The conventional direct referral to colposcopy of persistent borderline or mildly dyskaryotic (BMD) smears in cervical cancer screening leads to considerable unnecessary referrals and associated anxiety and costs. This may be improved by including testing for oncogenic human papillomavirus (HPV) in the triage. We assessed costs and side effects (referrals, treatments and time in follow-up) for 3 possible HPV triage strategies (immediate HPV testing, a 6-month delay in HPV testing, a 2-stage combination of both) and compared them with the conventional strategy. The assessments are based on recent Dutch data from various national databases and trials. We estimated that the referral rate could be reduced by 49, 58 and 58% with immediate, delayed and 2-stage HPV testing, respectively. As a consequence, the average length of follow-up, as well as average costs, also decrease. Therefore, we advocate including HPV testing before referring to colposcopy. Among the 3 HPV strategies, analysis of additional aspects favors implementation of immediate HPV testing. ' 2007 Wiley-Liss, Inc.Key words: borderline and mild dyskaryosis; human papillomavirus; triage; cost; side effects Cytology-based cervical cancer screening prevents deaths by treating preinvasive (cervical intraepithelial neoplasia, CIN) and early invasive disease. Low-grade abnormalities described as borderline and mild dyskaryosis (BMD) are the most common type of cytologic abnormalities, ranging in frequency from below 2% in the Netherlands to above 6% in Finland.1 In several countries, it is currently recommended to follow-up these women with a Pap smear in 6 months. [2][3][4] Women are then referred for a colposcopy if the BMD abnormality does not normalize. 3 In the Netherlands, about one third of the women with BMD primary screening smears is eventually referred, 1 most often because of BMD persistence and less often because of cytological progression.
5This diagnostic policy of following-up BMD smears induces a considerable amount of side effects in terms of a high number of referrals and a long follow-up period with associated costs and psychologic consequences. About 60-90% of women with BMD persistence have no high-grade lesion that needs to be treated.
6-13The burden on women and the health care could be reduced if the subgroup at high risk for a significant lesion were identified.It has been consistently shown in the literature that detection of an infection with one of the high-risk human papillomavirus types (HPV) can be used for a risk stratification of women with lowgrade abnormal smears.14,15 An infection with HPV is a necessary factor in the development of invasive cervical cancer. 16 Because no histological progression is seen in women who spontaneously clear the HPV infection, 17 women without a detectable HPV infection do not need further follow-up. That could be the case in 40-60% of women with persistent BMD smears.7-13 The discussion about the optimal strategy and time points of incorporating HPV testing into triage of women with BMD smear...