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Women not attending cervical screening programs are at increased risk of cervical cancer. We investigated in these nonresponders to what extent offering self-sampling devices for cervicovaginal brushes for high-risk human papillomavirus (hrHPV) testing would induce participation and, if so, what the yield of precursor (i.e. CIN2 or worse) lesions following self-sampling would be. In addition, we assessed screening history of participants and costs per detected high-grade CIN2 or worse ("CIN2+") lesion in comparison to the regular program in the Netherlands. Nonresponders received a device for hrHPV testing (self-sampling group, n=2,546) or an extra recall for conventional cytology (control group, n=284). The percentage of self-sampling responders were compared with responders in the recall group. hrHPV positive self-sampling responders were invited for cytology and colposcopy. CIN2+ yield and costs per detected CIN2+ were evaluated. Active response was higher in the self-sampling than in the control group (34.2 vs. 17.6%; p<0.001). hrHPV positive self-sampling responders were less likely to have a prior screening history than screening participants (p<0.001), indicating that they are regular nonresponders. hrHPV prevalence was similar (8.0 vs. 6.8%; p=0.11), but CIN2+ yield was higher in self-sampling responders compared to screening participants (1.67 vs. 0.97%; OR=2.93, 95% CI 1.48-5.80; p=0.0013). Costs per CIN2+ lesion detected via self-sampling were in the same range as those calculated for conventional cytological screening (euro 8,836 vs. euro 7,599). Offering self-sampling for hrHPV testing in nonresponders is an attractive adjunct to effectively increase population coverage of screening without the adverse effect of markedly increased costs per detected CIN2+ lesion.

According to the current guidelines in most western countries, women treated for cervical intraepithelial neoplasia grade 3 (CIN 3) are followed for at least 2 years after treatment by cytology.High-risk human papillomavirus (hrHPV) infections are necessary for the development and maintenance of CIN 3. HrHPV testing could be used to improve monitoring of women treated for CIN 3. This has prompted numerous studies for the implementation of hrHPV testing in monitoring of women treated for CIN 3. Included in this review are 20 studies, published between 1996 and 2003, comparing hrHPV testing with either resection margins or cervical cytology to predict recurrent/residual disease, and 11 of them could be used in a meta-analysis. In the meta-analysis of the 11 studies, the negative predictive value (NPV) for recurrent/residual disease of hrHPV testing was 98% (95% CI 97-99%), that of resection margins 91% (95% CI 87-94%), and that of cervical cytology 93% (95% CI 90-95%). When hrHPV testing was performed in conjunction with cytology, the sensitivity was 96% (95% CI 89-99%), specificity was 81% (95% CI 77-84%), the associated positive predictive value (PPV) was 46% (95% CI 38-54%), and the NPV was 99% (95% CI 98-100%). Combined hrHPV and cytology testing yielded the best test characteristics. We propose to include hrHPV testing in conjunction with cytology for monitoring women treated for CIN 3. Some follow-up visits for women testing negative for both hrHPV and cytology can be skipped. In western countries, this could mean that for women double negative at 6 months, retesting at 12 months should be skipped while keeping the 24-month follow-up visit.

Background: A shifted balance between T helper 1 (Th1)-type and Th2-type cytokines has been hypothesised in cervical dysplasia Aims: To evaluate possible deregulation of the cytokine network by estimating the expression of peripheral cytokines in different stages of cervical disease and in relation to the presence or absence of high risk human papillomavirus (HR-HPV). Methods: Twenty one HR-HPV positive women with high grade cervical intraepithelial neoplasia (CIN II-III) and 12 patients with invasive cervical carcinoma formed the study groups. Two control groups consisted of 10 HR-HPV positive and 11 HR-HPV negative women without CIN. Differences in leucocyte subgroups were evaluated by a differential leucocyte count. Plasma concentrations of tumour necrosis factor a (TNFa), TNFa receptors TNFRI and TNFRII, interferon c (IFNc), interleukin 2 (IL-2), IL-12, IL-4, and IL-10 were determined by enzyme linked immunosorbent assays. Results: Leucocyte counts in patients with CIN III and carcinoma were significantly higher than in controls. Plasma IFNc concentrations were significantly lower in patients with CIN III and carcinoma than in women with CIN II or controls. Plasma concentrations of IL-12, IL-2, IL-4, and TNFa did not differ significantly between groups, but significantly lower plasma concentrations of TNFRII were found in CIN III and carcinoma compared with CIN II. IL-10 was detected with increased frequency in the plasma of patients with CIN III and carcinoma. Conclusions: These results indicate that a shift to a Th2-type cytokine pattern during the carcinogenesis of cervical cancer occurs in women with CIN III lesions.

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