Working together to shape the endometrial cancer research agenda: The top ten unanswered research questions.

BACKGROUND: Endometrial cancer (EC) is the most common gynaecological cancer in developed nations and its incidence is rising. As a direct consequence, more women are dying from EC despite advances in care and improved survivorship. There is a lack of research activity and funding, as well as public awareness about EC. We sought to engage patients, carers and healthcare professionals to identify the most important unanswered research questions in EC. METHODOLOGY: The priority setting methodology was developed by the James Lind Alliance and involved four key stages: gathering research questions; checking these against existing evidence; interim prioritisation; and a final consensus meeting during which the top ten unanswered research questions were agreed using modified nominal group methodology. RESULTS: Our first online survey yielded 786 individual submissions from 413 respondents, of whom 211 were EC survivors or carers, and from which 202 unique unanswered research questions were generated. 253 individuals, including 108 EC survivors and carers, completed an online interim prioritisation survey. The resulting top 30 questions were ranked in a final consensus meeting. Our top ten spanned the breadth of patient experience of this disease and included developing personalised risk scoring, refining criteria for specialist referral, understanding the underlying biology of different types of EC, developing novel personalised treatment and prevention strategies, prognostic and predictive biomarkers, increasing public awareness and interventions for psychological issues. CONCLUSION: Having established the top ten unanswered research questions in EC, we hope this galvanises researchers, healthcare professionals and the public to collaborate, coordinate and invest in research to improve the lives of women affected by EC.

A prospective study of anal cancer screening in HIV-positive and negative MSM.

OBJECTIVE: The study sought to establish the feasibility and acceptability of anal screening among men MSM. DESIGN: Prospective cohort study. SETTING: Sexual health clinics in tertiary care. PATIENTS: Known HIV-positive and negative MSM who have anoreceptive intercourse. INTERVENTION: Anal screening with human papilloma virus (HPV) testing, liquid-based cytology and high-resolution anoscopy with biopsy of anoscopic abnormalities. Participants completed questionnaires at baseline and at 6 months. RESULTS: Anal HPV was highly prevalent in MSM (HIV-positive, 88% and HIV-negative, 78%). Despite the high prevalence of cytological abnormality in both HIV-positive (46.2%) and negative (35.0%) MSM, almost half of anal intraepithelial neoplasia (AIN) of all grades were associated with negative cytology. Anoscopically directed biopsies detected AIN3 or worse (AIN3+) in 14 of 203 (6.9%) of HIV-positive MSM and three of 81 (3.7%) HIV-negative MSM. The corresponding prevalence of AIN2+ was 26.6 and 20.9%, respectively. One case of AIN3 was detected at the second visit. Screening was considered to be highly acceptable by participants. CONCLUSION: The high prevalence of high-risk-HPV and frequency of false negative cytology in this study suggest that high-resolution anoscopy would have most clinical utility, as a primary screening tool for anal cancer in a high-risk group. The prevalence of AIN3+ in HIV-positive MSM lends support for a policy of screening this group, but the high prevalence of lower grade lesions which do not warrant immediate treatment and the limitations of treating high-grade lesions requires careful consideration in terms of a screening policy.

Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI).

BACKGROUND: Failure of implantation and conception may result from an inability of the blastocyst to escape from its outer coat, which is known as the zona pellucida. Artificial disruption of this coat is known as assisted hatching and has been proposed as a method for improving the success of assisted conception by facilitating embryo implantation. OBJECTIVES: To determine the effect of assisted hatching (AH) of embryos from assisted conception on live birth and multiple pregnancy rates.  SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (August 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (August 2012), MEDLINE (1966 to August 2012) and EMBASE (1980 to August 2012). SELECTION CRITERIA: Three authors identified and independently screened trials. We included randomised controlled trials (RCTs) of AH (mechanical, chemical or laser disruption of the zona pellucida prior to embryo replacement) versus no AH that reported live birth or clinical pregnancy. DATA COLLECTION AND ANALYSIS: Three authors independently performed quality assessments and data extraction. MAIN RESULTS: Thirty-one trials reported clinical pregnancy data, including 1992 clinical pregnancies in 5728 women. There was no significant difference in the odds of live birth in the AH group compared with the control group (9 RCTs; odds ratio (OR) 1.03, 95% confidence interval (CI) 0.85 to 1.26, moderate quality evidence), with no evidence of significant heterogeneity (P = 0.38) or inconsistency (I(2) = 6%). Analysis of the clinical pregnancy rates from the nine studies which reported live birth showed a non-significant result (OR 1.03, 95% CI 0.85 to 1.25 ).Analysis of all of the studies included in this update (31 RCTs) showed that the clinical pregnancy rate in women who underwent AH was slightly improved, but the level only just reached statistical significance (OR 1.13, 95% CI 1.01 to 1.27, moderate quality evidence). However, it is important to note that the heterogeneity for this combined analysis for clinical pregnancy rate was statistically significant (P = 0.001) and the I(2) was 49%. Subgroup analysis of women who had had a previous failed attempt at IVF found improved clinical pregnancy rates in the women undergoing AH compared with the women in the control group (9 RCTs, n = 1365; OR 1.42, 95% CI 1.11 to 1.81) with I(2) = 20%. Miscarriage rates per woman were similar in both groups (14 RCTs; OR 1.03, 95% CI 0.69 to 1.54, P = 0.90, moderate quality evidence). Multiple pregnancy rates per woman were significantly increased in women who were randomised to AH compared with women in the control groups (14 RCTs, 3447 women; OR 1.38, 95% CI 1.11 to 1.70, P = 0.004, low quality evidence). AUTHORS' CONCLUSIONS: This update has demonstrated that whilst assisted hatching (AH) does appear to offer a significantly increased chance of achieving a clinical pregnancy, the extent to which it may do so only just reaches statistical significance. The 'take home' baby rate was still not proven to be increased by AH. The included trials provided insufficient data to investigate the impact of AH on several important outcomes. Most trials still failed to report on live birth rates.

Colposcopy is not necessary to assess the risk to the cervix in HIV-positive women: an international cohort study of cervical pathology in HIV-1 positive women.

The objectives of this prospective multicentre international cohort study are to describe the characteristics of a cohort of HIV-1 positive women and determine the best management system by comparing cervical pathology according to results of cytology, colposcopy and human papillomavirus (HPV) testing at baseline and throughout follow-up. A. Cohorts of known HIV-positive women were recruited from 6 hospital-based European centres and a community-based South African centre. Following registration, women were reviewed every 6 months to undergo cervical surveillance including cytology, colposcopy, histopathology and HPV testing, using the HPV hybrid capture assay. Independent risk factors for the incidence of cytological abnormality and acquisition/clearance of HPV infection during follow up were identified. A total of 1,534 women were recruited, 400 of which were from South Africa. At baseline, among European women, 66% had normal cytology and half were HPV negative and among South African women, 45% had normal cytology and one third (32%) were HPV negative. The sensitivity of cytology (>/=ASCUS) matched with that of colposcopy to detect CIN2+. Rate of detection of high grade CIN at 2 years was similar in European and South African women (11 and 9.3%, respectively). Cytology and HPV testing alone were each sufficiently sensitive as a screening test at 2 yearly intervals. Our data confirm the high prevalence of low-grade cytological abnormalities and high-risk HPV infection. Cytology appears to be sufficient for cervical surveillance, with HPV testing being less specific with poor positive predictive value. There appears to be no additional benefit from routine colposcopy.