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We determined whether testing of self-collected vaginal swabs for human papillomavirus (HPV) DNA can be used to screen for cervical disease within internal medicine outpatient clinics.In this prospective study, 560 patients visiting two referral outpatient clinics for internal medicine were asked to take an HPV self-sample. Acceptability of self sampling, HPV prevalence and cervical intraepithelial neoplasia (CIN) detection rate were evaluated.435 women (78%) performed HPV self-sampling; 1.5% considered self-sampling to be difficult. 134 women (31%) tested positive for high-risk type of HPV. There were significant differences between HPV-positive and -negative women with respect to the following: mean age (42 versus 46 years), number of women aged <16 years at first coitus (35% versus 23%) and history of drug abuse (8.3% versus 2.6%). Colposcopy could be performed for 70 HPV positive women: CIN 1–3 was identified in 24%. Two of 52 women with HPV-negative results undergoing colposcopy had biopsy-confirmed CIN 1. Test performance for detection of CIN 2–3 after correction for verification bias: sensitivity, 100%; specificity, 71%; negative predictive value, 100%; positive predictive value, 10%. HPV persistence was associated with a 5.7-fold risk of CIN 2–3 detection at follow-up.Self-assessment for HPV DNA is an easy, feasible and well-accepted method for HPV testing and for cervical cancer screening in internal medicine outpatient clinics.