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

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Ovarian Cancer Screening

Summary of Evidence

Note: Separate PDQ summaries on Ovarian Cancer Prevention; Ovarian Epithelial Cancer Treatment; Ovarian Germ Cell Tumor Treatment; and Ovarian Low Malignant Potential Tumor Treatment are also available.

CA 125 Levels, Transvaginal Ultrasound, and Pelvic Examinations

Statement of benefit

There is solid evidence to indicate that routine screening for ovarian cancer with the serum marker cancer antigen (CA )125 and transvaginal ultrasound (TVU) does not result in a decrease in mortality from ovarian cancer.

Description of the Evidence

  • Study Design: Evidence obtained from a randomized controlled trial.
  • Internal Validity: Good.
  • Consistency: One trial has evaluated the impact on mortality from ovarian cancer.
  • Magnitude of Effects on Health Outcomes: No reduction in mortality.
  • External Validity: Not applicable (N/A).

Statement of harms

Based on solid evidence, routine screening for ovarian cancer results in many diagnostic laparoscopies and laparotomies for each ovarian cancer found.

Description of the Evidence

  • Study Design: Evidence obtained from cohort studies and randomized trials.
  • Internal Validity: Good.
  • Consistency: Volume of evidence is limited but consistent and coherent.
  • Magnitude of Effects on Health Outcomes: The number of surgeries performed per invasive cancer diagnosed with combination screening using CA 125 measures and transvaginal ultrasound is about 20.
  • External Validity: Good.

Significance

Incidence and Mortality

Ovarian cancer is the fifth leading cause of cancer death among women in the United States and has the highest mortality rate of all gynecologic cancers.[1] It is estimated that 22,280 new cases of ovarian cancer will be diagnosed in the United States in 2012, and 15,500 women will die of this disease.[1] The median age at diagnosis is 63 years.[2] The prognosis for survival from ovarian cancer largely depends on the extent of disease at diagnosis. The overall 5-year survival rate for ovarian cancer is lower than 50%. Fewer than one-fourth of women present with localized disease at diagnosis.[1,3]

Incidence has been relatively stable since 1992, and mortality rates decreased by 1.9% per year from 2004 to 2008.[1]

Ovarian cancer is rare; the lifetime risk of being diagnosed with ovarian cancer is 1.39%.[3]

Factors Associated With Ovarian Cancer

Several hypotheses have proposed the underlying mechanisms leading to ovarian cancer. Proposed mechanisms include incessant ovulation, hormonal factors such as androgen or gonadotropins, or inflammation.[4] Risk factors support several of these hypotheses, suggesting several possible pathways to ovarian cancer.

Multiparity, oral contraceptive use, and breastfeeding are associated with a decreased risk of ovarian cancer.[5] Oophorectomy reduces but does not eliminate the risk of ovarian cancer because primary peritoneal carcinomatosis may occur.[6,7,8] A history of tubal ligation or hysterectomy with ovarian conservation is also associated with a decreased risk of ovarian cancer.[9]

Risk is increased in women with a family history of ovarian cancer,[5,10,11] with the postmenopausal use of hormone therapy,[12,13] and among women who have used fertility drugs.[5,14] Obesity, tall height, and high body mass index have also been associated with increased risk of ovarian cancer.[15,16,17]

Age at menarche, age at menopause, or age at first live birth is unrelated to the risk of ovarian cancer.[5] Other factors such as perineal exposure to talcum powder have been investigated as possible risk factors for ovarian cancer, but results are conflicting.[18,19]

Several inherited cancer syndromes are associated with an increased risk of ovarian cancer. Families with a history of both ovarian cancer and early-onset breast cancer are suggestive of inherited BRCA1 or BRCA2 gene mutations. (Refer to the PDQ summary on Genetics of Breast and Ovarian Cancer for more information.) An increased risk of ovarian cancer is also associated with hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome. (Refer to the PDQ summary on Genetics of Colorectal Cancer for more information.) Ovarian-only inherited cancer syndromes have also been described, but the gene or genes involved have not yet been identified. Individuals with an inherited risk for ovarian cancer form a special risk group. (Refer to the PDQ summaries on Cancer Genetics Overview; Genetics of Medullary Thyroid Cancer; and Genetics of Prostate Cancer for more information.)

References:

1. American Cancer Society.: Cancer Facts and Figures 2012. Atlanta, Ga: American Cancer Society, 2012. Available online. Last accessed June 14, 2012.
2. Ries LAG, Harkins D, Krapcho M, et al.: SEER Cancer Statistics Review, 1975-2003. Bethesda, Md: National Cancer Institute, 2006. Also available online. Last accessed September 1, 2011.
3. Altekruse SF, Kosary CL, Krapcho M, et al.: SEER Cancer Statistics Review, 1975-2007. Bethesda, Md: National Cancer Institute, 2010. Also available online. Last accessed June 1, 2012.
4. Ness RB, Cottreau C: Possible role of ovarian epithelial inflammation in ovarian cancer. J Natl Cancer Inst 91 (17): 1459-67, 1999.
5. Whittemore AS, Harris R, Itnyre J: Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group. Am J Epidemiol 136 (10): 1184-203, 1992.
6. Schmeler KM, Lynch HT, Chen LM, et al.: Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 354 (3): 261-9, 2006.
7. Rebbeck TR, Lynch HT, Neuhausen SL, et al.: Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346 (21): 1616-22, 2002.
8. Offit K, Kauff ND: Reducing the risk of gynecologic cancer in the Lynch syndrome. N Engl J Med 354 (3): 293-5, 2006.
9. Hankinson SE, Hunter DJ, Colditz GA, et al.: Tubal ligation, hysterectomy, and risk of ovarian cancer. A prospective study. JAMA 270 (23): 2813-8, 1993.
10. Cramer DW, Hutchison GB, Welch WR, et al.: Determinants of ovarian cancer risk. I. Reproductive experiences and family history. J Natl Cancer Inst 71 (4): 711-6, 1983.
11. Stratton JF, Pharoah P, Smith SK, et al.: A systematic review and meta-analysis of family history and risk of ovarian cancer. Br J Obstet Gynaecol 105 (5): 493-9, 1998.
12. Garg PP, Kerlikowske K, Subak L, et al.: Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis. Obstet Gynecol 92 (3): 472-9, 1998.
13. Anderson GL, Judd HL, Kaunitz AM, et al.: Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. JAMA 290 (13): 1739-48, 2003.
14. Koch M, Gaedke H, Jenkins H: Family history of ovarian cancer patients: a case-control study. Int J Epidemiol 18 (4): 782-5, 1989.
15. Calle EE, Rodriguez C, Walker-Thurmond K, et al.: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348 (17): 1625-38, 2003.
16. Schouten LJ, Goldbohm RA, van den Brandt PA: Height, weight, weight change, and ovarian cancer risk in the Netherlands cohort study on diet and cancer. Am J Epidemiol 157 (5): 424-33, 2003.
17. Engeland A, Tretli S, Bjørge T: Height, body mass index, and ovarian cancer: a follow-up of 1.1 million Norwegian women. J Natl Cancer Inst 95 (16): 1244-8, 2003.
18. Cramer DW, Liberman RF, Titus-Ernstoff L, et al.: Genital talc exposure and risk of ovarian cancer. Int J Cancer 81 (3): 351-6, 1999.
19. Wong C, Hempling RE, Piver MS, et al.: Perineal talc exposure and subsequent epithelial ovarian cancer: a case-control study. Obstet Gynecol 93 (3): 372-6, 1999.

Evidence of Benefit

Potential screening tests for ovarian cancer include transvaginal ultrasound (TVU) and the serum cancer antigen (CA) 125 assay. Several biomarkers with potential application to ovarian cancer screening are under development but have not yet been validated or evaluated for efficacy in early detection and mortality reduction.

Bimanual pelvic examination is a part of the routine pelvic examination. The sensitivity and specificity of the pelvic examination are not characterized, but examination generally detects advanced disease.[1,2]

The Pap test may occasionally detect malignant ovarian cells, but it is not sensitive (reported sensitivity of 10%–30%) and has not been evaluated for the early detection of ovarian cancer.[1] Another method of detection, cytologic examination of peritoneal lavage obtained by culdocentesis, is technically difficult, is uncomfortable for the patient, has low sensitivity for detecting early-stage disease, and has not been evaluated for screening.[1,3]

Ultrasonography

TVU has been proposed as a screening method for ovarian cancer because of its ability to reliably measure ovarian size and detect small masses.[4] The benefit of ultrasonography for the early detection of ovarian cancer and reduction in mortality has not been evaluated in controlled studies. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) is an ongoing randomized clinical trial evaluating the efficacy of annual TVU in combination with CA 125 tests to reduce ovarian cancer mortality.

An estimate of the false-positive rate associated with screening women aged 55 to 74 years is available from the initial four rounds of screening of women who participated in the PLCO and who were randomly assigned to be screened with TVU and serum CA 125 concentrations.[5,6] Among the 39,115 women randomly assigned to the screening arm, 34,261 were eligible for screens because they had not had a prior oophorectomy. Among these women, 89% had at least one screen during the four rounds of screening. The following TVU results were classified as abnormal (positive): "ovarian volume greater than 10 cm3; cyst volume greater than 10 cm3; any solid area or papillary projection extending into the cavity of a cystic ovarian tumor of any size; or any mixed (solid/cystic) component within a cystic ovarian tumor."[5,6] The screen positivity rates decreased slightly from 4.6% at the prevalent (baseline screen) to 2.9% at the fourth round of screening. The positive predictive value (PPV) of TVU was relatively constant over the screening rounds ranging from 0.7% to 1.1%.

Accurate estimates of sensitivity and specificity are difficult to obtain because few studies have conducted adequate follow-up to identify all cases. The U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) published results from their prevalent screen. The ultrasound screening arm had several levels of screening and possible referral strategies: an abnormal scan resulted in a repeat scan in 6 to 8 weeks, and if still abnormal, referral was made for a clinical assessment. Of 53 total cancers (screen-detected and interval cancers in the following year), 45 were screened positive by ultrasound (two abnormal scans) for a sensitivity of 84.9%. For invasive cancer, the sensitivity was 75%. Specificity of the ultrasound screening arm was calculated at 98.2%.[7]

CA 125 Levels

CA 125 is a tumor-associated antigen that is used clinically to monitor patients with epithelial ovarian carcinomas.[8,9] The measurement of CA 125 levels, in combination with TVU,[10] is the ovarian screening intervention being evaluated in the PLCO.[5,11] The most commonly reported CA 125 reference value that designates a positive screening test is 35 U/mL, and this was the reference value used in the PLCO to define an abnormal test result. Elevated CA 125 levels are not specific to ovarian cancer and have been observed in patients with nongynecological cancers [9] and in the presence of other conditions such as the first trimester of pregnancy [12,13] or endometriosis.[14] The sensitivity of the CA 125 test for the detection of ovarian cancer was estimated in two nested case-control studies using serum banks.[15,16] The sensitivity for CA 125 levels of at least 35 U/mL ranged from 20% to 57% for cases occurring within the first 3 years of follow-up; the specificity was 95%. The positive rates across the first four rounds of screening in the PLCO trial were fairly constant, ranging from 1.4% to 1.7% and were lower than the rates for TVU. The PPV was higher for CA 125 than for TVU, ranging from 2.1% to 3.2% in the four rounds of screening.

Another study, the Shizuoka Cohort Study of Ovarian Cancer Screening randomly assigned women to a screening group (n = 41,668) or a control group (n = 40,799) between 1985 and 1999 at 212 hospitals in the Shizuoka prefecture of Japan. The screening protocol comprised ultrasound and CA 125 tests annually. Women with abnormal findings were referred to a gynecological oncologist. Ovarian cancer diagnoses were determined by record linkage to the Shizuoka Cancer Registry in 2002. The annual death certificate file in Shizuoka was checked to ascertain vital status. The mean follow-up time was 9.2 years, and the mean number of screens per woman was 5.4. There were 35 ovarian cancers detected in the screening group and 32 in the control group with a nonsignificant difference in the stage distribution. Nine percent of regular screening attendees had at least one false-positive result.[17]

A CA 125 screening program of 22,000 postmenopausal women with subsequent transabdominal ultrasound for those with elevated CA 125 levels (reference value of 30 U/mL) detected 11 of 19 cases of ovarian cancer occurring in the cohort, for an apparent sensitivity of 58%.[18] The specificity for this screening study was 99.9%. Three of the 11 cases detected through screening were stage I disease. In one prospective screening study, the specificity of CA 125 levels of 35 U/mL was 97.6%.[19] Ten-year follow-up of this cohort of 5,550 women screened from 1987 to 1989 in the Stockholm region of Sweden revealed 29 ovarian cancers versus 24 expected cases. Compared with the cancers diagnosed after the screening period, those detected by CA 125 tests had a higher proportion of early-stage disease and better survival measured from diagnosis. Both end points, however, are subject to bias, and the survival of all ovarian cancers combined did not differ from the age-adjusted ovarian cancer survival in the Stockholm population.[20]

A pilot randomized trial in the United Kingdom randomly assigned 10,977 women to a control group and 10,958 women to a screened group in 1989.[21] The primary screen was the CA 125 test, followed by ultrasonography when CA 125 levels were elevated. Women were offered three annual screening rounds, and both groups were followed for 7 years. Compliance was 70.7% for all three screenings and 85.5% for at least one screening. There were 20 ovarian cancers in the control group and 16 in the screened group, only six of which were detected by screening. There was a higher proportion of stage I/II cancers in the screened group (31.3% vs. 10.0%). There were 18 ovarian cancer deaths in the control group and nine in the screened group (relative risk = 2.0; 95% confidence interval [CI], 0.78–5.13). The outcome for women with ovarian cancer in the control group, however, was unexpectedly poor.

Women with mutations in genes associated with breast and ovarian cancer family syndromes or hereditary nonpolyposis colorectal cancer are at an increased risk for the development of ovarian cancer. No controlled studies have evaluated the efficacy of ovarian cancer screening in this population. A Dutch study of BRCA1- or BRCA2-mutation carriers involved surveillance via annual TVUs and serum CA 125 measurements beginning in women aged 30 to 35 years. Six cases of ovarian cancer were detected, all of which were in the advanced stage of disease.[22,23]

Combined Screening With CA 125 and TVU

The objective of the ovarian component of the PLCO trial was to evaluate the effect of screening on ovarian cancer mortality. The trial included 78,216 women aged 55 to 74 years who were randomly assigned to undergo either annual screening (n = 39,105) or usual care (n = 39,111) at ten screening centers across the United States between November 1993 and July 2001. The intervention group was offered annual screening with CA 125 for 6 years and TVU for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered screening with CA 125 or TVU but received their usual medical care. Participants were followed for a maximum of 13 years (median, 12.4 years; range, 10.9–13.0 years) for cancer diagnoses and death until February 28, 2010. Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers, was the main outcome measure. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures.[24]

Compliance with screening ranged from 85% at the initial round to 73% at the sixth round, while contamination in the usual care group ranged from about 3.0% for CA 125 to 4.6% for TVU. Across the first four screening rounds, 11.1% of women had at least one positive test, 8.1% had at least one positive TVU, and 3.4% had at least one positive CA 125 test. The yields of both tests were similar. Ovarian cancer was diagnosed in 212 women (5.7 per 10,000 person-years) in the intervention group and 176 women (4.7 per 10,000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% CI, 0.99–1.48). The stage distributions were similar by study group with stage III and IV cancers comprising the majority of cases in both the intervention group (163 cases, 77%) and the usual care group (137 cases, 78%). The cancer case treatment distributions were very similar between groups within each stage. There were 118 deaths caused by ovarian cancer (3.1 per 10,000 person-years) in the intervention group and 100 deaths (2.6 per 10,000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82–1.71). Of the 3,285 women with false-positive results, 1,080 underwent surgical follow-up; of whom, 163 women experienced at least one serious complication (15%). A total of 1,771 women in the intervention group (7.7%) and 1,304 in the usual care group (5.8%) reported oophorectomy. There were 2,924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10,000 person-years) in the intervention group and 2,914 such deaths (76.2 per 10,000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96–1.06).[6,24]

Among women in the general U.S. population, simultaneous screening with CA 125 and TVU compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications.

In the UKCTOCS trial,[7] multimodality screening included a two-stage screening arm with CA 125 measured and used to estimate an ovarian cancer risk score. That risk score determined follow-up. Elevated risk was followed with a transvaginal ultrasound. Intermediate risk scores were followed up with a repeat CA 125 measure and recalculation of the risk score, if risk remained intermediate or higher than an ultrasound. The reported sensitivity and specificity scores from the prevalent screen for the multimodality screening arm were 89.4% and 99.8% overall; 89.5% and 99.8% for invasive cancers.

Other Markers

Proteomics has been used to identify patterns or specific serum markers that may be used in place of, or in conjunction with, CA 125 measurements for the early detection of cancer.[25,26] These studies have been small case-control studies that are limited by sample size and by the number of early-stage cancer cases included. Further evaluation is needed to determine whether any additional markers have clinical utility for the early detection of ovarian cancer.

References:

1. Smith LH, Oi RH: Detection of malignant ovarian neoplasms: a review of the literature. I. Detection of the patient at risk; clinical, radiological and cytological detection. Obstet Gynecol Surv 39 (6): 313-28, 1984.
2. Hall DJ, Hurt WG: The adnexal mass. J Fam Pract 14 (1): 135-40, 1982.
3. Keettel WC, Pixley EE, Buchsbaum HJ: Experience with peritoneal cytology in the management of gynecologic malignancies. Am J Obstet Gynecol 120 (2): 174-82, 1974.
4. Higgins RV, van Nagell JR Jr, Woods CH, et al.: Interobserver variation in ovarian measurements using transvaginal sonography. Gynecol Oncol 39 (1): 69-71, 1990.
5. Buys SS, Partridge E, Greene MH, et al.: Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial: findings from the initial screen of a randomized trial. Am J Obstet Gynecol 193 (5): 1630-9, 2005.
6. Partridge E, Kreimer AR, Greenlee RT, et al.: Results from four rounds of ovarian cancer screening in a randomized trial. Obstet Gynecol 113 (4): 775-82, 2009.
7. Menon U, Gentry-Maharaj A, Hallett R, et al.: Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 10 (4): 327-40, 2009.
8. Bast RC Jr, Feeney M, Lazarus H, et al.: Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest 68 (5): 1331-7, 1981.
9. Bast RC Jr, Klug TL, St John E, et al.: A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med 309 (15): 883-7, 1983.
10. Jacobs I, Stabile I, Bridges J, et al.: Multimodal approach to screening for ovarian cancer. Lancet 1 (8580): 268-71, 1988.
11. Gohagan JK, Levin DL, Prorok JC, et al., eds.: The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial. Control Clin Trials 21(6 suppl): 249S-406S, 2000.
12. Niloff JM, Knapp RC, Schaetzl E, et al.: CA125 antigen levels in obstetric and gynecologic patients. Obstet Gynecol 64 (5): 703-7, 1984.
13. Haga Y, Sakamoto K, Egami H, et al.: Evaluation of serum CA125 values in healthy individuals and pregnant women. Am J Med Sci 292 (1): 25-9, 1986.
14. Jacobs I, Bast RC Jr: The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod 4 (1): 1-12, 1989.
15. Zurawski VR Jr, Orjaseter H, Andersen A, et al.: Elevated serum CA 125 levels prior to diagnosis of ovarian neoplasia: relevance for early detection of ovarian cancer. Int J Cancer 42 (5): 677-80, 1988.
16. Helzlsouer KJ, Bush TL, Alberg AJ, et al.: Prospective study of serum CA-125 levels as markers of ovarian cancer. JAMA 269 (9): 1123-6, 1993.
17. Kobayashi H, Yamada Y, Sado T, et al.: A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer 18 (3): 414-20, 2008 May-Jun.
18. Jacobs I, Davies AP, Bridges J, et al.: Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography. BMJ 306 (6884): 1030-4, 1993.
19. Einhorn N, Sjövall K, Knapp RC, et al.: Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer. Obstet Gynecol 80 (1): 14-8, 1992.
20. Einhorn N, Bast R, Knapp R, et al.: Long-term follow-up of the Stockholm screening study on ovarian cancer. Gynecol Oncol 79 (3): 466-70, 2000.
21. Jacobs IJ, Skates SJ, MacDonald N, et al.: Screening for ovarian cancer: a pilot randomised controlled trial. Lancet 353 (9160): 1207-10, 1999.
22. Vasen HF, Tesfay E, Boonstra H, et al.: Early detection of breast and ovarian cancer in families with BRCA mutations. Eur J Cancer 41 (4): 549-54, 2005.
23. Olivier RI, Lubsen-Brandsma MA, Verhoef S, et al.: CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer. Gynecol Oncol 100 (1): 20-6, 2006.
24. Buys SS, Partridge E, Black A, et al.: Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 305 (22): 2295-303, 2011.
25. Zhang Z, Bast RC Jr, Yu Y, et al.: Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer. Cancer Res 64 (16): 5882-90, 2004.
26. Petricoin EF, Ardekani AM, Hitt BA, et al.: Use of proteomic patterns in serum to identify ovarian cancer. Lancet 359 (9306): 572-7, 2002.

Changes to This Summary (01 / 26 / 2012)

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.

Significance

Updated statistics with estimated new cases and deaths for 2012 (cited American Cancer Society as reference 1).

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About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about ovarian cancer screening. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

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Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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National Cancer Institute: PDQ® Ovarian Cancer Screening. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/screening/ovarian/HealthProfessional. Accessed <MM/DD/YYYY>.

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