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IntroductionThe clinical course of high-grade cervical intraepithelial neoplasia (CIN2/3) is characterised by a high spontaneous regression rate. Histological assessment is unable to differentiate between CIN2/3 lesions likely to regress and those likely to persist or progress. Most CIN2/3 lesions are treated by surgical excision, leading to overtreatment of a substantial proportion. In this prospective study, we evaluate the value of DNA methylation of host cell genes, which has shown to be particularly sensitive for the detection of advanced CIN2/3 and cervical cancer, in the prediction of regression or non-regression of CIN2/3 lesions.Methods and analysisThis is a multicentre observational longitudinal study with 24-month follow-up. Women referred for colposcopy with an abnormal cervical scrape, who have been diagnosed with CIN2/3 and a small cervical lesion (≤50% of cervix) will be asked to participate. Participants will be monitored by 6-monthly cytological and colposcopic examination. In case of clinical progression, participants will receive treatment and exit the study protocol. At baseline and during follow-up, self-sampled cervicovaginal brushes and cervical scrapes will be collected for high-risk human papillomavirus (HPV) testing andFAM19A4/miR124-2methylation analysis. A colposcopy-directed biopsy will be taken from all participants at the last follow-up visit. The primary study endpoint is regression or non-regression at the end of the study based on the histological diagnosis. Regression is defined as CIN1 or less. Non-regression is defined as CIN2 or worse. The secondary study endpoint is defined as HPV clearance (double-negative HPV test at two consecutive time-points). The association between methylation status and regression probability will be evaluated by means of χ2testing.Ethics and disseminationEthics approval was obtained in all participating clinics. Results of the main study will be submitted for publication in a peer-reviewed journal.Trial registration numberNTR6069; Pre-results

Clarifying the diagnosis of clinically suspected recurrence of cervical cancer can be challenging. The aim of this study was to investigate the clinical value of 18 F-FDG PET in this context. Methods: The medical records of a cohort of 40 18 F-FDG PET referrals in whom recurrence of cervical cancer was clinically suspected were reviewed. Two expert gynecologic oncologists assessed the level of pre-PET clinical doubt, quality of pre-PET work-up, and impact of 18 F-FDG PET on diagnostic understanding and management using questionnaires. Results: In patients with clinically equivocal recurrence, 18 F-FDG PET had a sensitivity of 92% and a specificity of 93% (prevalence, 65%). Before 18 F-FDG PET, there was high disagreement about the adequacy of the conventional work-up (intraclass correlation coefficient [ICC], 0.25) and the presence of recurrence (ICC, 0.24). 18 F-FDG PET increased experts' confidence (median increase, 14% and 25%; P , 0.0001) and diagnostic agreement (from 68% to 98%; ICC, from 0.24 to 0.95). When 18 F-FDG PET was positive for recurrence, the median overall survival was 13 mo. For patients with negative 18 F-FDG PET findings, the median survival was not reached (log rank, 15.50, P 5 0.0001). When the treatment plan was categorized as local therapy, systemic therapy, and expectative management, 18 F-FDG PET changed the treatment plan in half of all cases. The 2 experts reported that 18 F-FDG PET led to a better diagnosis and a beneficial change in management in, respectively, 60% and 65% of cases. Conclusion: 18 F-FDG PET can help to clarify the diagnosis of clinically suspected recurrence of cervical cancer. In this patient population, 18 F-FDG PET had significant value in diagnostic understanding and management of recurrent cervical cancer, facilitating decision making and treatment planning. Therefore, 18 F-FDG PET should be part of the diagnostic work-up in detection of recurrent cervical cancer. The high positive predictive value of 18 F-FDG PET in these patients suggests that inclusion in intervention trials might be based on a positive 18 F-FDG PET scan.

We assessed the effect of increasing experience of a single surgeon (learning curve) in the laparoscopic staging procedure for women with early ovarian cancer and compared the results with the literature. We retrospectively analysed a total of 25 women with apparent early-stage ovarian cancer who underwent a laparoscopic staging procedure by the same surgeon. Three time periods, based on date of surgery, were compared with respect to operating time, amount of lymph nodes harvested and surgical outcome. There was no significant difference in operation time, estimated blood loss and hospital stay between the three periods. There was, however, a significant increase in the median number of pelvic and para-aortal lymph nodes harvested (group1 = 6.5, group 2 = 8.0 and group 3 = 21.0; P < 0.005). For the total period, median operation time was 235 min and median estimated blood loss was 100 ml. The median length of hospital stay was 4.0 days. Two intraoperative and two postoperative complications occurred. The upstaging rate was 32%. The mean interval between initial surgery and laparoscopic staging was 51.2 days. Mean duration of follow-up was 43 months, range (1–116 months). Five (20%) patients had recurrences, and two (8%) patients died of the disease. In conclusion, there is a significant learning curve for the laparoscopic full staging procedure in ovarian cancer. In our study this is mainly reflected in the amount of lymph nodes harvested and not in the total operating time.