of histomorphologic diagnoses with special reference to the kappa statistic. APMIS 97: [689][690][691][692][693][694][695][696][697][698] 1989.Systems for classification and grading used in pathology should ideally be biologically meaningful and at least be reproducible from one pathologist to another. A statistical method to evaluate reproducibility (non-chance agreement) for several observers using nominal or ordinal categories has been developed and refined over the past few decadesthe kappa statistic. A high level of observed agreement among different pathologists can either signify a high level of reproducibility, if agreement by chance is low, or express a low level of reproducibility, if agreement by chance is almost as high as the observed agreement. Therefore, the observed agreement says nothing in itself, unless it is low. The kappa value, however, indicates how much better the observers are compared to a throw of the dice, and therefore gives the real credit to the agreement which was found. We have developed a user-friendly computer program for calculating inter-and intra-observer agreement of 2 or more observers. By calculating associations between different categories and different observers, the statistic furthermore obtains a function close to the parameter of accuracy. We recommend the use of the above method before a set of nominal or rank scale parameters are used for deciding prognosis and treatment of patients. By submitting a diskette the computer program will be available at no cost.

BackgroundStudies comparing self-samples and clinician-collected samples for high-risk human papillomavirus (HPV) detection using clinically validated PCR-based HPV DNA assays are limited. We measured the concordance of HPV detection between home-based self-sampling and general practitioner (GP) sampling using the Cobas 4800 HPV DNA test and studied women’s accept of home-based self-sampling.MethodsPaired GP-collected samples and cervico-vaginal self-samples were obtained from 213 women aged 30–59 years diagnosed with ASC-US within the cervical cancer screening program. After undergoing cervical cytology at their GP, the women collected a self-sample with the Evalyn Brush at home and completed a questionnaire. Both samples were HPV-tested using the Cobas 4800 test. Histology results were available for those who tested HPV positive in GP-collected samples.ResultsWe observed good concordance for HPV detection between self-samples and GP-collected samples (κ: 0.70, 95% CI: 0.58–0.81). No underlying CIN2+ cases were missed by self-sampling. Women evaluated that self-sampling was easy (97.2%, 95% CI: 93.9–98.9%) and comfortable (94.8%, 95% CI: 90.9–97.4%).ConclusionsHome-based self-sampling using the Evalyn Brush and the Cobas 4800 test is an applicable and reliable alternative to GP-sampling.

BackgroundCervical cancer screening participation remains insufficient in most countries. Our aim was to evaluate whether offering a HPV self-sampling kit, either mailed directly to the woman’s home or using timely opt-in procedures for ordering the kit, increased screening participation compared with a standard second reminder.MethodsIn this randomized, controlled effectiveness trial, 9791 Danish women aged 30–64 who were due to receive the second reminder were equally randomized to either: 1) direct mailing of a second reminder and a self-sampling kit (directly mailed group); 2) mailing of a second reminder that offered a self-sampling kit to be ordered by e-mail, text message, phone, or webpage (opt-in group); or 3) mailing of a second reminder to attend regular cytology screening (control group). In an intention-to-treat analysis, we estimated the participation rate at 180 days post intervention, by returning a self-sample or attending regular cytology screening. We calculated the proportion of women with a positive HPV self-sample who attended for cervical cytology triage at the general practitioner within 90 days.ResultsParticipation was significantly higher in the directly mailed group (38.0%) and in the opt-in group (30.9%) than in the control group (25.2%) (participation difference (PD): 12.8%, 95% CI: 10.6–15.0% and PD: 5.7%, 95% CI: 3.5–7.9%, respectively). Within 90 days, 107 women (90.7%, 95% CI: 83.9–95.3%) with a HPV-positive self-sample attended follow-up.ConclusionsOffering the opportunity of HPV self-sampling as an alternative to regular cytology screening increased participation; the direct mailing strategy was the most effective invitation strategy. A high compliance with follow-up was seen.Trial registrationCurrent Controlled Trials NCT02680262. Registered 10 February 2016.

BackgroundThe effectiveness of cervical cancer screening programs is challenged by suboptimal participation and coverage. Offering cervico-vaginal self-sampling for human papillomavirus testing (HPV self-sampling) to non-participants can increase screening participation. However, the effect varies substantially among studies, especially depending on the approach used to offer HPV self-sampling. The present trial evaluates the effect on participation in an organized screening program of a HPV self-sampling kit mailed directly to the home of the woman or mailed to the woman’s home on demand only, compared with the standard second reminder for regular screening.Methods/designThe CHOiCE trial is a parallel, randomized, controlled, open-label trial. It will include 9327 women aged 30–64 years who are living in the Central Denmark Region and who have not participated in cervical cancer screening after an invitation and one reminder. The women will be equally randomized into three arms: 1) Directly mailed a second reminder including a HPV self-sampling kit; 2) Mailed a second reminder offering a HPV self-sampling kit, to be ordered by e-mail, text message, phone, or through a webpage; and 3) Mailed a second reminder for a practitioner-collected sample (control group). The primary outcome will be the proportion of women in the intervention groups who participate by returning their HPV self-sampling kit or have a practitioner-collected sample compared with the proportion of women who have a practitioner-collected sample in the control group at 90 and 180 days after mail out of the second reminders. Per-protocol and intention-to-treat analyses will be performed. The secondary outcome will be the proportion of women with a positive HPV self-collected sample who attend follow-up testing at 30, 60, or 90 days after mail out of the results.DiscussionThe CHOiCE trial will provide strong and important evidence allowing us to determine if and how HPV self-sampling can be used to increase participation in cervical cancer screening. This trial therefore has the potential to improve prevention and reduce the number of deaths caused by cervical cancer.Trial registrationCurrent Controlled Trials NCT02680262. Registered 10 February 2016.

In this study, we aimed to provide molecular evidence of HPV latency in humans and discuss potential challenges of conducting studies on latency. We analyzed the entire cervix of two women who underwent hysterectomy unrelated to cervical abnormality. The cervices were sectioned into 242 and 186 sets respectively, and each set was tested separately for HPV using the SPF10-PCR-DEIA-LiPA25 system. To identify whether there was any evidence of transforming or productive infection, we used the biomarkers E4 and P16 INK4a to stain slides immediately adjacent to HPV-positive sections. HPV was detected in both cervices. In patient 1, 1/242 sets was positive for HPV31. In patient 2, 13/186 sets were positive for HPV18 and 1/186 was positive for HPV53. The infection was very focal in both patients, and there was no sign of a transforming or productive infection, as evaluated by the markers E4 and P16 INK4a . Had we only analyzed one set from each block, the probability of detecting the infection would have been 32.3% and 2%, respectively.Our findings support the idea that HPV may be able to establish latency in the human cervix; however, the risk associated with a latent HPV infection remains unclear.