Bereavement Is Associated with an Increased Risk of HPV Infection and Cervical Cancer: An Epidemiological Study in Sweden.

Grief over the loss of a family member may cause physical and mental illness, but an association between bereavement and cancer risk has not been established. Based on the Swedish National Cervical Screening Register (1969-2011) including 14,011,269 smears from 2,466,107 women, we conducted two nested case-control studies to examine the associations of bereavement (i.e., loss of a family member due to death) with abnormal cytology (390,310 first abnormal and 1,951,319 normal smears) and in situ/invasive cervical cancer (75,128 case and 375,640 control women), both individually matched on year of birth and screening adherence. Among 1,696 of the control women, we further investigated bereavement in association with human papillomavirus (HPV) infection, both HPV16 and other HPV types. Bereavement was consistently associated with a 4% to 9% increased risk for first abnormal cytology, in situ and invasive cervical cancer (all P < 0.02). The associations became stronger when multiple losses, loss of child, sibling or spouse, and loss due to unnatural cause were analyzed separately (P for trend or difference < 0.0001), and for women with high screening adherence (P for difference < 0.05). Among 1,696 women who had not developed cervical cancer, we further investigated the link between bereavement and HPV infection. Bereavement was associated with a 62% increased risk of HPV16 infection, high viral load, and recurrent infection, and was also more strongly associated with HPV infections designated as high-risk compared with low-risk determinants of cervical carcinogenesis. Collectively, our findings demonstrate that bereavement is associated with an increased risk of developing cervical cancer. Further, they suggest that this association may be attributed to stress-induced oncogenic HPV infections.