Abstract
To evaluate the risk factors associated with persistence of human papillomaviruses (HPV) types 16, 18, and 33 in the normal cervix, a prospective study was carried out in Belgium of 323 women without cytological evidence of cervical intraepithelial neoplasia. Demographic and clinical data were obtained by interview, and HPV DNA was assayed in cervical‐swab specimens using the Fast Multiplex Polymerase Chain Reactionbased screening and confirmatory tests. A multivariable linear regression model was constructed using four well‐known risk factors: the use of an oral contraceptive which is either triphasic, or monophasic and containing ethynylestradiol in association with either norethysterone, or levonorgestrel, or lynestrenol, or gestoden, or estrogenic and containing estriol (P = 8 × 10^−6^) a positive history of genital herpes simplex virus (HSV) infection (P = l0^−4^), an age inferior or equal to 30 years (P = 0.012), and cigarette smoking (P = 0.020). Crude and adjusted relative risks were calculated for each HPV persistence predictor. The data and the results of the molecular biology of high‐risk genital HPVs are consistent with the hypothesis that the use of an oral contraceptive containing simultaneously and continuously both a potent estrogen and a high activity progestative is necessary to enhance significantly HPV transcription. These observations are also consistent with the hypothesis that the oral contraceptives and HSV genital infection are responsible for HPV persistence in the normal cervix but not for HPV‐induced cervical transformation. The relatively weak correlation found for cigarette smoking may be explained by the very moderate induction effect of phorbol esters on HPV expression, in comparison with their important transforming effect on virus‐infected cells, and thus by the limited number of HPV‐infected women in our study. The fourth predictor probably represents several other risk factors associated with young age such as a high number of sexual partners. © 1992 Wiley‐Liss, Inc.