Graduation Year

2013

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Epidemiology and Biostatistics

Major Professor

Anna R. Giuliano

Co-Major Professor

Aurora Sanchez-Anguiano

Keywords

behavioral, psychoneuroimmunology, sexually transmitted infection, sleep disturbance, virus

Abstract

Introduction: Mucosal human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) and is associated with genitals warts, anogenital cancers, and oropharyngeal cancers. Most sexually active persons will become infected with HPV at some point in their lives, however few will develop HPV-related diseases such as warts, lesions, or cancer as a result of the infection. It is unclear why a minority of individuals fail to clear HPV infection and develop clinical disease. Due to initial associations with cervical lesions, much research has focused on women. Th1 type immune responses have been associated with successful response to HPV infection. Factors such as psychological stress and sleep have been associated with immune function. Stress has been associated with cervical lesions, however no study has evaluated effects of stress or sleep on HPV infection. This research sought to examine the associations between perceived stress and sleep problems with HPV prevalence, incidence, and clearance among men.

Methods: Men were tested for 37 individual HPV genotypes every 6 months as part of a large natural history study. A total of 426 men were followed over 1 to 4 visits. Perceived stress was measured with a modified 4-item Perceived Stress Scale (PSS-4) assessing stress in the past six months and was dichotomized into high (scores in the 4th quartile) and low perceived stress. Self-reported sleep problems were measured by seven likert-scale items and categorized as high (4th quartile of sleep problems scores), moderate (second and third quartiles; reference group), and low (first quartile). Three HPV classifications were examined; men were categorized as positive for 'Any HPV' if they tested positive for any of the 37 HPV genotypes in the study protocol, men were categorized as positive for 'Oncogenic HPV' if they tested positive for any oncogenic HPV type, and men were categorized as positive for 'Non-oncogenic HPV' if they tested positive for any non-oncogenic HPV genotype.

In the prevalence analysis, men who had no detectable HPV infection with any of the 37 types were the reference group in all analyses. Prevalence ratios and 95% confidence intervals (95% CI) were calculated using Poisson regression with robust variance. For HPV clearance and incidence, Cox regression with the robust sandwich estimator was used to calculated hazard ratios and 95% confidence intervals.

Results: A total of 424 men had genotyping results available for the prevalence analysis. High perceived stress was significantly associated with higher prevalence of any HPV infection [PR =1.33 (95% CI: 1.06-1.68)] and oncogenic HPV infection [PR=1.53 (95% CI: 1.06-2.20)], adjusting for demographics, sexual behavior, and sleep problems. High self-reported sleep problems was significantly associated with higher prevalence of oncogenic HPV infection [PR=1.50 (95% CI:1.01-2.13)], adjusting for demographics, sexual behavior, and perceived stress.

Perceived stress and self-reported sleep problems were not associated with incidence of HPV infection. Perceived stress was not significantly associated with clearance of HPV infection overall. Among men 50 and older however, men with high stress were significantly less likely to clear any HPV infection than those with low stress adjusting for demographics, HR=0.09 (95% CI: 0.02-0.49). Compared to men with moderate sleep problems, those with high sleep problems were significantly less likely to clear an infection with any HPV type, HR=0.68 (95% CI: 0.49-0.94), or an oncogenic HPV type, HR=0.51 (95% CI: 0.28-0.94), after adjustment for demographics and perceived stress.

Discussion: This is the first study to examine associations between HPV infection with perceived stress and self-reported sleep problems. It is also the largest study to examine associations between these exposures and an infection outcome. Results suggest that perceived stress and self-reported sleep problems have independent effects on HPV. Evaluation of perceived stress, biological indicators of stress, objective measures of sleep, and measurement of immune parameters may aid in further elucidating how stress and sleep disturbance are related to HPV infection. Determination of modifiable factors that can influence HPV infection may aid in the prevention of adverse disease outcomes related to infection with this virus. Examining the impact of factors such as perceived stress and sleep problems on HPV infection may aid in risk stratification of patients and allow more targeted interventions among those most at risk for developing disease.

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