European Federation for Colposcopy and Institut national du Cancer (INCA).

Background: CA125 is a high molecular weight glycoprotein, which is expressed by a large proportion of epithelial ovarian cancers. The sensitivity and specificity of CA125 are poor and there are no guidelines produced by the Royal College of Pathologists or the Association of Clinical Biochemists to aid clinicians and laboratories in its most appropriate use. Aim: To identify the patient population having a CA125 measurement and to determine its contribution to individual patient management. Methods: A retrospective case note audit looking at patients who had a CA125 measurement performed between April 2000 and April 2002. Results: The study comprised 799 patients; 751 (94%) were female and 48 (6%) male; 221 (29%) females and 22 (46%) males had an abnormal result. CA125 was mainly used to investigate a wide range of signs and symptoms, and few tests were for follow up or screening of ovarian cancer. In female patients having a CA125 for suspicion of malignancy/ovarian cancer, only 39 (20%) of the abnormal results were caused by ovarian cancer. False positive results were largely caused by another malignancy (48 cases; 26%), benign ovarian disease (26 cases; 14%), and benign gynaecological conditions, particularly leiomyomas (18 cases; 9%). The specificity of CA125 for ovarian cancer increased with concentrations .1000 kU/ litre. Conclusions: These results confirm the high false positive rate and poor sensitivity and specificity associated with CA125. The substantial inappropriate usage of CA125 has led to results that are useless to the clinician, have cost implications, and add to patient anxiety and clinical uncertainty.

BackgroundThe human papillomavirus (HPV) vaccine is recommended for adolescent girls in many European countries, however there is huge variation in vaccine uptake. Methods A mixed methods systematic review to ascertain the level of HPV and HPV vaccine knowledge that exists among European adolescents. Two electronic databases, Ovid Medline and PsychInfo, were searched from origin to September 2014. Meta-analysis was performed for the two primary outcome measures ('have you heard of HPV?' and 'have you heard of the HPV vaccine?'), assessing for the correlation between gender and knowledge. This was supplemented with meta-synthesis for the remaining associations and secondary outcomes. Results 18 papers were included in the final review. Overall European adolescents had poor understanding of basic HPV and HPV vaccine knowledge. Meta-analysis identified that female adolescents are more likely to have heard of HPV (n=2598/5028 girls versus n=1033/3464 boys; OR 2.73, 95% CI 1.86-3.99) and the HPV vaccine (n=1154/2556 girls versus n=392/2074 boys; OR 5.64, 95% CI 2.43-13.07), compared to males. Age, higher education and a positive vaccination status were also associated with increased awareness. There was limited appreciation of more detailed HPV knowledge and uncertainty existed regarding the level of protection offered by the vaccine and the need for cervical screening post vaccination. Conclusions The delivery of HPV education to European adolescents needs to be re-evaluated, since at present there appears to be significant deficiencies in their basic knowledge and understanding of the subject. Increasing HPV knowledge will empower adolescents to make informed choices regarding participation with HPV related cancer prevention health strategies.

Background The colposcopy-directed punch biopsy is widely used in the management of women with abnormal cervical cytology; however, its accuracy compared with definitive histology from an excision biopsy is not well established.Objectives To assess the accuracy of the colposcopy-directed punch biopsy to diagnose high-grade cervical intraepithelial neoplasia (CIN) by performing a systematic review and meta-analysis.Search strategy A systematic search of MEDLINE, EMBASE and the Cochrane Library was performed.Selection criteria Articles that compared the colposcopically directed cervical punch biopsy with definitive histology from an excisional cervical biopsy or hysterectomy.Data collection and analysis Random effects and hierarchical summary receiver operating characteristic regression models were used to compute the pooled sensitivity and specificity applying different test cut-offs for outcomes of high-grade CIN.Main results Thirty-two papers comprising 7873 paired punch/ definitive histology results were identified. The pooled sensitivity for a punch biopsy defined as test cut-off CIN1+ to diagnose CIN2+ disease was 91.3% (95% CI 85.3-94.9%) and the specificity was 24.6% (95% CI 16.0-35.9%). In most of the studies, the majority of enrolled women had positive punch biopsies. Pooling of the four studies where the excision biopsy was performed immediately after the punch biopsy, and where the rate of positive punch biopsies was considerably lower, yielded a sensitivity of 81.4% and specificity of 63.3%.Author's conclusion The observed high sensitivity of the punch biopsy derived from all studies is probably the result of verification bias.

No abstract

Introduction A shift in focus towards risk stratification and survivorship in early stage endometrial cancer (EC) has led to the replacement of hospital follow‐up (HFU) with patient‐initiated follow‐up (PIFU) schemes. Methods A mixed methods study was undertaken prospectively to investigate utility and patient satisfaction with a newly introduced PIFU scheme. Results Two hundred and twenty‐eight women were enrolled onto PIFU in the first 18 months, median age 65 years (range 42–90 years). Twenty‐four (10.5%) women were non‐British White ethnicity. Forty‐five women contacted the Clinical Nurse Specialist (CNS) at least once (19.7%), the primary reason being vaginal bleeding/discharge (42%). Contact was greater in first six months on the scheme compared to the second 6 months, and women who made contact were significantly younger than those who did not (57 years vs. 65 years, p < 0.001). Conclusions PIFU appears to be well received by the majority of women. Although many of the CNS contacts were due to physical symptoms, a number were for psychological support or reassurance. Younger women had greater CNS contact indicating that they may benefit from a greater level support. Patient feedback of the PIFU scheme was positive, with many women reporting that it enabled them to have more control over their own health.

ACCEPTED MANUSCRIPT ABSTRACTCervical cancer is the fourth most common cancer in women worldwide (WHO, 2016). In many developed countries the incidence of cervical cancer has been significantly reduced by the introduction of organised screening programmes however, in the UK, a fall in screening coverage is becoming a cause for concern. Much research attention has been afforded to younger women but age stratified mortality and incidence data suggest that older women's screening attendance is also worthy of study. This paper provides a review of current evidence concerning the psycho-social influences that older women experience when Highlights There has been a lack of research on older women and cervical screening  This is at odds with age stratified incidence and mortality data  Embarrassment and logistical issues may deter older women from cervical screening  Psychological, emotional and physical age related changes can also play a role  Further research to enable informed decision-making among older women is required ACCEPTED MANUSCRIPT

Real-time quantitative RT-PCR (qRT-PCR) is a powerful technique used for the relative quantification of target genes, using reference (housekeeping) genes for normalization to ensure the generation of accurate and robust data. A systematic examination of the suitability of endogenous reference genes for gene expression studies in endometrial cancer tissues is absent. The aims of this study were therefore to identify and evaluate from the thirty-two possible reference genes from a TaqMan(®) array panel their suitability as an internal control gene. The mathematical software packages geNorm qBasePLUS identified Pumilio homolog 1 (Drosophila) (PUM1), ubiquitin C (UBC), phosphoglycerate kinase (PGK1), mitochondrial ribosomal protein L19 (MRPL19) and peptidylpropyl isomerase A (cyclophilin A) (PPIA) as the best reference gene combination, whilst NormFinder identified MRPL19 as the best single reference gene, with importin 8 (IPO8) and PPIA being the best combination of two reference genes. BestKeeper ranked MRPL19 as the most stably expressed gene. In addition, the study was validated by examining the relative expression of a test gene, which encodes the cannabinoid receptor 1 (CB1). A significant difference in CB1 mRNA expression between malignant and normal endometrium using MRPL19, PPIA, and IP08 in combination was observed. The use of MRPL19, IPO8 and PPIA was identified as the best reference gene combination for the normalization of gene expression levels in endometrial carcinoma. This study demonstrates that the arbitrary selection of endogenous control reference genes for normalization in qRT-PCR studies of endometrial carcinoma, without validation, risks the production of inaccurate data and should therefore be discouraged.