Clinical Usefulness of Cervicogram as a Primary Screening Test for Cervical Neoplasia

The purpose of this study is to evaluate the clinical usefulness of the cervicogram as a primary screening test for cervical neoplasia. A total of 294 women who had undergone a cervicogram and a Pap test between January and July 2003, were selected. The diagnostic accuracy of the Pap test, cervicogram, and the Pap test combined with a cervicogram were compared with the histopathologic diagnosis. Among 294 women, the Pap test was negative in 130 cases and positive in 164 cases. Among patients with positive Pap test, cervicogram were negative in 101 cases (61.6%) and positive in 63 cases (38.4%). The diagnostic accuracy between cervicogram with positive Pap test and histology was as follows; sensitivity 44.9%, specificity 78.3%, positive predictive value 84.1%, negative predictive value 32.7%, false positive rate 15.9%, and false negative rate 67.3%. Although the adjunctive use of cervicogram with the Pap test in the initial screening of cervical neoplasia showed a higher specificity and higher positive predictive value compared to the Pap test alone, consideration in terms of lower sensitivity, lower positive predictive value, higher false positive rate and cost-effectiveness should be given in lieu of clinically applying cervicogram with the pap test as an initial screening test

Safety and preliminary efficacy data of a novel Casein Kinase 2 (CK2) peptide inhibitor administered intralesionally at four dose levels in patients with cervical malignancies

<p>Abstract</p> <p>Background</p> <p>Cervical cancer is now considered the second leading cause of death among women worldwide, and its incidence has reached alarming levels, especially in developing countries. Similarly, high grade squamous intraepithelial lesion (HSIL), the precursor stage for cervical cancer, represents a growing health problem among younger women as the HSIL management regimes that have been developed are not fully effective. From the etiological point of view, the presence of Human Papillomavirus (HPV) has been demonstrated to play a crucial role for developing cervical malignancies, and viral DNA has been detected in 99.7% of cervical tumors at the later stages. CIGB-300 is a novel cyclic synthetic peptide that induces apoptosis in malignant cells and elicits antitumor activity in cancer animal models. CIGB-300 impairs the Casein Kinase (CK2) phosphorylation, by targeting the substrate's phosphoaceptor domain. Based on the perspectives of CIGB-300 to treat cancer, this "first-in-human" study investigated its safety and tolerability in patients with cervical malignancies.</p> <p>Methods</p> <p>Thirty-one women with colposcopically and histologically diagnosed microinvasive or pre-invasive cervical cancer were enrolled in a dose escalating study. CIGB-300 was administered sequentially at 14, 70, 245 and 490 mg by intralesional injections during 5 consecutive days to groups of 7 – 10 patients. Toxicity was monitored daily until fifteen days after the end of treatment, when patients underwent conization. Digital colposcopy, histology, and HPV status were also evaluated.</p> <p>Results</p> <p>No maximum-tolerated dose or dose-limiting toxicity was achieved. The most frequent local events were pain, bleeding, hematoma and erythema at the injection site. The systemic adverse events were rash, facial edema, itching, hot flashes, and localized cramps. 75% of the patients experienced a significant lesion reduction at colposcopy and 19% exhibited full histological regression. HPV DNA was negative in 48% of the previously positive patients. Long term follow-up did not reveal recurrences or adverse events.</p> <p>Conclusion</p> <p>CIGB 300 was safe and well tolerated. This is the first clinical trial where a drug has been used to target the CK2 phosphoaceptor domain providing an early proof-of-principle of a possible clinical benefit.</p

A methodological framework to distinguish spectrum effects from spectrum biases and to assess diagnostic and screening test accuracy for patient populations: Application to the Papanicolaou cervical cancer smear test

<p>Abstract</p> <p>Background</p> <p>A spectrum effect was defined as differences in the sensitivity or specificity of a diagnostic test according to the patient's characteristics or disease features. A spectrum effect can lead to a spectrum bias when subgroup variations in sensitivity or specificity also affect the likelihood ratios and thus post-test probabilities. We propose and illustrate a methodological framework to distinguish spectrum effects from spectrum biases.</p> <p>Methods</p> <p>Data were collected for 1781 women having had a cervical smear test and colposcopy followed by biopsy if abnormalities were detected (the reference standard). Logistic models were constructed to evaluate both the sensitivity and specificity, and the likelihood ratios, of the test and to identify factors independently affecting the test's characteristics.</p> <p>Results</p> <p>For both tests, human papillomavirus test, study setting and age affected sensitivity or specificity of the smear test (spectrum effect), but only human papillomavirus test and study setting modified the likelihood ratios (spectrum bias) for clinical reading, whereas only human papillomavirus test and age modified the likelihood ratios (spectrum bias) for "optimized" interpretation.</p> <p>Conclusion</p> <p>Fitting sensitivity, specificity and likelihood ratios simultaneously allows the identification of covariates that independently affect diagnostic or screening test results and distinguishes spectrum effect from spectrum bias. We recommend this approach for the development of new tests, and for reporting test accuracy for different patient populations.</p

Quantifying the effect of hiking disturbance on American pika (Ochotona princeps) foraging behaviour

An animal's need to balance energy intake with predator avoidance results in trade-offs predicted by optimum foraging theory. These trade-offs may include reducing foraging activity if 1) perception of predation risk is high or 2) abiotic conditions are suboptimal for foraging. Human disturbances such as hikers can influence an animal's perception of predation risk, yet little is known about how hiking affects the foraging behaviour of species in the alpine zone. American pikas (Ochotona princeps) are small, food-hoarding mammals whose foraging ability is restricted by heat. If pikas' ability to forage is further decreased by hiking disturbance it could negatively impact their survival due to reduced food storage. To quantify the effect of hikers on foraging time, I evaluated multiple hypotheses of risk avoidance by simulating disturbance events for 48 pikas in Glacier National Park, BC. I assessed pikas' response to hikers using four indicators of risk behaviour: alert distance (DA), flight initiation distance (DF), exit delay (TE) and delay in return to forage (TR). To test if temperature or distance to trail was more influential to pikas' foraging activity, I conducted behavioural observations on 17 pikas. All simulated disturbance events elicited anti-predator response behaviours in foraging pikas, reducing time available to forage and increasing time spent alert and vigilant. Distance to trail was an important predictor of TE and TR. Pikas near trails (100 m away from trails, which lost an average of 13.2 (SE=1.7, n=16) minutes of foraging time per disturbance event. Temperature, not distance to trail, was the strongest predictor of pikas' foraging activity over a 4-6 hour period. This suggests that human disturbance may be partially mitigated by pikas' behavioural adaptation at less frequented sites. Monitoring pika populations near and away from trails would be well-advised given projected trends in warming climate and potential increases in hiking traffic.Science, Faculty ofZoology, Department ofGraduat