Evidence of Benefit
Measuring endometrial thickness (ET) with transvaginal ultrasound (TVU) and endometrial sampling with cytological examination have been proposed as possible screening modalities for endometrial cancer. The Papanicolaou (Pap) test, used successfully for screening for cervical cancer, is too insensitive to be used as a screening technique for the detection of endometrial cancer, although occasionally the Pap test may fortuitously identify endometrial abnormalities, such as endometrial cancer.
Routine screening of asymptomatic women for endometrial cancer has not been evaluated for its impact on endometrial cancer mortality.[2,3] Although high-risk groups can be identified, the benefit of screening in reducing endometrial cancer mortality in these high-risk groups has not been evaluated. Using the same cutoffs to define an abnormal ET in asymptomatic women  as used in symptomatic women  would result in large numbers of false-positive test results and larger numbers of unnecessary referrals for cytological evaluations. Published recommendations for screening certain groups of women at high risk for endometrial carcinoma are based on opinion regarding presumptive benefit.
Modalities of Endometrial Cancer Screening
Ultrasonography in women with vaginal bleeding
TVU is used as a diagnostic tool to evaluate symptomatic women with vaginal bleeding. Among women with postmenopausal uterine bleeding and cancer, 96% will have an abnormal ET (>6 mm). The specificity varies by whether women used hormone therapy. Among nonusers, the specificity was 92%. Much less work has been done to evaluate the accuracy of TVU among asymptomatic women. If the same endometrial thickness cutoff is used among asymptomatic women, the false positives will be extremely high, resulting in a very low positive predictive value. No studies have evaluated the efficacy of screening with TVU in reducing mortality from endometrial cancer.
A group of researchers used dilation and curettage (D&C) as a gold standard, to evaluate TVU measurement of ET as a predictor of endometrial cancer in women reporting postmenopausal bleeding (estrogen-progestin therapy [hormone therapy] and nonhormone therapy users). Of the 339 participants, 39 (11.5%) were diagnosed with endometrial cancer (four had an ET of 5–7 mm and 35 had an ET > 8 mm) based on histopathology from curettage. No cancers were detected in women with an ET of less than 4 mm. Using a cutoff point of 4 mm, TVU has 100% sensitivity and 60% specificity. In this population, 46% (156) of the women had an ET greater than 4 mm.
Ultrasonography in women without vaginal bleeding
A comparison of TVU and endometrial aspiration was conducted among asymptomatic postmenopausal women potentially eligible for an osteoporosis prevention trial  as part of determination of eligibility for randomization. TVU was performed on 1,926 women. Of these, 93 women had ET greater than 6 mm. Among the 93 women with abnormal ET, 42 had endometrial aspiration with one finding of abnormal pathology (defined as adenocarcinoma or atypical hyperplasia). Of the 1,833 women with ET measuring 6 mm or less, 1,750 women had endometrial aspiration and five of these women had an abnormal pathologic biopsy. Among this population of asymptomatic postmenopausal women, the estimated sensitivity for TVU with a threshold value of 6 mm was 17% and 33% for a threshold value of 5 mm.
One study assessed the usefulness of TVU among a cohort of postmenopausal, asymptomatic women receiving hormone therapy. Utilizing the Postmenopausal Estrogen and Progestin Interventions Trial participants who had undergone both TVU and endometrial biopsy, sensitivity, specificity, positive predictive value, and negative predictive value were determined for women who received placebo, estrogen alone, and estrogen-progestin therapy. At a threshold value of 5 mm for ET, TVU had 90% sensitivity and 48% specificity. Using this threshold, more than half the women would receive a biopsy while only 4% of them had serious disease.
Another study obtained endometrial biopsy specimens from 801 asymptomatic perimenopausal and postmenopausal women prior to enrollment in a hormone therapy study. Of the specimens, 75% of the samples contained sufficient tissue for diagnosis. Among these women, one case of endometrial cancer was diagnosed, illustrating the low yield of screening among asymptomatic women and the difficulty with endometrial cavity access.
Although TVU can be used to evaluate asymptomatic and occult endometrial pathology, the technique has not been evaluated as a screening method for reducing mortality in asymptomatic women.
Ultrasonography in women using tamoxifen
Tamoxifen is widely used as part of adjuvant therapy for breast cancer and as chemoprevention for women at increased risk of breast cancer. In addition to the protective effects for breast cancer, the biological and endocrine effects of tamoxifen increase patients’ risk of developing endometrial pathology, including endometrial polyps, endometrial hyperplasia, and endometrial carcinoma.
There is interest in trying to reduce the morbidity from endometrial cancer through early detection, and there has been interest in using endovaginal ultrasound as a method to screen women to detect endometrial cancer.
In a prospective, observational study of 304 women using tamoxifen over 6 years, women underwent annual endovaginal ultrasound screening; women with abnormal ultrasound findings and women who were symptomatic with bleeding all underwent endometrial biopsy. Thirty-two percent of the ultrasound examinations had associated significant uterine abnormalities identified that required further medical or surgical investigation and treatment. However, most abnormalities (80%) represented benign polyps for which no treatment was needed. Six cases of primary endometrial cancer were detected, and all cases presented with irregular bleeding. The sensitivity of ultrasound was only 63.3%, with a specificity of 60.4%, and had a low positive predictive value for cancer of only 1%.
Other reports have noted similar results. Routine ultrasound surveillance in asymptomatic women using tamoxifen is not useful because of its low specificity and low positive predictive value. Evaluation of the endometrium in women taking tamoxifen should be limited to women symptomatic with vaginal bleeding.
Sonohysterography (hydrosonography) is a diagnostic test among asymptomatic women, and is able to separate space occupying endometrial lesions from an abnormal endometrial-myometrial junction in order to help guide biopsies. There is no evidence that routine screening sonohysterography will confer clinical benefit.
Endometrial sampling in women with uterine bleeding
In the setting of abnormal uterine bleeding, endometrial sampling has gained favor largely as an alternative to more invasive procedures such as fractional D&C. Several methods of biopsy exist (e.g., Pipelle, Tao Brush, and Uterine Explora Curette) to identify endometrial pathology. Although endometrial sampling has largely replaced D&C as the first choice in the evaluation of women with bleeding, issues of access to the endometrial cavity and sampling error limit the clinical significance of a negative result. In the Arimidex, Tamoxifen, Alone or in Combination trial, 36% of biopsies had insufficient tissue for diagnosis.
No studies have evaluated the use of endometrial sampling as routine screening in reducing endometrial cancer mortality.
Hysteroscopy is used in the office setting to directly visualize the uterine cavity. A group of researchers noted that hysteroscopy is not as useful in detecting endometrial cancer as biopsy or D&C. It has not been evaluated as a screening tool.
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