Endometrial Cancer Screening (PDQ®): Screening - Health Professional Information [NCI]

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,[11] 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.[22,33] 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 [44] as used in symptomatic women [55] 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 of endometrial carcinoma are based on opinion regarding presumptive benefit.[66]

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%.[55] Much less work has been done to evaluate the accuracy of TVU among asymptomatic women. If the same ET cutoff is used among asymptomatic women, the false positives will be extremely high, resulting in a very low positive predictive value.[44] 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 (PMB) (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.[77] 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 [88] 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 pathological 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.[99]

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.[1010]

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%.[1111]

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

Sonohysterography (hydrosonography) is a diagnostic test used to help guide biopsies in asymptomatic women that is able to separate space occupied by endometrial lesions from an abnormal endometrial-myometrial junction. 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. A meta-analysis of PMB reported that 91% (95% confidence interval [CI], 87%–93%) of women with endometrial cancer reported PMB. However, among women with PMB, only 9% (95% CI, 8%–11%) were diagnosed with endometrial cancer. This report is limited by a lack of histology-specific estimates.[1212,1313]

No studies have evaluated the use of endometrial sampling as routine screening in reducing endometrial cancer mortality.

Hysteroscopy

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.[1414] It has not been evaluated as a screening tool.[1515]

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.
2. Pritchard KI: Screening for endometrial cancer: is it effective? Ann Intern Med 110 (3): 177-9, 1989.
3. Eddy D: ACS report on the cancer-related health checkup. CA Cancer J Clin 30 (4): 193-240, 1980 Jul-Aug.
4. Smith-Bindman R, Weiss E, Feldstein V: How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynecol 24 (5): 558-65, 2004.
5. 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.
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.
7. 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.
8. 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.
9. 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.
10. Archer DF, McIntyre-Seltman K, Wilborn WW, et al.: Endometrial morphology in asymptomatic postmenopausal women. Am J Obstet Gynecol 165 (2): 317-20; discussion 320-2, 1991.
11. Fung MF, Reid A, Faught W, et al.: Prospective longitudinal study of ultrasound screening for endometrial abnormalities in women with breast cancer receiving tamoxifen. Gynecol Oncol 91 (1): 154-9, 2003.
12. Clarke MA, Long BJ, Del Mar Morillo A, et al.: Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women: A Systematic Review and Meta-analysis. JAMA Intern Med 178 (9): 1210-1222, 2018.
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.
14. Bradley WH, Boente MP, Brooker D, et al.: Hysteroscopy and cytology in endometrial cancer. Obstet Gynecol 104 (5 Pt 1): 1030-3, 2004.
15. Gumus II, Keskin EA, Kiliç E, et al.: Diagnostic value of hysteroscopy and hysterosonography in endometrial abnormalities in asymptomatic postmenopausal women. Arch Gynecol Obstet 278 (3): 241-4, 2008.

Special Populations

Hormone Therapy

There is no evidence to suggest that screening women prior to or during estrogen-progestin therapy, also known as hormone therapy, would decrease endometrial cancer mortality.[11,22] Thus, women on hormone therapy should have a prompt diagnostic work-up for abnormal bleeding. Although women using certain hormone regimens have an increased risk of endometrial cancer, most women who develop cancer will have vaginal bleeding. There is no evidence that screening these women would decrease mortality from endometrial cancer.

Hereditary Nonpolyposis Colorectal Cancer

The lifetime risk of endometrial cancer for women with hereditary nonpolyposis colorectal cancer (HNPCC) and for women who are at high risk for HNPCC is as high as 60%. These cases are often diagnosed in the fifth decade, 10 to 20 years earlier than sporadic cases.[33,44,55,66,77] Based on limited evidence, it appears that 5-year survival among women with HNPCC diagnosed with endometrial cancer is similar to that of nonhereditary cases in the general population.[88] Because the risk of endometrial cancer is so high among these women, international guidelines suggest gynecologic surveillance including annual transvaginal ultrasound with endometrial biopsy for women aged 25 to 35 years.[99,1010] The most recent American Cancer Society Cancer Detection Guidelines (updated January 2005) recommend annual screening with endometrial biopsy beginning at age 35 years.[1111]

Women Treated With Tamoxifen

The risk of endometrial cancer is increased in women who are treated with tamoxifen and is even greater in the subset of women who have a history of prior estrogen therapy.[1212] Beyond a routine gynecologic examination eliciting any history of abnormal bleeding, it has been recommended that screening studies and procedures for detecting endometrial pathology in women taking tamoxifen should be left to the discretion of the individual gynecologist.[1313] Commonly, there are endometrial abnormalities in women taking tamoxifen, especially in false-positive endovaginal ultrasound screening tests. More importantly, any abnormal uterine bleeding should be completely evaluated.

Endometrial cancers that occur in tamoxifen-treated women are very similar to those cancers occurring in the general population, with respect to stage, grade, and histology.[1414,1515,1616] Prognosis is good and not affected by early detection.[1717]

There have been no published studies evaluating the effect of endometrial cancer-screening modalities on mortality among women taking tamoxifen for breast cancer treatment or prevention.

References:

1. ACOG committee opinion. Routine cancer screening. Number 185, September 1997 (replaces no. 128, October 1993). Committee on Gynecologic Practice. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 59 (2): 157-61, 1997.
2. Korhonen MO, Symons JP, Hyde BM, et al.: Histologic classification and pathologic findings for endometrial biopsy specimens obtained from 2964 perimenopausal and postmenopausal women undergoing screening for continuous hormones as replacement therapy (CHART 2 Study). Am J Obstet Gynecol 176 (2): 377-80, 1997.
3. Watson P, Vasen HF, Mecklin JP, et al.: The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer. Am J Med 96 (6): 516-20, 1994.
4. Aarnio M, Sankila R, Pukkala E, et al.: Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81 (2): 214-8, 1999.
5. Vasen HF, Wijnen JT, Menko FH, et al.: Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 110 (4): 1020-7, 1996.
6. Dunlop MG, Farrington SM, Carothers AD, et al.: Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet 6 (1): 105-10, 1997.
7. Lancaster JM, Powell CB, Kauff ND, et al.: Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol 107 (2): 159-62, 2007.
8. Boks DE, Trujillo AP, Voogd AC, et al.: Survival analysis of endometrial carcinoma associated with hereditary nonpolyposis colorectal cancer. Int J Cancer 102 (2): 198-200, 2002.
9. 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.
10. Vasen HF, Mecklin JP, Khan PM, et al.: The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 34 (5): 424-5, 1991.
11. Smith RA, Cokkinides V, Eyre HJ: American Cancer Society Guidelines for the Early Detection of Cancer, 2005. CA Cancer J Clin 55 (1): 31-44; quiz 55-6, 2005 Jan-Feb.
12. Barakat RR: Tamoxifen and endometrial neoplasia. Clin Obstet Gynecol 39 (3): 629-40, 1996.
13. ACOG committee opinion. Tamoxifen and endometrial cancer. Number 169, February 1996. Committee on Gynecologic Practice. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 53 (2): 197-9, 1996.
14. Fisher B, Costantino JP, Wickerham DL, et al.: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90 (18): 1371-88, 1998.
15. Barakat RR, Wong G, Curtin JP, et al.: Tamoxifen use in breast cancer patients who subsequently develop corpus cancer is not associated with a higher incidence of adverse histologic features. Gynecol Oncol 55 (2): 164-8, 1994.
16. Fornander T, Hellström AC, Moberger B: Descriptive clinicopathologic study of 17 patients with endometrial cancer during or after adjuvant tamoxifen in early breast cancer. J Natl Cancer Inst 85 (22): 1850-5, 1993.
17. Barakat RR, Gilewski TA, Almadrones L, et al.: Effect of adjuvant tamoxifen on the endometrium in women with breast cancer: a prospective study using office endometrial biopsy. J Clin Oncol 18 (20): 3459-63, 2000.

Evidence of Harms

Abnormal ultrasound typically requires further investigation including endometrial biopsy (sampling). The evidence is solid that endometrial sampling may result in discomfort, bleeding, infection, and rarely uterine perforation. A study designed to evaluate performance, patient acceptance, and cost-effectiveness of blind biopsy, hysteroscopy with biopsy, and ultrasound, in 683 women with vaginal bleeding, reported that minor events, including discomfort and distress, occurred in 16% of women who had hysteroscopy with biopsy, and in 10% of the women who had a blind biopsy.[11] A group of researchers studied 13,600 diagnostic and operative hysteroscopic procedures and found a lower complication rate among diagnostic procedures (0.13%) compared with operative procedures (0.28%).[22] Risks associated with false-positive test results include anxiety and additional diagnostic testing and surgery. Endometrial cancers may be missed on endometrial sampling and ultrasound.

References:

1. Critchley HO, Warner P, Lee AJ, et al.: Evaluation of abnormal uterine bleeding: comparison of three outpatient procedures within cohorts defined by age and menopausal status. Health Technol Assess 8 (34): iii-iv, 1-139, 2004.
2. Jansen FW, Vredevoogd CB, van Ulzen K, et al.: Complications of hysteroscopy: a prospective, multicenter study. Obstet Gynecol 96 (2): 266-70, 2000.

Latest Updates to This Summary (03 / 15 / 2024)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

SignificanceSignificance

Updated statisticsstatistics with estimated new cases and deaths for 2024 (cited American Cancer Society as reference 1). Also revised text to state that continuing with more recent trends, incidence rates increased by about 1% per year in White women and by 2% to 3% per year in women of all other racial and ethnic groups. Since the mid-2000s, death rates for endometrial cancer increased by 1.7% per year.

This summary is written and maintained by the PDQ Screening and Prevention Editorial BoardPDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ SummaryAbout This PDQ Summary and PDQ® Cancer Information for Health ProfessionalsPDQ® Cancer Information for Health Professionals pages.

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PDQ® Screening and Prevention Editorial Board. PDQ Endometrial Cancer Screening. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/uterine/hp/endometrial-screening-pdqhttps://www.cancer.gov/types/uterine/hp/endometrial-screening-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389229]

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Last Revised: 2024-03-15