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Ovarian Cancer Screening and Early Detection

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Advances in Diagnosis and Management of Ovarian Cancer

Abstract

Ovarian cancer is the most deadly gynecologic malignancy due to the fact that most patients have advanced disease at the time of diagnosis. Early ovarian cancer is not associated with identifiable symptoms and screening efforts have not been able to significantly impact the mortality from this malignancy for multiple reasons. While work has been directed toward developing more sensitive tests, ovarian cancer appears to develop in the fallopian tube and will spread diffusely in the abdominal cavity prior to detection. Single agent biomarker tests and even multimodal tests that incorporate multiple tumor markers and ultrasound have been developed. While these types of tests are relatively sensitive for detecting the presence of ovarian cancer in women when a mass develops, they do not perform well as a screening test in asymptomatic women. While some tests can detect some ovarian cancer at an earlier stage, they are not cost-effective and are not likely to decrease the overall mortality significantly. It is hoped that ovarian cancer precursors can be detected using cytology or by examining molecular signatures to provide early detection and reduction of mortality from ovarian cancer.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.

    PubMed  Google Scholar 

  2. DiSaia PJ, Creasman WT. The adnexal mass and early ovarian cancer. In: Clinical gynecological oncology. Mosby-year book. St. Louis: C.V. Mosby; 1997. p. 253–81.

    Google Scholar 

  3. Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A, Siegel RL. Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018;68:284–96.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Diaz-Padilla I, Malpica AL, Minig L, Chiva LM, Gershenson DM, Gonzalez-Martin A. Ovarian low-grade serous carcinoma: a comprehensive update. Gynecol Oncol. 2012;126:279–85.

    Article  PubMed  Google Scholar 

  5. Kurman RJ, Shih IM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010;34:433–43.

    Article  PubMed  PubMed Central  Google Scholar 

  6. del Carmen MG, Birrer M, Schorge JO. Clear cell carcinoma of the ovary: a review of the literature. Gynecol Oncol. 2012;126:481–90.

    Article  PubMed  Google Scholar 

  7. Samartzis EP, Noske A, Dedes KJ, Fink D, Imesch P. ARID1A mutations and PI3K/AKT pathway alterations in endometriosis and endometriosis-associated ovarian carcinomas. Int J Mol Sci. 2013;14:18824–49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Wendel JRH, Wang X, Hawkins SM. The endometriotic tumor microenvironment in ovarian cancer. Cancers (Basel). 2018;10(8):261.

    Article  CAS  Google Scholar 

  9. Hart WR. Mucinous tumors of the ovary: a review. Int J Gynecol Pathol. 2005;24:4–25.

    PubMed  Google Scholar 

  10. Jacobs IJ, Menon U. Progress and challenges in screening for early detection of ovarian cancer. Mol Cell Proteomics. 2004;3:355–66.

    Article  PubMed  CAS  Google Scholar 

  11. Menon U, Jacobs IJ. Ovarian cancer screening in the general population: current status. Int J Gynecol Cancer. 2001;11(Suppl 1):3–6.

    Article  PubMed  Google Scholar 

  12. Wilson JM, Jungner YG. [Principles and practice of mass screening for disease]. Bol Oficina Sanit Panam. 1968;65:281–393.

    Google Scholar 

  13. Goff BA, Mandel LS, Drescher CW, Urban N, Gough S, Schurman KM, Patras J, Mahony BS, Andersen MR. Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer. 2007;109:221–7.

    Article  PubMed  Google Scholar 

  14. Andersen MR, Goff BA, Lowe KA, Scholler N, Bergan L, Drescher CW, Paley P, Urban N. Use of a symptom index, CA125, and HE4 to predict ovarian cancer. Gynecol Oncol. 2010;116:378–83.

    Article  PubMed  Google Scholar 

  15. Herbst AL. The epidemiology of ovarian carcinoma and the current status of tumor markers to detect disease. Am J Obstet Gynecol. 1994;170:1099–105; discussion 1105–7.

    Article  PubMed  CAS  Google Scholar 

  16. Niloff JM. Ovarian malignancy. Curr Opin Obstet Gynecol. 1991;3:66–72.

    Article  PubMed  CAS  Google Scholar 

  17. Bristow RE, Smith A, Zhang Z, Chan DW, Crutcher G, Fung ET, Munroe DG. Ovarian malignancy risk stratification of the adnexal mass using a multivariate index assay. Gynecol Oncol. 2013;128:252–9.

    Article  PubMed  Google Scholar 

  18. Coleman RL, Herzog TJ, Chan DW, Munroe DG, Pappas TC, Smith A, Zhang Z, Wolf J. Validation of a second-generation multivariate index assay for malignancy risk of adnexal masses. Am J Obstet Gynecol. 2016;215:82.e1–82.e11.

    Article  Google Scholar 

  19. Zurawski VR Jr, Orjaseter H, Andersen A, Jellum E. Elevated serum CA 125 levels prior to diagnosis of ovarian neoplasia: relevance for early detection of ovarian cancer. Int J Cancer. 1988;42:677–80.

    Article  PubMed  Google Scholar 

  20. Bast RC Jr, Klug TL, St John E, Jenison E, Niloff JM, Lazarus H, Berkowitz RS, Leavitt T, Griffiths CT, Parker L, Zurawski VR Jr, Knapp RC. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med. 1983;309:883–7.

    Article  PubMed  Google Scholar 

  21. Skates SJ, Mai P, Horick NK, Piedmonte M, Drescher CW, Isaacs C, Armstrong DK, Buys SS, Rodriguez GC, Horowitz IR, Berchuck A, Daly MB, Domchek S, Cohn DE, Van Le L, Schorge JO, Newland W, Davidson SA, Barnes M, Brewster W, Azodi M, Nerenstone S, Kauff ND, Fabian CJ, Sluss PM, Nayfield SG, Kasten CH, Finkelstein DM, Greene MH, Lu K. Large prospective study of ovarian cancer screening in high-risk women: CA125 cut-point defined by menopausal status. Cancer Prev Res (Phila). 2011;4:1401–8.

    Article  CAS  Google Scholar 

  22. Gocze P, Vahrson H. [Ovarian carcinoma antigen (CA 125) and ovarian cancer (clinical follow-up and prognostic studies)]. Orv Hetil. 1993;134:915–8.

    Google Scholar 

  23. Jacobs I, Bast RC Jr. The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod. 1989;4:1–12.

    Article  PubMed  CAS  Google Scholar 

  24. Kaku T, Ogawa S, Kawano Y, Ohishi Y, Kobayashi H, Hirakawa T, Nakano H. Histological classification of ovarian cancer. Med Electron Microsc. 2003;36:9–17.

    Article  PubMed  Google Scholar 

  25. Molina R, Filella X, Jo J, Agusti C, Ballesta AM. CA 125 in biological fluids. Int J Biol Markers. 1998;13:224–30.

    Article  PubMed  CAS  Google Scholar 

  26. Slotman BJ, Rao BR. Ovarian cancer (review). Etiology, diagnosis, prognosis, surgery, radiotherapy, chemotherapy and endocrine therapy. Anticancer Res. 1988;8:417–34.

    PubMed  CAS  Google Scholar 

  27. Woolas RP, Xu FJ, Jacobs IJ, Yu YH, Daly L, Berchuck A, Soper JT, Clarke-Pearson DL, Oram DH, Bast RC Jr. Elevation of multiple serum markers in patients with stage I ovarian cancer. J Natl Cancer Inst. 1993;85:1748–51.

    Article  PubMed  CAS  Google Scholar 

  28. Yancik R. Ovarian cancer. Age contrasts in incidence, histology, disease stage at diagnosis, and mortality. Cancer. 1993;71:517–23.

    Article  PubMed  CAS  Google Scholar 

  29. Clarke-Pearson DL. Clinical practice. Screening for ovarian cancer. N Engl J Med. 2009;361:170–7.

    Article  PubMed  CAS  Google Scholar 

  30. Neesham D. Ovarian cancer screening. Aust Fam Physician. 2007;36:126–8.

    PubMed  Google Scholar 

  31. Johnson CC, Kessel B, Riley TL, Ragard LR, Williams CR, Xu JL, Buys SS, Prostate, Lung, Colorectal and Ovarian Cancer Project Team. The epidemiology of CA-125 in women without evidence of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial. Gynecol Oncol. 2008;110:383–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. U.S. Preventive Services Task Force. Screening for ovarian cancer: recommendation statement. U.S. Preventive Services Task Force. Am Fam Physician. 2005;71:759–62.

    Google Scholar 

  33. Menon U. Ovarian cancer screening. CMAJ. 2004;171:323–4.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Urban N, McIntosh MW, Andersen M, Karlan BY. Ovarian cancer screening. Hematol Oncol Clin North Am. 2003;17:989–1005, ix.

    Article  PubMed  Google Scholar 

  35. Baron AT, Cora EM, Lafky JM, Boardman CH, Buenafe MC, Rademaker A, Liu D, Fishman DA, Podratz KC, Maihle NJ. Soluble epidermal growth factor receptor (sEGFR/sErbB1) as a potential risk, screening, and diagnostic serum biomarker of epithelial ovarian cancer. Cancer Epidemiol Biomark Prev. 2003;12:103–13.

    CAS  Google Scholar 

  36. Callet N, Delaunay J, Pichon MF. Serum sICAM-1 (soluble intercellular adhesion molecule-1) and M-CSF (macrophage colony-stimulating growth factor) throughout monitoring of 34 non-serous ovarian cancers. Eur J Gynaecol Oncol. 2000;21:135–40.

    PubMed  CAS  Google Scholar 

  37. Crump C, McIntosh MW, Urban N, Anderson G, Karlan BY. Ovarian cancer tumor marker behavior in asymptomatic healthy women: implications for screening. Cancer Epidemiol Biomark Prev. 2000;9:1107–11.

    CAS  Google Scholar 

  38. Oehler MK, Caffier H. Prognostic relevance of serum vascular endothelial growth factor in ovarian cancer. Anticancer Res. 2000;20:5109–12.

    PubMed  CAS  Google Scholar 

  39. Sehouli J, Akdogan Z, Heinze T, Konsgen D, Stengel D, Mustea A, Lichtenegger W. Preoperative determination of CASA (Cancer Associated Serum Antigen) and CA-125 for the discrimination between benign and malignant pelvic tumor mass: a prospective study. Anticancer Res. 2003;23:1115–8.

    PubMed  CAS  Google Scholar 

  40. Suzuki M, Sekiguchi I, Tamada T. Clinical evaluation of tumor-associated mucin-type glycoprotein CA 54/61 in ovarian cancers: comparison with CA 125. Obstet Gynecol. 1990;76:422–7.

    PubMed  CAS  Google Scholar 

  41. Woolas RP, Oram DH, Jeyarajah AR, Bast RC, Jacobs IJ. Ovarian cancer identified through screening with serum markers but not by pelvic imaging. Int J Gynecol Cancer. 1999;9:497–501.

    Article  PubMed  Google Scholar 

  42. Xu Y, Shen Z, Wiper DW, Wu M, Morton RE, Elson P, Kennedy AW, Belinson J, Markman M, Casey G. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. JAMA. 1998;280:719–23.

    Article  PubMed  CAS  Google Scholar 

  43. Yurkovetsky Z, Skates S, Lomakin A, Nolen B, Pulsipher T, Modugno F, Marks J, Godwin A, Gorelik E, Jacobs I, Menon U, Lu K, Badgwell D, Bast RC Jr, Lokshin AE. Development of a multimarker assay for early detection of ovarian cancer. J Clin Oncol. 2010;28:2159–66.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Borgono CA, Grass L, Soosaipillai A, Yousef GM, Petraki CD, Howarth DH, Fracchioli S, Katsaros D, Diamandis EP. Human kallikrein 14: a new potential biomarker for ovarian and breast cancer. Cancer Res. 2003;63:9032–41.

    PubMed  CAS  Google Scholar 

  45. Diamandis EP, Scorilas A, Fracchioli S, Van Gramberen M, De Bruijn H, Henrik A, Soosaipillai A, Grass L, Yousef GM, Stenman UH, Massobrio M, Van Der Zee AG, Vergote I, Katsaros D. Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma. J Clin Oncol. 2003;21:1035–43.

    Article  PubMed  CAS  Google Scholar 

  46. Kishi T, Grass L, Soosaipillai A, Scorilas A, Harbeck N, Schmalfeldt B, Dorn J, Mysliwiec M, Schmitt M, Diamandis EP. Human kallikrein 8, a novel biomarker for ovarian carcinoma. Cancer Res. 2003;63:2771–4.

    PubMed  CAS  Google Scholar 

  47. Kyriakopoulou LG, Yousef GM, Scorilas A, Katsaros D, Massobrio M, Fracchioli S, Diamandis EP. Prognostic value of quantitatively assessed KLK7 expression in ovarian cancer. Clin Biochem. 2003;36:135–43.

    Article  PubMed  CAS  Google Scholar 

  48. Obiezu CV, Scorilas A, Katsaros D, Massobrio M, Yousef GM, Fracchioli S, Rigault de la Longrais IA, Arisio R, Diamandis EP. Higher human kallikrein gene 4 (KLK4) expression indicates poor prognosis of ovarian cancer patients. Clin Cancer Res. 2001;7:2380–6.

    PubMed  CAS  Google Scholar 

  49. Yousef GM, Polymeris ME, Grass L, Soosaipillai A, Chan PC, Scorilas A, Borgono C, Harbeck N, Schmalfeldt B, Dorn J, Schmitt M, Diamandis EP. Human kallikrein 5: a potential novel serum biomarker for breast and ovarian cancer. Cancer Res. 2003;63:3958–65.

    PubMed  CAS  Google Scholar 

  50. Yousef GM, Scorilas A, Katsaros D, Fracchioli S, Iskander L, Borgono C, Rigault de la Longrais IA, Puopolo M, Massobrio M, Diamandis EP. Prognostic value of the human kallikrein gene 15 expression in ovarian cancer. J Clin Oncol. 2003;21:3119–26.

    Article  PubMed  CAS  Google Scholar 

  51. Kim JH, Skates SJ, Uede T, Wong KK, Schorge JO, Feltmate CM, Berkowitz RS, Cramer DW, Mok SC. Osteopontin as a potential diagnostic biomarker for ovarian cancer. JAMA. 2002;287:1671–9.

    Article  PubMed  CAS  Google Scholar 

  52. Mok SC, Chao J, Skates S, Wong K, Yiu GK, Muto MG, Berkowitz RS, Cramer DW. Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology. J Natl Cancer Inst. 2001;93:1458–64.

    Article  PubMed  CAS  Google Scholar 

  53. Schummer M, Ng WV, Bumgarner RE, Nelson PS, Schummer B, Bednarski DW, Hassell L, Baldwin RL, Karlan BY, Hood L. Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene. 1999;238:375–85.

    Article  PubMed  CAS  Google Scholar 

  54. Hogdall C, Fung ET, Christensen IJ, Nedergaard L, Engelholm SA, Petri AL, Risum S, Lundvall L, Yip C, Pedersen AT, Hartwell D, Lomas L, Hogdall EV. A novel proteomic biomarker panel as a diagnostic tool for patients with ovarian cancer. Gynecol Oncol. 2011;123:308–13.

    Article  PubMed  CAS  Google Scholar 

  55. Rice GE, Edgell TA, Autelitano DJ. Evaluation of midkine and anterior gradient 2 in a multimarker panel for the detection of ovarian cancer. J Exp Clin Cancer Res. 2010;29:62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Gorelik E, Landsittel DP, Marrangoni AM, Modugno F, Velikokhatnaya L, Winans MT, Bigbee WL, Herberman RB, Lokshin AE. Multiplexed immunobead-based cytokine profiling for early detection of ovarian cancer. Cancer Epidemiol Biomark Prev. 2005;14:981–7.

    Article  CAS  Google Scholar 

  57. Lambeck AJ, Crijns AP, Leffers N, Sluiter WJ, ten Hoor KA, Braid M, van der Zee AG, Daemen T, Nijman HW, Kast WM. Serum cytokine profiling as a diagnostic and prognostic tool in ovarian cancer: a potential role for interleukin 7. Clin Cancer Res. 2007;13:2385–91.

    Article  PubMed  CAS  Google Scholar 

  58. Yip P, Chen TH, Seshaiah P, Stephen LL, Michael-Ballard KL, Mapes JP, Mansfield BC, Bertenshaw GP. Comprehensive serum profiling for the discovery of epithelial ovarian cancer biomarkers. PLoS One. 2011;6:e29533.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, Hecht JL. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005;65:2162–9.

    Article  PubMed  CAS  Google Scholar 

  60. Schaner ME, Ross DT, Ciaravino G, Sorlie T, Troyanskaya O, Diehn M, Wang YC, Duran GE, Sikic TL, Caldeira S, Skomedal H, Tu IP, Hernandez-Boussard T, Johnson SW, O’Dwyer PJ, Fero MJ, Kristensen GB, Borresen-Dale AL, Hastie T, Tibshirani R, van de Rijn M, Teng NN, Longacre TA, Botstein D, Brown PO, Sikic BI. Gene expression patterns in ovarian carcinomas. Mol Biol Cell. 2003;14:4376–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, Verch T, Steinhoff M, Messerlian G, DiSilvestro P, Granai CO, Bast RC Jr. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008;108:402–8.

    Article  PubMed  CAS  Google Scholar 

  62. Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ, Gajewski W, Kurman R, Bast RC Jr, Skates SJ. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol. 2009;112:40–6.

    Article  PubMed  CAS  Google Scholar 

  63. Pinsky PF, Miller A, Kramer BS, Church T, Reding D, Prorok P, Gelmann E, Schoen RE, Buys S, Hayes RB, Berg CD. Evidence of a healthy volunteer effect in the prostate, lung, colorectal, and ovarian cancer screening trial. Am J Epidemiol. 2007;165:874–81.

    Article  PubMed  CAS  Google Scholar 

  64. Moore RG, Miller MC, Disilvestro P, Landrum LM, Gajewski W, Ball JJ, Skates SJ. Evaluation of the diagnostic accuracy of the risk of ovarian malignancy algorithm in women with a pelvic mass. Obstet Gynecol. 2011;118:280–8.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Ueland FR, Desimone CP, Seamon LG, Miller RA, Goodrich S, Podzielinski I, Sokoll L, Smith A, van Nagell JR Jr, Zhang Z. Effectiveness of a multivariate index assay in the preoperative assessment of ovarian tumors. Obstet Gynecol. 2011;117:1289–97.

    Article  PubMed  Google Scholar 

  66. ACOG. Practice Bulletin No. 174 Summary: evaluation and management of adnexal masses. Obstet Gynecol. 2016;128:1193–5.

    Article  Google Scholar 

  67. van Nagell JR Jr, Miller RW, DeSimone CP, Ueland FR, Podzielinski I, Goodrich ST, Elder JW, Huang B, Kryscio RJ, Pavlik EJ. Long-term survival of women with epithelial ovarian cancer detected by ultrasonographic screening. Obstet Gynecol. 2011;118:1212–21.

    Article  PubMed  Google Scholar 

  68. Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, Amso NN, Apostolidou S, Benjamin E, Cruickshank D, Crump DN, Davies SK, Dawnay A, Dobbs S, Fletcher G, Ford J, Godfrey K, Gunu R, Habib M, Hallett R, Herod J, Jenkins H, Karpinskyj C, Leeson S, Lewis SJ, Liston WR, Lopes A, Mould T, Murdoch J, Oram D, Rabideau DJ, Reynolds K, Scott I, Seif MW, Sharma A, Singh N, Taylor J, Warburton F, Widschwendter M, Williamson K, Woolas R, Fallowfield L, McGuire AJ, Campbell S, Parmar M, Skates SJ. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2016;387:945–56.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Froyman W, Landolfo C, De Cock B, Wynants L, Sladkevicius P, Testa AC, Van Holsbeke C, Domali E, Fruscio R, Epstein E, Dos Santos Bernardo MJ, Franchi D, Kudla MJ, Chiappa V, Alcazar JL, Leone FPG, Buonomo F, Hochberg L, Coccia ME, Guerriero S, Deo N, Jokubkiene L, Kaijser J, Coosemans A, Vergote I, Verbakel JY, Bourne T, Van Calster B, Valentin L, Timmerman D. Risk of complications in patients with conservatively managed ovarian tumours (IOTA5): a 2-year interim analysis of a multicentre, prospective, cohort study. Lancet Oncol. 2019;20:448–58.

    Article  PubMed  Google Scholar 

  70. Partridge E, Kreimer AR, Greenlee RT, Williams C, Xu JL, Church TR, Kessel B, Johnson CC, Weissfeld JL, Isaacs C, Andriole GL, Ogden S, Ragard LR, Buys SS, PLCO Project Team. Results from four rounds of ovarian cancer screening in a randomized trial. Obstet Gynecol. 2009;113:775–82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Buys SS, Partridge E, Greene MH, Prorok PC, Reding D, Riley TL, Hartge P, Fagerstrom RM, Ragard LR, Chia D, Izmirlian G, Fouad M, Johnson CC, Gohagan JK, PLCO Project Team. 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. 2005;193:1630–9.

    Article  PubMed  Google Scholar 

  72. Kobayashi H, Yamada Y, Sado T, Sakata M, Yoshida S, Kawaguchi R, Kanayama S, Shigetomi H, Haruta S, Tsuji Y, Ueda S, Kitanaka T. A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer. 2008;18:414–20.

    Article  PubMed  CAS  Google Scholar 

  73. Einhorn N, Sjovall K, Knapp RC, Hall P, Scully RE, Bast RC Jr, Zurawski VR Jr. Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer. Obstet Gynecol. 1992;80:14–8.

    PubMed  CAS  Google Scholar 

  74. Skates SJ, Xu FJ, Yu YH, Sjovall K, Einhorn N, Chang Y, Bast RC Jr, Knapp RC. Toward an optimal algorithm for ovarian cancer screening with longitudinal tumor markers. Cancer. 1995;76:2004–10.

    Article  PubMed  CAS  Google Scholar 

  75. Skates SJ, Menon U, MacDonald N, Rosenthal AN, Oram DH, Knapp RC, Jacobs IJ. Calculation of the risk of ovarian cancer from serial CA-125 values for preclinical detection in postmenopausal women. J Clin Oncol. 2003;21:206s–10s.

    Article  PubMed  Google Scholar 

  76. Menon U, Skates SJ, Lewis S, Rosenthal AN, Rufford B, Sibley K, Macdonald N, Dawnay A, Jeyarajah A, Bast RC Jr, Oram D, Jacobs IJ. Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer. J Clin Oncol. 2005;23:7919–26.

    Article  PubMed  Google Scholar 

  77. Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, Lewis S, Davies S, Philpott S, Lopes A, Godfrey K, Oram D, Herod J, Williamson K, Seif MW, Scott I, Mould T, Woolas R, Murdoch J, Dobbs S, Amso NN, Leeson S, Cruickshank D, McGuire A, Campbell S, Fallowfield L, Singh N, Dawnay A, Skates SJ, Parmar M, Jacobs I. 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. 2009;10:327–40.

    Article  PubMed  Google Scholar 

  78. Naumann RW, Brown J. Ovarian cancer screening with the Risk of Ovarian Cancer Algorithm (ROCA): good, bad, or just expensive? Gynecol Oncol. 2018;149:117–20.

    Article  PubMed  Google Scholar 

  79. FDA. Ovarian cancer screening tests: safety communication - FDA recommends against use. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm519540.htm.

  80. Greene MH, Piedmonte M, Alberts D, Gail M, Hensley M, Miner Z, Mai PL, Loud J, Rodriguez G, Basil J, Boggess J, Schwartz PE, Kelley JL, Wakeley KE, Minasian L, Skates S. A prospective study of risk-reducing salpingo-oophorectomy and longitudinal CA-125 screening among women at increased genetic risk of ovarian cancer: design and baseline characteristics: a Gynecologic Oncology Group study. Cancer Epidemiol Biomark Prev. 2008;17:594–604.

    Article  Google Scholar 

  81. Anderson GL, McIntosh M, Wu L, Barnett M, Goodman G, Thorpe JD, Bergan L, Thornquist MD, Scholler N, Kim N, O’Briant K, Drescher C, Urban N. Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study. J Natl Cancer Inst. 2010;102:26–38.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. US Preventive Services Task Force Recommendation Statement, Grossman DC, Curry SJ, Owens DK, Barry MJ, Davidson KW, Doubeni CA, Epling JW Jr, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Phipps MG, Silverstein M, Simon MA, Tseng CW. Screening for ovarian cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;319:588–94.

    Article  Google Scholar 

  83. Zhang S, Royer R, Li S, McLaughlin JR, Rosen B, Risch HA, Fan I, Bradley L, Shaw PA, Narod SA. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol. 2011;121:353–7.

    Article  PubMed  CAS  Google Scholar 

  84. Alsop K, Fereday S, Meldrum C, deFazio A, Emmanuel C, George J, Dobrovic A, Birrer MJ, Webb PM, Stewart C, Friedlander M, Fox S, Bowtell D, Mitchell G. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol. 2012;30:2654–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Norquist BM, Harrell MI, Brady MF, Walsh T, Lee MK, Gulsuner S, Bernards SS, Casadei S, Yi Q, Burger RA, Chan JK, Davidson SA, Mannel RS, DiSilvestro PA, Lankes HA, Ramirez NC, King MC, Swisher EM, Birrer MJ. Inherited mutations in women with ovarian carcinoma. JAMA Oncol. 2016;2:482–90.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, Jervis S, van Leeuwen FE, Milne RL, Andrieu N, Goldgar DE, Terry MB, Rookus MA, Easton DF, Antoniou AC, BRCA1 and BRCA2 Cohort Consortium, McGuffog L, Evans DG, Barrowdale D, Frost D, Adlard J, Ong KR, Izatt L, Tischkowitz M, Eeles R, Davidson R, Hodgson S, Ellis S, Nogues C, Lasset C, Stoppa-Lyonnet D, Fricker JP, Faivre L, Berthet P, Hooning MJ, van der Kolk LE, Kets CM, Adank MA, John EM, Chung WK, Andrulis IL, Southey M, Daly MB, Buys SS, Osorio A, Engel C, Kast K, Schmutzler RK, Caldes T, Jakubowska A, Simard J, Friedlander ML, McLachlan SA, Machackova E, Foretova L, Tan YY, Singer CF, Olah E, Gerdes AM, Arver B, Olsson H. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317:2402–16.

    Article  PubMed  CAS  Google Scholar 

  87. NCCN. Genetic/familial high-risk assessment: breast and ovarian. www.nccn.org. Accessed 18 Nov 2019.

  88. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van’t Veer L, Garber JE, Evans G, Isaacs C, Daly MB, Matloff E, Olopade OI, Weber BL, Prevention, Observation of Surgical End Points Study Group. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346:1616–22.

    Article  PubMed  Google Scholar 

  89. Manchanda R, Gaba F. Population based testing for primary prevention: a systematic review. Cancers (Basel). 2018;10(11):424.

    Article  Google Scholar 

  90. Meyer LA, Anderson ME, Lacour RA, Suri A, Daniels MS, Urbauer DL, Nogueras-Gonzalez GM, Schmeler KM, Gershenson DM, Lu KH. Evaluating women with ovarian cancer for BRCA1 and BRCA2 mutations: missed opportunities. Obstet Gynecol. 2010;115:945–52.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Hampel H, Frankel W, Panescu J, Lockman J, Sotamaa K, Fix D, Comeras I, La Jeunesse J, Nakagawa H, Westman JA, Prior TW, Clendenning M, Penzone P, Lombardi J, Dunn P, Cohn DE, Copeland L, Eaton L, Fowler J, Lewandowski G, Vaccarello L, Bell J, Reid G, de la Chapelle A. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res. 2006;66:7810–7.

    Article  PubMed  CAS  Google Scholar 

  92. Domchek S, Robson M. Broadening criteria for BRCA1/2 evaluation: placing the USPSTF recommendation in context. JAMA. 2019;322:619–21.

    Article  PubMed  Google Scholar 

  93. US Preventive Services Task Force Recommendation Statement, Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Doubeni CA, Epling JW Jr, Kubik M, Landefeld CS, Mangione CM, Pbert L, Silverstein M, Simon MA, Tseng CW, Wong JB. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2019;322:652–65.

    Article  Google Scholar 

  94. Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C, Garber JE, Cramer DW, Crum CP. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol. 2006;30:230–6.

    Article  PubMed  Google Scholar 

  95. Piek JM, Kenemans P, Zweemer RP, van Diest PJ, Verheijen RH. Ovarian carcinogenesis, an alternative theory. Gynecol Oncol. 2007;107:355.

    Article  PubMed  Google Scholar 

  96. Crum CP, Drapkin R, Miron A, Ince TA, Muto M, Kindelberger DW, Lee Y. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol. 2007;19:3–9.

    Article  PubMed  Google Scholar 

  97. Chen H, Klein R, Arnold S, Wang Y, Chambers S, Zheng W. Tubal cytology of the fallopian tube as a promising tool for ovarian cancer early detection. J Vis Exp. 2017;(125):55887.

    Google Scholar 

  98. Lum D, Guido R, Rodriguez E, Lee T, Mansuria S, D’Ambrosio L, Austin RM. Brush cytology of the fallopian tube and implications in ovarian cancer screening. J Minim Invasive Gynecol. 2014;21:851–6.

    Article  PubMed  Google Scholar 

  99. Gizzo S, Noventa M, Quaranta M, Vitagliano A, Saccardi C, Litta P, Antona D. A novel hysteroscopic approach for ovarian cancer screening/early diagnosis. Oncol Lett. 2017;13:549–53.

    Article  PubMed  Google Scholar 

  100. Barnabas GD, Bahar-Shany K, Sapoznik S, Helpman L, Kadan Y, Beiner M, Weitzner O, Arbib N, Korach J, Perri T, Katz G, Blecher A, Brandt B, Friedman E, Stockheim D, Jakobson-Setton A, Eitan R, Armon S, Brand H, Zadok O, Aviel-Ronen S, Harel M, Geiger T, Levanon K. Microvesicle proteomic profiling of uterine liquid biopsy for ovarian cancer early detection. Mol Cell Proteomics. 2019;18:865–75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Mao M, Li S, Ren Q, Zhong G, Li R, Chen Y, Jin X, Li J, Ju J, Long G. Development of a blood-based cancer screening assay with a novel multivariate cancer risk score (MCRS) model by integrating shallow WGS data and plasma protein markers. J Glob Oncol. 2019;5:abstr 45.

    Article  Google Scholar 

  102. Oxnard G, Klein E, Seiden M, Hubbell E, Venn O, Jamshidi A, Zhang N, Beausang J, Gross S, Kurtzman K, Fung E, Yecies J, Shaknovich R, Fields A, Sekeres M, Richards D, Yu P, Aravanis A, Hartman A, Liu M. Simultaneous multi-cancer detection and tissue of origin (TOO) localization using targeted bisulfite sequencing of plasma cell-free DNA (cfDNA). J Glob Oncol. 2019;5:abstr 44.

    Article  Google Scholar 

  103. DePriest PD, Varner E, Powell J, Fried A, Puls L, Higgins R, Shenson D, Kryscio R, Hunter JE, Andrews SJ, et al. The efficacy of a sonographic morphology index in identifying ovarian cancer: a multi-institutional investigation. Gynecol Oncol. 1994;55:174–8.

    Article  PubMed  CAS  Google Scholar 

  104. Timmerman D, Testa AC, Bourne T, Ferrazzi E, Ameye L, Konstantinovic ML, Van Calster B, Collins WP, Vergote I, Van Huffel S, Valentin L, International Ovarian Tumor Analysis Group. Logistic regression model to distinguish between the benign and malignant adnexal mass before surgery: a multicenter study by the International Ovarian Tumor Analysis Group. J Clin Oncol. 2005;23:8794–801.

    Article  PubMed  Google Scholar 

  105. Soletormos G, Duffy MJ, Othman Abu Hassan S, Verheijen RH, Tholander B, Bast RC Jr, Gaarenstroom KN, Sturgeon CM, Bonfrer JM, Petersen PH, Troonen H, CarloTorre G, Kanty Kulpa J, Tuxen MK, Molina R. Clinical use of cancer biomarkers in epithelial ovarian cancer: updated guidelines from the European Group on Tumor Markers. Int J Gynecol Cancer. 2016;26:43–51.

    Article  PubMed  Google Scholar 

  106. Bailey J, Tailor A, Naik R, Lopes A, Godfrey K, Hatem HM, Monaghan J. Risk of malignancy index for referral of ovarian cancer cases to a tertiary center: does it identify the correct cases? Int J Gynecol Cancer. 2006;16(Suppl 1):30–4.

    Article  PubMed  Google Scholar 

  107. Enakpene CA, Omigbodun AO, Goecke TW, Odukogbe AT, Beckmann MW. Preoperative evaluation and triage of women with suspicious adnexal masses using risk of malignancy index. J Obstet Gynaecol Res. 2009;35:131–8.

    Article  PubMed  Google Scholar 

  108. Tingulstad S, Hagen B, Skjeldestad FE, Onsrud M, Kiserud T, Halvorsen T, Nustad K. Evaluation of a risk of malignancy index based on serum CA125, ultrasound findings and menopausal status in the pre-operative diagnosis of pelvic masses. Br J Obstet Gynaecol. 1996;103:826–31.

    Article  PubMed  CAS  Google Scholar 

  109. Tingulstad S, Skjeldestad FE, Hagen B. The effect of centralization of primary surgery on survival in ovarian cancer patients. Obstet Gynecol. 2003;102:499–505.

    PubMed  Google Scholar 

  110. Geomini P, Kruitwagen R, Bremer GL, Cnossen J, Mol BW. The accuracy of risk scores in predicting ovarian malignancy: a systematic review. Obstet Gynecol. 2009;113:384–94.

    Article  PubMed  Google Scholar 

  111. Moore RG, Maclaughlan S. Current clinical use of biomarkers for epithelial ovarian cancer. Curr Opin Oncol. 2010;22:492–7.

    Article  PubMed  CAS  Google Scholar 

  112. Van Gorp T, Veldman J, Van Calster B, Cadron I, Leunen K, Amant F, Timmerman D, Vergote I. Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses. Eur J Cancer. 2012;48:1649–56.

    Article  PubMed  Google Scholar 

  113. Abdel-Azeez HA, Labib HA, Sharaf SM, Refai AN. HE4 and mesothelin: novel biomarkers of ovarian carcinoma in patients with pelvic masses. Asian Pac J Cancer Prev. 2010;11:111–6.

    PubMed  Google Scholar 

  114. Chang X, Ye X, Dong L, Cheng H, Cheng Y, Zhu L, Liao Q, Zhao Y, Tian L, Fu T, Chen J, Cui H. Human epididymis protein 4 (HE4) as a serum tumor biomarker in patients with ovarian carcinoma. Int J Gynecol Cancer. 2011;21:852–8.

    Article  PubMed  Google Scholar 

  115. Holcomb K, Vucetic Z, Miller MC, Knapp RC. Human epididymis protein 4 offers superior specificity in the differentiation of benign and malignant adnexal masses in premenopausal women. Am J Obstet Gynecol. 2011;205(358):e1–6.

    Google Scholar 

  116. Huhtinen K, Suvitie P, Hiissa J, Junnila J, Huvila J, Kujari H, Setala M, Harkki P, Jalkanen J, Fraser J, Makinen J, Auranen A, Poutanen M, Perheentupa A. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer. 2009;100:1315–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Kadija S, Stefanovic A, Jeremic K, Radojevic MM, Nikolic L, Markovic I, Atanackovic J. The utility of human epididymal protein 4, cancer antigen 125, and risk for malignancy algorithm in ovarian cancer and endometriosis. Int J Gynecol Cancer. 2012;22:238–44.

    Article  PubMed  Google Scholar 

  118. Kim YM, Whang DH, Park J, Kim SH, Lee SW, Park HA, Ha M, Choi KH. Evaluation of the accuracy of serum human epididymis protein 4 in combination with CA125 for detecting ovarian cancer: a prospective case-control study in a Korean population. Clin Chem Lab Med. 2011;49:527–34.

    Article  PubMed  CAS  Google Scholar 

  119. Ruggeri G, Bandiera E, Zanotti L, Belloli S, Ravaggi A, Romani C, Bignotti E, Tassi RA, Tognon G, Galli C, Caimi L, Pecorelli S. HE4 and epithelial ovarian cancer: comparison and clinical evaluation of two immunoassays and a combination algorithm. Clin Chim Acta. 2011;412:1447–53.

    Article  PubMed  CAS  Google Scholar 

  120. Van Gorp T, Cadron I, Despierre E, Daemen A, Leunen K, Amant F, Timmerman D, De Moor B, Vergote I. HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm. Br J Cancer. 2011;104:863–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Montagnana M, Danese E, Ruzzenente O, Bresciani V, Nuzzo T, Gelati M, Salvagno GL, Franchi M, Lippi G, Guidi GC. The ROMA (Risk of Ovarian Malignancy Algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it really useful? Clin Chem Lab Med. 2011;49:521–5.

    Article  PubMed  CAS  Google Scholar 

  122. Jacob F, Meier M, Caduff R, Goldstein D, Pochechueva T, Hacker N, Fink D, Heinzelmann-Schwarz V. No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting. Gynecol Oncol. 2011;121:487–91.

    Article  PubMed  CAS  Google Scholar 

  123. Zhang Z, Chan DW. The road from discovery to clinical diagnostics: lessons learned from the first FDA-cleared in vitro diagnostic multivariate index assay of proteomic biomarkers. Cancer Epidemiol Biomark Prev. 2010;19:2995–9.

    Article  CAS  Google Scholar 

  124. Ware Miller R, Smith A, DeSimone CP, Seamon L, Goodrich S, Podzielinski I, Sokoll L, van Nagell JR Jr, Zhang Z, Ueland FR. Performance of the American College of Obstetricians and Gynecologists’ ovarian tumor referral guidelines with a multivariate index assay. Obstet Gynecol. 2011;117:1298–306.

    Article  Google Scholar 

  125. Timmerman D, Van Calster B, Vergote I, Van Hoorde K, Van Gorp T, Valentin L, Bourne T. Performance of the American College of Obstetricians and Gynecologists’ ovarian tumor referral guidelines with a multivariate index assay. Obstet Gynecol. 2011;118:1179–81; author reply 1181.

    Article  PubMed  Google Scholar 

  126. Moore LE, Pfeiffer RM, Zhang Z, Lu KH, Fung ET, Bast RC Jr. Proteomic biomarkers in combination with CA 125 for detection of epithelial ovarian cancer using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Cancer. 2012;118:91–100.

    Article  PubMed  CAS  Google Scholar 

  127. Cramer DW, Bast RC Jr, Berg CD, Diamandis EP, Godwin AK, Hartge P, Lokshin AE, Lu KH, McIntosh MW, Mor G, Patriotis C, Pinsky PF, Thornquist MD, Scholler N, Skates SJ, Sluss PM, Srivastava S, Ward DC, Zhang Z, Zhu CS, Urban N. Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res (Phila). 2011;4:365–74.

    Article  Google Scholar 

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  1. The James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA

    Monica Levine MD

  2. Levine Cancer Institute, Atrium Health, Charlotte, NC, USA

    R. Wendel Naumann MD

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    Samir A. Farghaly

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Levine, M., Naumann, R.W. (2022). Ovarian Cancer Screening and Early Detection. In: Farghaly, S.A. (eds) Advances in Diagnosis and Management of Ovarian Cancer. Springer, Cham. https://doi.org/10.1007/978-3-031-09169-8_2

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