Benefit of chemotherapy as part of treatment for HPV DNA-positive but p16-negative squamous cell carcinoma of the oropharynx

BACKGROUND: To determine (a) the cause of an improvement in survival from oropharyngeal squamous cell carcinoma (OSCC) in South East Scotland and (b) whether this improvement was human papillomavirus (HPV) and p16 subtype-dependent. METHODS: Clinicopathological characteristics and outcome data for patients referred with OSCC from 1999 to 2001 (Cohort-1) and 2003 to 2005 (Cohort-2) were obtained. Molecular HPV detection and immunohistochemistry for p16 were performed from paraffin blocks. RESULTS: Cohort-1 and Cohort-2 contained 118 and 136 patients, respectively. Kaplan–Meier analysis revealed significantly improved survival in Cohort-2 (P<0.0001). Sub-classification according to HPV and p16 status revealed no improvement in survival in Class-I (HPV−ve/p16−ve; 47 patients) or Class-III (HPV+ve/p16+ve; 77 patients). However in Class-II (HPV+ve/p16−ve; 56 patients) an increase in 5-year cause-specific survival from 36% in Cohort-1 to 73% in Cohort-2 was detected (P=0.0001). Proportional hazards analysis of 217 patients treated radically demonstrated that significant variables were p16 (P<0.0001), N stage (P=0.0006) and cohort (P=0.0024). Removing cohort from the variables offered to the model showed that, whereas p16 (P<0.0001) and N stage (P=0.0016) remain significant, chemotherapy (P=0.0163) and T stage (P=0.0139) are now significant. This suggests that much of the cohort effect is due to the higher use of chemotherapy in the second cohort. CONCLUSION: These data suggest that HPV+ve/p16−ve patients constitute a separate subclass of OSCC who may particularly benefit from chemotherapy. They imply that p16 status cannot be considered a surrogate for HPV status, and those trials to de-escalate treatment in HPV+ve OSCC should take p16 status into account

Preparation of Aluminum Metal Matrix Composite with Novel In situ Ceramic Composite Particulates, Developed from Waste Colliery Shale Material

A novel method is adapted to prepare an in situ ceramic composite from waste colliery shale (CS) material. Heat treatment of the shale material, in a plasma reactor and/or in a high temperature furnace at 1673 K (1400 °C) under high vacuum (10−6 Torr), has enabled in situ conversion of SiO2 to SiC in the vicinity of carbon and Al2O3 present in the shale material. The composite has the chemical constituents, SiC-Al2O3-C, as established by XRD/EDX analysis. Particle sizes of the composite range between 50 nm and 200 μm. The shape of the particles vary, presumably rod to spherical shape, distributed preferably in the region of grain boundaries. The CS composite so produced is added to aluminum melt to produce Al-CS composite (12 vol. pct). For comparison of properties, the aluminum metal matrix composite (AMCs) is made with Al2O3 particulates (15 vol. pct) with size <200 μm. The heat-treated Al-CS composite has shown better mechanical properties compared to the Al-Al2O3 composite. The ductility and toughness of the Al-CS composite are greater than that of the Al-Al2O3 composite. Fractographs revealed fine sheared dimples in the Al-CS composite, whereas the same of the Al-Al2O3 composite showed an appearance of cleavage-type facets. Abrasion and frictional behavior of both the composites have been compared. The findings lead to the conclusion that the in situ composite developed from the colliery shale waste material has a good future for its use in AMCs