Low levels of serum vitamins A and E in blood and subsequent risk for cervical cancer: Interaction with HPV seropositivity

Nutritional factors have been associated with risk of cervical cancer, but it is unclear whether the associations are of etiological significance or s econdary to human papillomavirus (HPV) exposure. A delineation of this ques tion requires a prospective study with invasive cancer as the end point. We conducted a nested case-control study in Finland and Sweden within a joint cohort of 405,000 women followed up for, on average, 4 years. Blood sample s from 38 prospective cases of invasive cervical cancer diagnosed between 1 985 and 1994 and 116 controls matched for age, country, and sample storage time were available for the study. Levels of retinol or unoxidized alpha-to copherol in the blood were not risk factors for cervical cancer. However, j oint-effect analysis of low levels of retinol disclosed statistically signi ficant (p = 0.023) synergistic (more than multiplicative) interaction with HPV (HPV16, HPV18, or HPV33) seropositivity (observed relative risk = 2.6, 95% confidence interval = 0.7-8.8, expected relative risk = 0.3). Retinol m ight act as an effect modifier of the HPV-associated risk for cervical canc er; exposed women may require adequate levels for immunologic surveillance of HPV.