Modalities of Endometrial Cancer Screening
        Ultrasonography
        Endometrial sampling

Transvaginal ultrasound (TVU), measuring endometrial thickness (ET), and endometrial sampling with cytological examination have been proposed as possible screening modalities for endometrial cancer. The Pap test, used successfully for screening for cervical cancer, is too insensitive to be used as a screening technique for detection of endometrial cancer.[1] Occasionally, however, the Pap test may fortuitously identify endometrial abnormalities. Sampling the fluid that collects in the posterior vaginal fornix, as part of the Pap test, in perimenopausal and postmenopausal women may occasionally lead to the detection of endometrial lesions. The presence of endometrial cells in a Pap test from a postmenopausal woman, not taking exogenous hormones, is abnormal and requires further evaluation.[2,3]

Routine screening of asymptomatic women for endometrial cancer has not been evaluated for its impact on endometrial cancer mortality.[4,5] Although high-risk groups can be identified, such as women with a uterus taking tamoxifen or using unopposed estrogens and women carrying genetic mutations for hereditary nonpolyposis colorectal cancer, the benefit of screening in reducing endometrial cancer mortality in these high-risk groups has not been evaluated. Published recommendations for screening certain groups of women at high risk for endometrial carcinoma are based on opinion regarding presumptive benefit.[6] Although risk factors include estrogen replacement therapy unopposed by progestins, tamoxifen therapy, and genetic mutations associated with hereditary nonpolyposis colon cancer, no controlled trials have been done to evaluate the effectiveness of screening for endometrial cancer in reducing mortality in these subpopulations.

TVU is used to evaluate symptomatic women with vaginal bleeding. Among women with postmenopausal uterine bleeding and cancer, 96% will have an abnormal endovaginal thickness (>5 mm), however, the specificity at that threshold is only 61%.[7] Much less work has been done to evaluate the accuracy of TVU among asymptomatic women and 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 replacement therapy [HRT/HT] and non-HRT/HT users). Of the 339 participants, 39 (11.5%) were diagnosed with endometrial cancer (four had ET of 5–7 mm, 35 had ET >8 mm) based on histopathology from curettage. No cancers were detected in women with ET less than 4 mm. Using a cutoff point of 4 mm, TVU has 100% sensitivity and 60% specificity.[8] In this population, 46% (156) of the women had ET greater than 4 mm.

A comparison of TVU and endometrial aspiration was conducted among asymptomatic postmenopausal women potentially eligible for an osteoporosis prevention trial [9] 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 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%; 33% for a threshold value of 5 mm.

One study attempted to determine the usefulness of TVU as a less-invasive screening method than biopsy, among a cohort of postmenopausal, asymptomatic women receiving HRT/HT. 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.[10]

Abnormal results from TVU require additional evaluation. 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.

Although sonohysterography (hydrosonography) is able to separate space occupying endometrial lesions from an abnormal endometrial-myometrial junction, evidence is lacking that routine screening sonohysterography will confer clinical benefit.

Color doppler sonography has been reported to be helpful in distinguishing between benign and malignant endometrial pathology in women presenting with postmenopausal bleeding and thickened endometrium (>5 mm).[11,12] The effectiveness of this technique for screening asymptomatic women for the detection of cancer has not been evaluated.

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; however, issues of access to the endometrial cavity and sampling error, limit the clinical significance of a negative result. For example, in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, 36% of biopsies had insufficient tissue for diagnosis.[13] One study obtained endometrial biopsy specimens from 801 asymptomatic perimenopausal and postmenopausal women prior to enrollment in a HRT/HT 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.[14] Several methods (i.e., Pipelle, Tao Brush, Uterine Explora Curette) of endometrial sampling have been evaluated with regard to their ability to accurately identify abnormal endometrial pathology including endometrial cancer. These studies have been conducted among symptomatic populations and are therefore, difficult to assess with respect to their use in the asymptomatic population as widespread screening tools. Histopathologic reports from D&C or hysterectomy remain the gold standard to which these sampling methods should be compared.

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.[15] It has not been evaluated as a screening tool.

References

1. Burk JR, Lehman HF, Wolf FS: Inadequacy of papanicolaou smears in the detection of endometrial cancer. N Engl J Med 291 (4): 191-2, 1974.  [PUBMED Abstract]
   
   
2. Ng AB, Reagan JW, Hawliczek S, et al.: Significance of endometrial cells in the detection of endometrial carcinoma and its precursors. Acta Cytol 18 (5): 356-61, 1974 Sep-Oct.  [PUBMED Abstract]
   
   
3. Yancey M, Magelssen D, Demaurez A, et al.: Classification of endometrial cells on cervical cytology. Obstet Gynecol 76 (6): 1000-5, 1990.  [PUBMED Abstract]
   
   
4. Pritchard KI: Screening for endometrial cancer: is it effective? Ann Intern Med 110 (3): 177-9, 1989.  [PUBMED Abstract]
   
   
5. Eddy D: ACS report on the cancer-related health checkup. CA Cancer J Clin 30 (4): 193-240, 1980 Jul-Aug.  [PUBMED Abstract]
   
   
6. Burke W, Petersen G, Lynch P, et al.: Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium. JAMA 277 (11): 915-9, 1997.  [PUBMED Abstract]
   
   
7. Smith-Bindman R, Kerlikowske K, Feldstein VA, et al.: Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities. JAMA 280 (17): 1510-7, 1998.  [PUBMED Abstract]
   
   
8. Gull B, Karlsson B, Milsom I, et al.: Can ultrasound replace dilation and curettage? A longitudinal evaluation of postmenopausal bleeding and transvaginal sonographic measurement of the endometrium as predictors of endometrial cancer. Am J Obstet Gynecol 188 (2): 401-8, 2003.  [PUBMED Abstract]
   
   
9. Fleischer AC, Wheeler JE, Lindsay I, et al.: An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms. Am J Obstet Gynecol 184 (2): 70-5, 2001.  [PUBMED Abstract]
   
   
10. Langer RD, Pierce JJ, O'Hanlan KA, et al.: Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. Postmenopausal Estrogen/Progestin Interventions Trial. N Engl J Med 337 (25): 1792-8, 1997.  [PUBMED Abstract]
    
    
11. Epstein E, Skoog L, Isberg PE, et al.: An algorithm including results of gray-scale and power Doppler ultrasound examination to predict endometrial malignancy in women with postmenopausal bleeding. Ultrasound Obstet Gynecol 20 (4): 370-6, 2002.  [PUBMED Abstract]
    
    
12. Alcázar JL, Castillo G, Mínguez JA, et al.: Endometrial blood flow mapping using transvaginal power Doppler sonography in women with postmenopausal bleeding and thickened endometrium. Ultrasound Obstet Gynecol 21 (6): 583-8, 2003.  [PUBMED Abstract]
    
    
13. Duffy S, Jackson TL, Lansdown M, et al.: The ATAC adjuvant breast cancer trial in postmenopausal women: baseline endometrial subprotocol data. BJOG 110 (12): 1099-106, 2003.  [PUBMED Abstract]
    
    
14. Archer DF, McIntyre-Seltman K, Wilborn WW Jr, et al.: Endometrial morphology in asymptomatic postmenopausal women. Am J Obstet Gynecol 165 (2): 317-20; discussion 320-2, 1991.  [PUBMED Abstract]
    
    
15. Bradley WH, Boente MP, Brooker D, et al.: Hysteroscopy and cytology in endometrial cancer. Obstet Gynecol 104 (5 Pt 1): 1030-3, 2004.  [PUBMED Abstract]
    
    

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