Studies on human papillomaviruses in head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The traditional risk factors for HNSCC are smoking and alcohol. However, recently IARC has also recognized human papillomaviruses (HPV) as an etiological factor for oropharyngeal cancer, a subset of head and neck cancers. Among oropharyngeal cancer, tonsillar and tongue base cancer dominate, both often associated with HPV. The aim of the present study was to examine the involvement of human papillomavirus (HPV) in two subtypes of HNSCC, tonsillar and hypopharyngeal cancer. For tonsillar cancer the purpose was to evaluate the prevalence of HPV over time and in relation to clinical outcome. In addition we wanted to evaluate if EGFR or phosphorylated EGFR were useful as markers, together with HPV, to predict response to treatment. For hypopharyngeal cancer, the aim was to analyze the prevalence of HPV and if HPV was a risk factor for this tumor type. In the first paper, we found a 7‐fold increase in the incidence of HPV positive tonsillar cancer, between 1970 and 2006, in the County of Stockholm, highlighting HPV as the causative factor for the increased incidence of this tumor type. In addition we found a decline in the incidence of HPV negative tonsillar cancer. In the second paper, we found a high 5‐year disease specific survival for HPV positive tonsillar cancer (81%), as compared to 36% for patients with HPV negative tonsillar cancer. HPV E6 and/or HPV E7 RNA were present in 94% of the samples analyzed, demonstrating the involvement of HPV in carcinogenesis. In the third paper, we analyzed the presence of HPV in HNSCC from Greece and found that HPV is common in tonsillar carcinoma also from this country. In the fourth paper, the presence of HPV and overexpression of p16 in hypopharyngeal cancer from patients in Stockholm, was evaluated. Only 6% were HPV positive, indicating that HPV is not an important risk factor for this disease.   In the fifth paper, overexpression of EGFR and presence of phoshorylated EGFR in tonsillar cancer, were evaluated in relation to tumor HPV status and clinical outcome. We found a correlation between the presence of phosphorylated EGFR and HPV, but not between phosphorylated EGFR and clinical outcome, when HPV positive and negative tumors were evaluated separately. Our studies revealed HPV as a major factor behind the increased incidence of tonsillar cancer in the Stockholm area and an important prognostic factor for this disease, while HPV was not an important risk factor for hypopharyngeal cancer in this area. 

Very large phase shift of microwave signals in a 6 nm Hf x Zr 1− x O 2 ferroelectric at ±3 V

In this letter, we report for the first time very large phase shifts of microwaves in the 1–10 GHz range, in a 1 mm long gold coplanar interdigitated structure deposited over a 6 nm Hf x Zr1−x O2 ferroelectric grown directly on a high resistivity silicon substrate. The phase shift is larger than 60° at 1 GHz and 13° at 10 GHz at maximum applied DC voltages of ±3 V, which can be supplied by a simple commercial battery. In this way, we demonstrate experimentally that the new ferroelectrics based on HfO2 could play an important role in the future development of wireless communication systems for very low power applications

Tumor Infiltrating CD8+ and Foxp3+ Lymphocytes Correlate to Clinical Outcome and Human Papillomavirus (HPV) Status in Tonsillar Cancer

BACKGROUND: Human papillomavirus (HPV) is a causative factor for tonsillar squamous cell carcinoma (TSCC) and patients with HPV positive (HPV(+)) TSCC have a better clinical outcome than those with HPV negative (HPV(-)) TSCC. However, since not all patients with HPV(+) TSCC respond to treatment, additional biomarkers are needed together with HPV status to better predict response to therapy and to individualize treatment. For this purpose, we examined whether the number of tumor infiltrating cytotoxic and regulatory T-cells in TSCC correlated to HPV status and to clinical outcome. METHODS: Formalin fixed paraffin embedded TSCC, previously analysed for HPV DNA, derived from 83 patients, were divided into four groups depending on the HPV status of the tumor and clinical outcome. Tumors were stained by immunohistochemistry and evaluated for the number of infiltrating cytotoxic (CD8(+)) and regulatory (Foxp3(+)) T-cells. RESULTS: A high CD8(+) T-cell infiltration was significantly positively correlated to a good clinical outcome in both patients with HPV(+) and HPV(-) TSCC patients. Similarly, a high CD8(+)/Foxp3(+) TIL ratio was correlated to a 3-year disease free survival. Furthermore, HPV(+) TSCC had in comparison to HPV(-) TSCC, higher numbers of infiltrating CD8(+) and Foxp3(+) T-cells. CONCLUSIONS: In conclusion, a positive correlation between a high number of infiltrating CD8(+) cells and clinical outcome indicates that CD8(+) cells may contribute to a beneficial clinical outcome in TSCC patients, and may potentially serve as a biomarker. Likewise, the CD8(+)/Foxp3(+)cell ratio can potentially be used for the same purpose

Oxygen-vacancy induced ferroelectricity in nitrogen-doped nickel oxide

This paper reports the onset of ferroelectricity in NiO by breaking the crystallographic symmetry with oxygen vacancies created by N doping. Nitrogen-doped NiO was grown at room temperature by RF sputtering of Ni target in Ar–O2–N2 plasma on silicon and fused silica substrates. The impact of the nitrogen doping of NiO on microstructural, optical, and electrical properties has been investigated. According to x-ray diffraction investigations, by increasing the N doping level in NiO, a transition from (002) to a (111) preferential orientation for the cubic NiO phase was observed, as well as a lattice strain relaxation, that is usually ascribed to structural defect formation in crystal. The x-ray diffraction pole figures the presence of a distorted cubic structure in NiO and supports the Rietveld refinement findings related to the strain, which pointed out that nitrogen doping fosters lattice imperfections formation. These findings were found to be in agreement with our far-infrared measurements that revealed that upon nitrogen doping a structural distortion of the NiO cubic phase appears. X-ray photo-emission spectroscopy measurements reveal the presence of oxygen vacancies in the NiO film following nitrogen doping. Evidence of ferro-electricity in nitrogen-doped NiO thin films has been provided by using the well-established Sawyer–Tower method. The results reported here provide the first insights on oxygen-vacancy induced ferroelectricity in nitrogen-doped nickel oxide thin films

Transparent all-oxide hybrid NiON/TiO2 heterostructure for optoelectronic applications

Nickel oxide (NiO) is a p-type oxide and nitrogen is one of the dopants used for modifying its properties. Until now, nitrogen-doped NiO has shown inferior optical and electrical properties than those of pure NiO. In this work, we present nitrogen-doped NiO (NiO:N) thin films with enhanced properties compared to those of the undoped NiO thin film. The NiO:N films were grown at room temperature by sputtering using a plasma containing 50% Ar and 50% (O2 + N2) gases. The undoped NiO film was oxygen-rich, single-phase cubic NiO, having a transmittance of less than 20%. Upon doping with nitrogen, the films became more transparent (around 65%), had a wide direct band gap (up to 3.67 eV) and showed clear evidence of indirect band gap, 2.50–2.72 eV, depending on %(O2-N2) in plasma. The changes in the properties of the films such as structural disorder, energy band gap, Urbach states and resistivity were correlated with the incorporation of nitrogen in their structure. The optimum NiO:N film was used to form a diode with spin-coated, mesoporous on top of a compact, TiO2 film. The hybrid NiO:N/TiO2 heterojunction was transparent showing good output characteristics, as deduced using both I-V and Cheung’s methods, which were further improved upon thermal treatment. Transparent NiO:N films can be realized for all-oxide flexible optoelectronic devices

An assessment of sputtered nitrogen-doped nickel oxide for all-oxide transparent optoelectronic applications: The case of hybrid NiO:N/TiO2 heterostructure

ransition metal oxides present a unique category of materials due to their versatile optical, electrical and mechanical properties. Nickel oxide (NiO) is an intrinsic p-type oxide semiconductor. P-NiO with controllable and reproducible physico-chemical properties, if combined with transparency and low temperature (low-T) fabrication processes, can be fully exploited in many transparent and/or flexible devices for applications, like energy management (production, manipulation, storage), sensing, wearable and health care electronics, etc. Reproducibility, transparency and low-T fabrication processes of p-type NiO are the motivation of this work. Nitrogen is one of the dopants used for modifying the properties of NiO. Until now, nitrogen-doped NiO, has shown inferior properties than those of pure NiO. In this work, we present nitrogen-doped NiO (NiO:N) thin films with enhanced properties compared to those of the undoped NiO. The NiO:N films were grown by sputtering on room-temperature substrates in plasma containing 50% Ar and 50% (O2+N2) gases. The undoped NiO film was oxygen-rich, single-phase cubic NiO, having transmittance less than 20%. Upon doping with nitrogen, the films became more transparent (around 65%), had a wide direct band gap (up to 3.67 eV) and showed clear evidence of indirect band gap, 2.50-2.72 eV, depending on %(O2-N2) in plasma. The changes in the properties of the films such as structural disorder, energy band gap, Urbach states and resistivity were correlated with the incorporation of nitrogen in their structure. The optimum NiO:N film was used to form a diode with spin-coated, mesoporous on top of a compact, TiO2 film. The hybrid NiO:N/TiO2 heterojunction was transparent showing good output characteristics, as deduced using both I-V and Cheung’s methods. The diode’s transparency and characteristics were further enhanced upon thermal treatment and this was attributed to improved NiO:N properties with annealing. Transparent NiO:N films can be realized for all-oxide flexible optoelectronic devices

Human Papillomavirus (HPV) 16 E6 Variants in Tonsillar Cancer in Comparison to Those in Cervical Cancer in Stockholm, Sweden

Background: Human papillomavirus (HPV), especially HPV16, is associated with the development of both cervical and tonsillar cancer and intratype variants in the amino acid sequence of the HPV16 E6 oncoprotein have been demonstrated to be associated with viral persistence and cancer lesions. For this reason the presence of HPV16 E6 variants in tonsillar squamous cell carcinoma (TSCC) in cervical cancer (CC), as well as in cervical samples (CS), were explored. Methods: HPV16 E6 was sequenced in 108 TSCC and 52 CC samples from patients diagnosed 2000–2008 in the County of Stockholm, and in 51 CS from young women attending a youth health center in Stockholm. Results: The rare E6 variant R10G was relatively frequent (19%) in TSCC, absent in CC and infrequent (4%) in CS, while the well-known L83V variant was common in TSCC (40%), CC (31%), and CS (29%). The difference for R10G was significant between TSCC and CC (p = 0.0003), as well as between TSCC and CS (p = 0.009). The HPV16 European phylogenetic lineage and its derivatives dominated in all samples (.90%). Conclusion: The relatively high frequency of the R10G variant in TSCC, as compared to what has been found in CC both in the present study as well as in several other studies in different countries, may indicate a difference between TSCC and CC with regard to tumor induction and development. Alternatively, there could be differences with regard to the oral an

Congenital Nonprofound Bilateral Sensorineural Hearing Loss in Children: Comprehensive Characterization of Auditory Function and Hearing Aid Benefit

A prospective cross-sectional design was used to characterize congenital bilateral sensorineural hearing loss (SNHL). The underlying material of >30,000 consecutively screened newborns comprised 11 subjects with nonprofound, alleged nonsyndromic, SNHL. Comprehensive audiological testing was performed at ≈11 years of age. Results showed symmetrical sigmoid-like median pure-tone thresholds (PTTs) reaching 50–60 dB HL. The congenital SNHL revealed recruitment, increased upward spread of masking, distortion product otoacoustic emission (DPOAE) dependent on PTT (≤60 dB HL), reduced auditory brainstem response (ABR) amplitude, and normal magnetic resonance imaging. Unaided recognition of speech in spatially separate competing speech (SCS) deteriorated with increasing uncomfortable loudness level (UCL), plausibly linked to reduced afferent signals. Most subjects demonstrated hearing aid (HA) benefit in a demanding laboratory listening situation. Questionnaires revealed HA benefit in real-world listening situations. This functional characterization should be important for the outline of clinical guidelines. The distinct relationship between DPOAE and PTT, up to the theoretical limit of cochlear amplification, and the low ABR amplitude remain to be elucidated. The significant relation between UCL and SCS has implications for HA-fitting. The fitting of HAs based on causes, mechanisms, and functional characterization of the SNHL may be an individualized intervention approach and deserves future research

Low-voltage phase shifters based on HfxZr1-xO2 ferroelectrics integrated with phased antenna arrays

In this paper, we present the design, fabrication and microwave experimental characterisation of a ferroelectric phase shifter, which is integrated with a 2-element antenna array to achieve beam-steering capabilities at very low voltages of ±1 V. The phase shifter consists of an interdigitated metallic capacitor deposited on a Zr-doped ferroelectric hafnium dioxide (Hf x Zr 1-x O 2 ) thin film, directly grown on high-resistivity Silicon (HR Si). The phase shifter shows a maximum phase shift of 53.74° at 2.55 GHz, sweeping the DC voltage between -1 V and +1 V. The miniaturised phased array is in the form of two gold patch antennas, phase shifters and additional circuitry, all integrated on HfxZr 1-x O 2 /HR Si 4-inch wafer. The radiation beam at 2.55 GHz is steered with 25° when the 7-nm-thick ferroelectric is biased with ±1 V. These new microwave devices represent a step forward in the realisation of low-voltage tunable microwave components for the upcoming 5G technology