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Participants 28 073 women who had not responded to two invitations to the regular cervical screening programme: 27 792 women were assigned to the self sampling group and invited to submit a self collected cervicovaginal sample for HPV testing; 281 were assigned to the recall control group and received a second reinvitation for conventional cytology. Intervention Women with a positive result on the high risk HPV test on their self sample material were referred to their general practitioner. Women with abnormal results on cytology were referred for colposcopy. Women with normal results on cytology were re-evaluated after one year by cytology and high risk HPV testing and referred for colposcopy if either result was positive. Main outcome measures Attendance rate in both groups and yield of cervical intraepithelial neoplasia grade II/III or worse (≥CIN II/≥CIN III) in self sampling responders. Results The compliance rate in the self sampling group was significantly higher than in the control group (crude 26.6% v 16.4%, P<0.001; adjusted 27.5% v 16.6%, P<0.001). The number of detected ≥CIN II and ≥CIN III lesions in self sampling responders was 99 (1.3%) and 76 (1.0%), respectively. Self sampling responders who had not participated in the previous round of screening (43%) had increased relative risks of ≥CIN II (2.04, 95% confidence interval 1.27 to 3.28) and ≥CIN III (2.28, 1.31 to 3.96) compared with self sampling women who had been screened in the previous round (57%). ConclusionsOffering self sampling by sending a device for collecting cervicovaginal specimens for high risk HPV testing to women who did not attend regular screening is a feasible and effective method of increasing coverage in a screening programme. The response rate and the yield of high grade lesions support implementation of this method for such women. Trial registration ISRCTN45527158.

Cytological cervical screening is rather inefficient because of relatively high proportions of false negative and false positive smears. To evaluate the efficiency of high-risk human papillomavirus (hrHPV) testing, by GP5؉/6؉ PCR-enzyme immunoassay (EIA), in conjunction with cytology (Intervention Group) to that of the classical cytology (Control Group), we initiated the Population Based Screening Study Amsterdam (POBASCAM). POBASCAM is a population-based randomized controlled trial for implementation of hrHPV testing in cervical screening. The outcome measure is the proportion of histologically confirmed >CIN3 lesions in each study arm up to and including the next screening round after 5 years. We present the design, methods and baseline data of POBASCAM. When, in the next 5 years, the follow-up will be completed, the data obtained will be used in model studies, including a cost-effectiveness study, to advise the Dutch Ministry of Public Health in deciding whether cervical screening should be based on combined hrHPV and cytology testing instead of cytology alone. Between January 1999 and September 2002, 44,102 women (mean age ‫؍‬ 42.8 years; range ‫؍‬ 29 -61) that participated in the regular Dutch screening program were included in our study. In the Intervention Group the distribution of cytology and hrHPV by cytology class was as follows: normal cytology 96.6% (3.6% hrHPV positive); borderline and mild dyskaryosis (BMD) 2.5% (34.6% hrHPV positive); and moderate dyskaryosis or worse (>BMD) 0.8% (88.3% hrHPV positive), i.e., 0.4% moderate dyskaryosis (82.9% hrHPV positive), 0.3% severe dyskaryosis (92.5% hrHPV positive), 0.1% carcinoma in situ (95.2% hrHPV positive), <0.1% suspected for invasive cancer (hrHPV positive 100.0%). In the Control Group 96.5% of the women had normal cytology, 2.4% BMD and 0.8% >BMD, i.e., 0.4% moderate dyskaryosis, 0.3% severe dyskaryosis, 0.1% carcinoma in situ, <0.1% suspected for invasive cancer. The presence of hrHPV was age-dependent, decreasing from 12.0% at 29 -33 years to 2.4% at 59 -61 years. Among women with a positive hrHPV test, the prevalence of BMD was age-dependent ranging from 20.2% at 29 -33 years to 7.8% at 54 -58 years. In contrast, the risk of >BMD of 13.7% among women with a positive hrHPV test was not age-dependent. Our study indicates that large-scale hrHPV testing by GP5؉/6؉ PCR-EIA in the setting of population-based cervical screening is practically feasible, is accepted by both participating women and general practitioners and yields highly reproducible results.

This review elaborates on the accuracy and feasibility of human papillomavirus (HPV) self-sampling, i.e., offering self-sampling of (cervico-)vaginal cell material by women themselves in nonclinical settings for high-risk HPV (hrHPV) detection in the laboratory, for cervical screening. To that end a bibliographic database search (PubMed) was performed to identify studies (published between January 1992 and January 2012) that compared clinical accuracy of HPV testing on self-sampled material with that of cytology or HPV testing on clinician-taken samples, and studies comparing response to offering HPV self-sampling with a recall invitation. Overall, hrHPV testing on self-samples appeared to be at least as, if not more, sensitive for cervical intraepithelial neoplasia grade 2 or worse (CIN21) as cytology on clinician-obtained cervical samples, though often less specific. In most studies, hrHPV testing on self-and clinician-sampled specimens is similarly accurate with respect to CIN21 detection. Variations in clinical performance likely reflect the use of different combinations of collection devices and HPV tests. Because it is known that underscreened women are at increased risk of cervical cancer, targeting non-attendees of the screening program could improve the effectiveness of cervical screening. In developed countries offering self-sampling has shown to be superior to a recall invitation for cytology in re-attracting original non-attendees into the screening program. Additionally, self-testing has shown to facilitate access to cervical screening for women in low resource areas. This updated review of the literature suggests that HPV self-sampling could be an additional strategy that can improve screening performance compared to current cytology-based call-recall programs.For years, cervical scrapes taken by clinicians constituted the basis for cervical cancer screening via either conventional or liquid-based cytology (LBC).1,2 However, several randomized controlled trials have shown that, given its higher sensitivity for cervical intraepithelial neoplasia grade 2 or worse (CIN2þ), high-risk human papillomavirus (hrHPV) testing on clinician-taken cervical scrapes provides a better protection against cervical cancer than cytology.3-5 Therefore, HPV testing is likely to become an important primary cervical screening tool in the near future.Another item that got much attention in the last couple of years involves the use of self-collected (cervico-) vaginal material as an alternative for clinician-collected cervical scrapes for screening. Swabs, brushes, tampons or lavage devices have been used as self-collection devices. Surveys in which participants were asked for collection preference have shown that women prefer self-collection over clinician-collection, with time and place of sampling, privacy and ease of sampling being the mentioned advantages of self-sampling. Only a small number of women were reluctant because they either did not understand the provided instructions or were insecure if they had used the s...