METHODS: Blood samples from 78 knowlesi malaria patients were used. Forty-eight of the samples were from Peninsular Malaysia, and 30 were from Malaysia Borneo. The genomic DNA of the samples was extracted and used as template for the PCR amplification of the PkγRII. The PCR product was cloned and sequenced. The sequences obtained were analysed for genetic diversity and natural selection using MEGA6 and DnaSP (version 5.10.00) programmes. Genetic differentiation between the PkγRII of Peninsular Malaysia and North Borneo isolates was estimated using the Wright's FST fixation index in DnaSP (version 5.10.00). Haplotype analysis was carried out using the Median-Joining approach in NETWORK (version 4.6.1.3).
RESULTS: A total of 78 PkγRII sequences was obtained. Comparative analysis showed that the PkγRII have similar range of haplotype (Hd) and nucleotide diversity (π) with that of PkDBPαRII. Other similarities between PkγRII and PkDBPαRII include undergoing purifying (negative) selection, geographical clustering of haplotypes, and high inter-population genetic differentiation (FST index). The main differences between PkγRII and PkDBPαRII include length polymorphism and no departure from neutrality (as measured by Tajima's D statistics) in the PkγRII.
CONCLUSION: Despite the biological difference between PkγRII and PkDBPαRII, both generally have similar genetic diversity level, natural selection, geographical haplotype clustering and inter-population genetic differentiation index.
METHODS: EGFR GCN was examined by in situ hybridization (ISH) in biopsies from 78 patients with OPMD and 92 patients with early-stage (stages I and II) OSCC. EGFR ISH signals were scored by two pathologists and a category assigned by consensus. The data were correlated with patient demographics and clinical outcomes.
RESULTS: OPMD with abnormal EGFR GCN were more likely to undergo malignant transformation than diploid cases. EGFR genomic gain was detected in a quarter of early-stage OSCC, but did not correlate with clinical outcomes.
CONCLUSION: These data suggest that abnormal EGFR GCN has clinical utility as a biomarker for the detection of OPMD destined to undergo malignant transformation. Prospective studies are required to verify this finding. It remains to be determined if EGFR GCN could be used to select patients for EGFR-targeted therapies.
IMPACT: Abnormal EGFR GCN is a potential biomarker for identifying OPMD that are at risk of malignant transformation. Cancer Epidemiol Biomarkers Prev; 25(6); 927-35. ©2016 AACR.
METHODS: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multi-centre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.
RESULTS: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.
CONCLUSIONS: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.
METHODS: From October 2012 to May 2013, prisoners housed in two distinct units (HIV-negative and HIV-positive) were approached to participate in the TB screening study. Consenting prisoners submitted two sputum samples that were examined using GeneXpert MTB/RIF, smear microscopy and liquid culture. Socio-demographic and clinical information was collected and correlates of active TB, defined as having either a positive GeneXpert MTB/RIF or culture results, were assessed using regression analyses.
RESULTS: Among the total of 559 prisoners, 442 (79.1%) had complete data; 28.7% were HIV-infected, 80.8% were men and the average age was 36.4 (SD 9.8) years. Overall, 34 (7.7%) had previously undiagnosed active TB, of whom 64.7% were unable to complete their TB treatment in prison due to insufficient time (<6 months) remaining in prison. Previously undiagnosed active TB was independently associated with older age groups (AOR 11.44 and 6.06 for age ≥ 50 and age 40-49 years, respectively) and with higher levels of immunosuppression (CD4 < 200 cells/ml) in HIV-infected prisoners (AOR 3.07, 95% CI 1.03-9.17).
CONCLUSIONS: The high prevalence of previously undiagnosed active TB in this prison highlights the inadequate performance of internationally recommended case-finding strategies and suggests that passive case-finding policies should be abandoned, especially in prison settings where HIV infection is prevalent. Moreover, partnerships between criminal justice and public health treatment systems are crucial to continue TB treatment after release.