Validation of high-risk HPV tests for primary cervical screening.

From a clinical point of view, testing for a broad spectrum of high-risk human papillomavirus (hrHPV) is only useful when a positive hrHPV test result is informative about the presence of high-grade cervical intraepithelial neoplasia or cervical cancer (CIN 2 or worse). Two hrHPV tests, i.e. HC2 and GP5+/6+, have shown in large clinical trials that they perform better in the detection of CIN 2+/CIN 3+ lesions than cytology and thus have been clinically validated. Consequently these tests are now considered as alternative screening tools for cytology in cervical screening. Candidate hrHPV tests to be used for cervical screening should have a similar balance between sensitivity and specificity for CIN 2+ lesions as these two clinically validated hrHPV tests in order to prevent redundant or excessive follow-up procedures for women with transient hrHPV infections or hrHPV-positive women without cervical lesions. The data from these large prospective clinical studies can be used to set standards for the clinical performance and characteristics of the candidate hrHPV test. To prevent costly validation trajects of candidate hrHPV tests and based on the available data from large clinical studies we demonstrate how guidelines for hrHPV test requirements and guidelines for clinical validation of candidate hrHPV tests have been developed, and how these guidelines should be used in cervical screening. It is expected that the use of these guidelines will facilitate implementation of hrHPV testing in primary cervical screening.

The effects of perceived stress, traits, mood states, and stressful daily events on salivary cortisol.

This study examined the effects of perceived stress and related individual characteristics, mood states, and stressful daily events on salivary cortisol levels. Forty-one "high stress" and 46 "low stress" subjects were selected on the basis of Perceived Stress Scale scores from a sample of male, white collar workers. Subjects completed Experience Sampling self-reports and collected saliva samples 10 times a day over 5 consecutive days. Multilevel analysis revealed that trait anxiety and depression, but not perceived stress, were associated with small but statistically significant cortisol elevation. No effects on cortisol were found for recent life events, chronic difficulties, trait anger, or psychosomatic symptoms. Distress, as reflected by the mood states Negative Affect and Agitation, was associated with higher cortisol levels, whereas Positive Affect had no statistically significant effect. Stressful daily events were associated with increased cortisol secretion, the magnitude of the effect depending on whether the event was still ongoing and on how frequently a similar kind of event had occurred previously. Although perceived stress, anxiety, and depression did not increase cortisol reactivity to daily events, we found evidence for reduced habituation to recurrent events in subjects scoring high on these traits. Mood appeared to play a mediating role in the relationship between stressful events and cortisol secretion. These results suggest that negative affectivity is not just a confounder but is related to elevated cortisol secretion during normal daily activities. The finding that even minor events and fluctuations in mood states were associated with increased adrenocortical activity points to a possible mechanism linking subjective experience to health outcomes.

Individual differences in cortisol responses to a laboratory speech task and their relationship to responses to stressful daily events.

A Stress Inducing Speech Task was used to investigate the contribution of perceived stress, individual traits, and current mood states to individual differences in salivary cortisol responses. Additionally, we examined the correspondence between laboratory baseline cortisol levels and overall levels in daily life, and between cortisol responses to the speech task and a measure of stress reactivity to stressful events in daily life. Forty-two 'high stress' and forty-five 'low stress' white-collar males completed the speech task and an Experience Sampling study, in which stressful daily events and cortisol levels were monitored for five days. No association was found between perceived stress, trait anxiety, anger, depression, psychosomatic symptoms, coping style or personality and cortisol responses to the speech task. Negative mood state at baseline was associated with higher cortisol levels at baseline just before, and just after, the speech. Laboratory and field cortisol levels were moderately correlated, but no association was found between laboratory and field response measures. Laboratory baseline levels, but not responses to the speech task, were significant predictors of field cortisol levels.