Psychological stress and cervical cancer mortality

Results of a study by Swedish investigators suggest that psychological stress may have a negative effect on survival of patients with cervical cancer. The findings, published in Cancer Research, also point to the year before and after diagnosis as the period when the association is most concerning.

For the case-control study, the authors identified 4,245 patients who were newly diagnosed with invasive cervical cancer from 2002 to 2011, using the national Swedish Cancer Register. Medical charts were used to collect information on the FIGO stage of the tumors, histology, mode of detection, primary treatment, and adjuvant therapy. A Charlson’s comorbidity index was generated by linking patients to the Swedish Patient Register, which includes information on hospital discharge records and hospital-based outpatient specialist visits. 

The investigators looked at a composite of three psychiatric disorders in the patients with cervical cancer-stress reaction and adjustment disorders, depression, and anxiety disorder-as a proxy for severe psychologic distress. The exposure they chose was newly diagnosed disorders from 1 year before cervical cancer diagnosis onward. Highly stressful life events included death or severe illness of a family member, divorce, and being between jobs.

All deaths in the cohort during follow-up were identified from the Causes of Death Register, in which there is a 92% agreement between death and medical records for cancer as an underlying cause of death. 

Of the patients in the cohort, 92% (1,797) were exposed to stress-related disorders and 37.4% to stressful life events in the year before cancer diagnosis onward. Of this subgroup, 48% experienced the disorders or events within 1 year before or after their cervical cancer diagnosis. There was no difference with and without psychologic distress in terms of FIGO stage, histologic type of cancer detection pattern. Palliative treatment, however, was more common in patients with a stress-related disorder in the year before cancer diagnosis.

Risk of cancer-specific mortality was higher in patients who experienced psychologic distress from 1 year before cancer diagnosis onward (HR 1.33; 95% CI, 1.14-1.54) versus patients who were unexposed to that distress. The relationship was still statistically significant after adjustment for clinical characteristics (HR 1.26; 95% CI, 1.08-1.46). The risk was particularly elevated in individuals exposed to stress-related disorders (HR 1.55; 95% CI, 1.20-1.99), and also elevated in those exposed to stressful life events (HR 1.20; 95% CI, 1.02-1.41).

A higher risk of cancer-specific mortality was associated with stressful life events only when they occurred within the year before or after the cervical cancer diagnosis, whereas a similar elevation in risk was seen in association with stress-related disorders regardless of the time of diagnosis.

The authors said theirs is the first study to show that associations between stress and cancer-specific mortality are independent of known prognostic indicators, tumor characteristics, mode of diagnosis, and treatment. They theorize, based on results from experimental studies, that psychologic distress modulates tumor growth through dysregulation of oncogenes, angiogenesis, inflammation, and host immune responses operated by the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Decreased cellular immunity and immunosurveillance also may result when chronic stress reduces T-cell-proliferative response.

“If verified in independent populations,” the investigators concluded, “these findings may lend support to a specific and continuous role of psychologic distress in the etiology/pathogenesis of cervical cancer. Furthermore, given that 42% of patients with cervical cancer experienced a stress-related disorder or stressful life event along the disease course, psychologic intervention may be considered as an integral component in cervical cancer care.”