REVIEW Endometrial carcinoma in high-risk populations: is it time to consider a screening policy? M. Fambrini, F. Sorbi, G. Sisti, R. Cioni, I. Turrini, G. Taddei and S. Guaschino Department of Biomedical, Clinical and Experimental Sciences, University of Florence, Florence, Italy Accepted for publication 28 November 2013 M. Fambrini, F. Sorbi, G. Sisti, R. Cioni, I. Turrini, G. Taddei and S. Guaschino Endometrial carcinoma in high-risk populations: is it time to consider a screening policy? Endometrial carcinoma (EC) is the leading female genital tract malignancy in industrialized countries. It will become an important public health problem in the coming years in the USA and Europe, where its incidence is increasing, and next-generation interventions should include periodical screening in high-risk women. In this review, we discuss the importance to gynaecologists of detecting women at high risk and offering an adequate screening programme. Screening for EC is particularly challenging and there is currently no proven programme for the surveillance of women estimated to be at an increased risk of developing this form of can- cer. The data in the literature, including this and previous issues of Cytopathology, and personal experience sug- gest that endometrial liquid-based cytology (LBC) might play an essential role in a screening policy for EC. LBC may enable practitioners to reduce age-adjusted mortality for women at high risk for EC. Keywords: endometrial carcinoma, cancer screening, liquid-based cytology Introduction Endometrial carcinoma (EC) is the commonest malignancy of the female genital tract in the USA and Europe, accounting for nearly 50% of all new diagnoses of gynaecological cancer. 1–3 The incidence of EC increased from 13.5 to 20.3 per 100 000 between 1993 and 2010 in the UK, 4 and the inci- dence and mortality have been reported to have increased by 1.1% and 0.3%, respectively, annually during the same period of time in the USA. 5 The incidence of EC is also increasing in Japan, even in younger age groups, 6 where it has become more fre- quent each year over a period of 30 years, and as a proportion of all uterine carcinoma rose from 10% in 1983 to 45% in 2004. 7 The main risk factors for EC are obesity, diabetes, oestrogen use, tamoxifen treat- ment, polycystic ovarian syndrome (PCOS), a history of infertility, alcohol abuse and antidepressant agents. 8–11 Many of these factors are tightly linked to current lifestyles in developed countries. A small but significant percentage (about 2–3%) of EC is attribut- able to Lynch syndrome, a hereditary cancer predis- position syndrome which significantly increases the risk of colorectal, endometrial and other cancers. 1,2 Traditionally, EC has been considered to have a favourable prognosis with high curability as it is usu- ally confined to the uterus at the time of diagnosis. 1,2,12 However, even though the incidence of EC has risen only slightly over the past two decades, the number of estimated deaths per year from this disease has more than doubled since the 1980s. In this respect, recent findings suggest that the increase in mortality over the last 14 years may be related to an increased rate of advanced-stage cancers, higher tumour grade and non- endometrioid histology. 13 On the basis of these recent reports, it would seem that EC is becoming an increas- ingly important challenge in developed countries. For these reasons, scientists, doctors and public health pro- fessionals are becoming ever more concerned with identifying effective preventative measures for this con- dition, which has a readily available treatment with a potential for cure that increases with early detection. In this article, we review the published literature in order to understand whether a screening policy using liquid-based cytology (LBC) could be consid- ered in selected high-risk groups of patients in devel- oped countries. Correspondence: Prof. M. Fambrini, Department of Biomedical, Clinical and Experimental Sciences, University of Florence, Viale Morgagni, 85, 50134 Florence, Italy Tel: +39 055 7947550; Fax: +39 055 430056; E-mail: maxfambrini@libero.it DOI:10.1111/cyt.12131 71 © 2014 John Wiley & Sons Ltd Cytopathology 2014, 25, 71–77