Stress Disorders and Human Papillomavirus-Related Cancer Rates: A Population-Based Cohort Study in Denmark

Stress disorders are associated with immunosuppression, potentially reducing the ability to clear human papillomavirus (HPV) infections, leading to an increased risk of HPV-related cancers. We investigated the association between stress disorders and HPV-related cancers in Denmark.

Using population-based medical registries, we identified patients with an incident hospital-diagnosed stress disorder between 1 January 1995 and 31 December 2021 (acute stress reaction, posttraumatic stress disorder, adjustment disorder, and other/unspecified reactions to severe stress), matched them by age and sex to individuals without any stress disorder diagnoses in the general population (1:5 ratio), and identified subsequent HPV-related cancer diagnoses (cervical, anal, vulvar, vaginal, penile, base of tongue, tonsillar, oropharyngeal) through 2022. Follow-up began after a 1-year lag period and was censored at first HPV-related cancer, other cancer diagnosis, emigration, death, or end of study. Covariates were measured prior to stress disorder diagnosis or matching date. We used Cox proportional hazards regression to estimate the sex-stratified adjusted hazard ratio (aHR) and 95% confidence interval (CI) of any HPV-related cancer and specific HPV-related cancers, adjusting for potential confounders.

During a median follow-up of approximately 10 years, there were 755 cases of HPV-related cancer in the stress disorder cohort (n=242,828) and 2,820 cases in the comparison cohort. Women with diagnosed stress disorders were more likely to develop any HPV-related cancer (aHR=1.3, 95% CI: 1.1-1.4), while men with stress disorders had an elevated rate of anal cancer specifically (aHR=1.7, 95% CI: 1.0-2.9) than their counterparts without stress disorders. The association between stress disorders and HPV-related cancer increased with younger age at stress disorder diagnosis and with longer follow-up time.

Our results suggest an association between stress disorders and slightly elevated rates of HPV-related cancer, which strengthens with longer follow-up, underscoring the need to understand biological and behavioral pathways linking stress disorders to increased risk of HPV-related cancer.