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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...

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ObjectivesDNA methylation analysis of cancer-related genes is a promising tool for HPV-positive women to identify those with cervical (pre)cancer (CIN3+) in need of treatment. However, clinical performance of methylation markers can be influenced by the sample type utilized. We describe a multiplex quantitative methylation-specific PCR that targets FAM19A4 and mir124-2 loci, to detect CIN3+ using both HPV-positive lavage- and brush self-samples.MethodsWe determined methylation thresholds for clinical classification using HPV-positive training sets comprising lavage self-samples of 182 women (including 40 with CIN3+) and brush self-samples of 224 women (including 61 with CIN3+). Subsequently, independent HPV-positive validation sets of 389 lavage self-samples (including 78 with CIN3+), and 254 brush self-samples (including 72 with CIN3+) were tested using the preset thresholds. Furthermore, the clinical performance of combined methylation analysis and HPV16/18 genotyping was determined.ResultsTraining set analysis revealed similar FAM19A4 and mir124-2 thresholds for both self-sample types to yield highest CIN3+ sensitivity at 70% specificity. Validation set analysis resulted in a CIN3+ sensitivity of 70.5% (95%CI: 60.4–80.6) at a specificity of 67.8% (95%CI: 62.7–73.0) for lavage self-samples, and a CIN3+ sensitivity of 69.4% (95%CI: 58.8–80.1) at a 76.4% (95%CI: 70.2–82.6) specificity for brush self-samples. In combination with HPV16/18 genotyping, CIN3+ sensitivity and specificity were 88.5% (95%CI: 81.4–95.6) and 46.0% (95%CI: 40.4–51.5) for lavage self-samples, and 84.7% (95%CI: 76.4–93.0) and 54.9% (95%CI: 47.7–62.2) for brush self-samples.ConclusionsFAM19A4/mir124-2 methylation analysis performs equally well in HPV-positive lavage- and brush self-samples to identify women with CIN3+. In combination with HPV16/18 genotyping, significantly higher CIN3+ sensitivities are obtained, at decreased specificity.

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