1 protein expression was assessed by immunohistochemical (IHC) staining of pretreatment tissue samples in 138 consecutive HNSCC patients treated with surgery (n = 31), radiation (15), surgery and radiation (23), surgery and adjuvant chemoradiation (17), primary chemoradiation (51), and palliative measures (1). Results Patients with high XRCC1 expression by IHC (n = 77) compared with patients with low XRCC1 expression (n = 60) had poorer median overall survival (OS; 41.0 months vs. OS not reached, P = 0.009) and poorer progression-free survival (28.0 months vs. 73.0 months, P = 0.031). This association was primarily due to patients who received chemoradiation (median OS of high- and low-XRCC1 expression patients, 35.5 months and not reached respectively, HR 3.48; 95% CI: 1.44–8.38; P = 0.006). In patients treated with nonchemoradiation modalities, there was no survival difference by XRCC1 expression. In multivariable analysis, high XRCC1 expression and p16INK4a-positive status were independently associated with survival in the overall study population (HR = 2.62; 95% CI: 1.52–4.52; P < 0.001 and HR = 0.21; 95% CI: 0.06–0.71; P = 0.012, respectively) and among chemoradiation patients (HR = 6.02; 95% CI: 2.36–15.37; P < 0.001 and HR = 0.26; 95% CI: 0.08–0.92, respectively; P = 0.037). Conclusions In HNSCC, high XRCC1 protein expression is associated with poorer survival, particularly in patients receiving chemoradiation. Future validation of these findings may enable identification of HNSCC expressing patients who benefit from chemoradiation treatment.

Hip dysplasia, an abnormal laxity of the hip joint, is seen in humans as well as dogs and is one of the most common skeletal disorders in dogs. Canine hip dysplasia is considered multifactorial and polygenic, and a variety of chromosomal regions have been associated with the disorder. We performed a genome-wide association study in Dutch Labrador Retrievers, comparing data of nearly 18,000 single nucleotide polymorphisms (SNPs) in 48 cases and 30 controls using two different statistical methods. An individual SNP analysis based on comparison of allele frequencies with a χ2 statistic was used, as well as a simultaneous SNP analysis based on Bayesian variable selection. Significant association with canine hip dysplasia was observed on chromosome 8, as well as suggestive association on chromosomes 1, 5, 15, 20, 25 and 32. Next-generation DNA sequencing of the exons of genes of seven regions identified multiple associated alleles on chromosome 1, 5, 8, 20, 25 and 32 (p<0.001). Candidate genes located in the associated regions on chromosomes 1, 8 and 25 included LAMA2, LRR1 and COL6A3, respectively. The associated region on CFA20 contained candidate genes GDF15, COMP and CILP2. In conclusion, our study identified candidate genes that might affect susceptibility to canine hip dysplasia. These genes are involved in hypertrophic differentiation of chondrocytes and extracellular matrix integrity of basement membrane and cartilage. The functions of the genes are in agreement with the notion that disruptions in endochondral bone formation in combination with soft tissue defects are involved in the etiology of hip dysplasia.

In an earlier paper by one of the authors (9) a theoretical analysis suggested that, at certain speeds, large vibrations can occur in a pair of spur gears, without any manufacturing errors and without any external excitation, provided the damping is less than about 0·07 of critical. In this paper a summary is given of an extension to this theoretical analysis, but the main part is concerned with experimental observations on a back-to-back gear test rig. From these observations the maximum dynamic loads on the teeth have been deduced. It has been found that for all applied loads between zero and 1 1/4 times design load, the maximum dynamic load never exceeds twice the design load (the design load is the load which gives a constant transmission error at low speed). It should be noted that if the design load (for which the profile modification is specified) is appreciably greater than the applied load, the dynamic increment may be very large. Excessive profile modification should therefore be avoided. As the damping in the rig is only about 0·02 of critical, these figures are likely to be an upper limit for isolated, precision spur gears.

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