Study to determine concordance between high-risk human papilloma virus DNA detection in self collected first voided urine samples and health-care worker collected cervical samples in a subset of women with proven histopathological precancerous and cancerous lesions of the cervix

Objective: The objective of our study was to assess whether urinary samples for human papilloma virus (HPV) detection are a good predictive marker of cervical cancerous and precancerous lesions, by comparing against results from cervical scrapings as the gold standard test. Materials and Methods: The study is a hospital-based cross-sectional study wherein symptomatic women were screened at the colposcopy clinic. Paired samples-cervical scrapings/washings and urine samples were tested for hr-HPV for women who were found to harbor premalignant and malignant lesions of the cervix in histopathological lesions, by multiplex real-time polymerase chain reaction and HPV genotyping. Diagnostic accuracy was tested by calculating concordance with Cohen's kappa with hr-HPV detection in cervical samples as the gold standard. Results: A total of 295 patients undergoing colposcopy were recruited in the study, out of which 54 had histopathological-proven premalignant and malignant lesions of the cervix. Overall, positivity rate in urinary samples for both HPV 16 and 18 combined is 64.81%, whereas for cervical samples is 68.51%. HPV 16 was seen in 30 (55.5%) and 32 (59.3%) cervical and urinary samples, respectively, whereas HPV 18 was seen in 7 (12.9%) and 6 (11.1%) samples, respectively. There was substantial concordance between the cervical samples and first-void urinary samples results with Cohen's k: 0.6988 (95% confidence interval: From 0.507 to 0.891). There was 85.96% agreement among all the tests that were performed with only 14.04% disagreement. Conclusions: The study showed that HPV DNA detection from the urine and cervical samples showed significant agreeability for the detection of precancerous and cancerous lesions of the cervix among women with abnormal histology results. Thus, urinary sampling can be done as a potential replacement for cervical sampling methods with the added benefit as it can be used in females reluctant to provide cervical samples, if there is no availability of skilled workforce for collecting samples, for mass screening, and for the follow-up of vaccination programs

Tryptophan–NAD+ pathway metabolites as putative biomarkers and predictors of peroxisome proliferation

The present study was designed to provide further information about the relevance of raised urinary levels of N-methylnicotinamide (NMN), and/or its metabolites N-methyl-4-pyridone-3-carboxamide (4PY) and N-methyl-2-pyridone-3- carboxamide (2PY), to peroxisome proliferation by dosing rats with known peroxisome proliferator-activated receptor α (PPARα) ligands [fenofibrate, diethylhexylphthalate (DEHP) and long-chain fatty acids (LCFA)] and other compounds believed to modulate lipid metabolism via PPARα-independent mechanisms (simvastatin, hydrazine and chlorpromazine). Urinary NMN was correlated with standard markers of peroxisome proliferation and serum lipid parameters with the aim of establishing whether urinary NMN could be used as a biomarker for peroxisome proliferation in the rat. Data from this study were also used to validate a previously constructed multivariate statistical model of peroxisome proliferation (PP) in the rat. The predictive model, based on H nuclear magnetic resonance (NMR) spectroscopy of urine, uses spectral patterns of NMN, 4PY and other endogenous metabolites to predict hepatocellular peroxisome count. Each treatment induced pharmacological (serum lipid) effects characteristic of their class, but only fenofibrate, DEHP and simvastatin increased peroxisome number and raised urinary NMN, 2PY and 4PY, with simvastatin having only a transient effect on the latter. These compounds also reduced mRNA expression for aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase, EC 4.1.1.45), the enzyme believed to be involved in modulating the flux of tryptophan through this pathway, with decreasing order of potency, fenofibrate (-10.39-fold) >DEHP (-3.09-fold) >simvastatin (-1.84-fold). Of the other treatments, only LCFA influenced mRNA expression of ACMSDase (-3.62-fold reduction) and quinolinate phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) (-2.42-fold) without any change in urinary NMN excretion. Although there were no correlations between urinary NMN concentration and serum lipid parameters, NMN did correlate with peroxisome count (r =0.63) and acyl-CoA oxidase activity (r =0.61). These correlations were biased by the large response to fenofibrate compared to the other treatments; nevertheless the data do indicate a relationship between the tryptophan-NAD pathway and PPARα-dependent pathways, making this metabolite a potentially useful biomarker to detect PP. In order to strengthen the observed link between the metabolites associated with the tryptophan-NAD pathway and more accurately predict PP, other urinary metabolites were included in a predictive statistical model. This statistical model was found to predict the observed PP in 26/27 instances using a pre-determined threshold of 2-fold mean control peroxisome count. The model also predicted a time-dependent increase in peroxisome count for the fenofibrate group, which is important when considering the use of such modelling to predict the onset and progression of PP prior to its observation in samples taken at autopsy