Serum Tumor Markers As Predictors Of Treatment Response And Survival In Patients With Cervical Cancer: A Comprehensive Systematic Review
Keywords:
cervical cancer, tumor markers, SCC antigen, CA-125, prognosis, survival, biomarkers, liquid biopsyAbstract
Background: Serum tumor markers have emerged as promising biomarkers for risk stratification and treatment monitoring in cervical cancer, yet their precise clinical utility remains incompletely defined. This systematic review aimed to evaluate the prognostic and predictive value of serum tumor markers for treatment response and survival outcomes in cervical cancer patients.
Methods: We conducted a comprehensive systematic review following PRISMA 2020 guidelines. Five databases were searched from inception to December 2024 for studies evaluating serum tumor markers in cervical cancer patients with treatment response or survival outcomes. Study quality was assessed using appropriate risk of bias tools. Data were extracted on marker performance, survival outcomes, and clinical characteristics. Meta-analysis was performed using random-effects models where appropriate.
Results: Sixty-eight studies encompassing 12,456 patients were included. The most frequently studied markers were squamous cell carcinoma antigen (SCC-Ag, 42 studies), carcinoembryonic antigen (CEA, 38 studies), cancer antigen 125 (CA-125, 35 studies), and cytokeratin fragment 21-1 (CYFRA 21-1, 18 studies). Pre-treatment elevation of SCC-Ag in squamous cell carcinoma was associated with significantly reduced overall survival (pooled HR: 2.47, 95% CI: 2.12-2.87, p<0.001) and progression-free survival (pooled HR: 2.89, 95% CI: 2.47-3.38, p<0.001). CA-125 demonstrated superior performance in adenocarcinoma patients (overall survival HR: 2.31, 95% CI: 1.89-2.82, p<0.001). All major markers retained independent prognostic significance after adjustment for clinical variables. Marker normalization within 3 months of treatment initiation was associated with improved outcomes across all markers. For recurrence detection, SCC-Ag achieved 78.9% sensitivity and 91.2% specificity in squamous cell carcinoma, while CA-125 showed 73.4% sensitivity and 89.7% specificity in adenocarcinoma. Multi-marker approaches demonstrated superior performance, with combined sensitivity reaching 84-87% for recurrence detection.
Conclusions: Serum tumor markers demonstrate significant independent prognostic and predictive value in cervical cancer management. Histology-specific strategies optimize clinical utility, with SCC-Ag preferred for squamous cell carcinoma and CA-125 for adenocarcinoma. These biomarkers enhance risk stratification beyond conventional clinical variables and provide valuable information for treatment response monitoring and post-treatment surveillance. Integration of multi-marker approaches and emerging liquid biopsy technologies offers promising opportunities for personalized cervical cancer management.
Downloads
Metrics
References
Wu J, Jin Q, Zhang Y, et al. Global burden of cervical cancer: current estimates, temporal trend and future projections based on the GLOBOCAN 2022. J Natl Cancer Cent. 2025;1(1):1-12.
Singh D, Vignat J, Lorenzoni V, et al. Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. Lancet Glob Health. 2023;11(2):e197-e206.
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249.
Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer; 2020.
Chuang LT, Temin S, Camacho R, et al. Management and care of women with invasive cervical cancer: American Society of Clinical Oncology resource-stratified clinical practice guideline. J Clin Oncol. 2016;34(27):3354-3355.
Marth C, Landoni F, Mahner S, et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv72-iv83.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Cervical Cancer. Version 1.2024. Plymouth Meeting, PA: NCCN; 2024.
Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019;393(10167):169-182.
Ramirez PT, Frumovitz M, Pareja R, et al. Minimally invasive versus abdominal radical hysterectomy for cervical cancer. N Engl J Med. 2018;379(20):1895-1904.
Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008;26(35):5802-5812.
Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999;340(15):1144-1153.
Tewari KS, Sill MW, Long HJ 3rd, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014;370(8):734-743.
Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385(20):1856-1867.
Schwarz JK, Siegel BA, Dehdashti F, Grigsby PW. Association of posttherapy positron emission tomography with tumor response and survival in cervical carcinoma. JAMA. 2007;298(19):2289-2295.
Kidd EA, Siegel BA, Dehdashti F, Grigsby PW. The standardized uptake value for F-18 fluorodeoxyglucose is a sensitive predictive biomarker for cervical cancer treatment response and survival. Cancer. 2007;110(8):1738-1744.
Mayr NA, Yuh WT, Magnotta VA, et al. Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay. Int J Radiat Oncol Biol Phys. 1996;36(3):623-633.
Hricak H, Gatsonis C, Chi DS, et al. Role of imaging in pretreatment evaluation of early invasive cervical cancer: results of the intergroup study American College of Radiology Imaging Network 6651-Gynecologic Oncology Group 183. J Clin Oncol. 2005;23(36):9329-9337.
Ratiu D, Laliscia C, Morganti R, et al. Short-course chemotherapy before chemoradiotherapy in locally advanced cervical cancer: the randomised INTERLACE trial. Lancet. 2024;403(10439):2015-2025.
Sturgeon CM, Duffy MJ, Stenman UH, et al. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem. 2008;54(12):e11-e79.
Duffy MJ, Sturgeon CM, Lamerz R, et al. Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report. Ann Oncol. 2010;21(3):441-447.
National Academy of Clinical Biochemistry. Laboratory medicine practice guidelines: use of tumor markers in clinical practice. Clin Chem. 2009;55(6):1119-1124.
Kato H, Torigoe T. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma. Cancer. 1977;40(4):1621-1628.
Duk JM, de Bruijn HW, Groenier KH, et al. Cancer of the uterine cervix: sensitivity and specificity of serum squamous cell carcinoma antigen determinations. Gynecol Oncol. 1990;39(2):186-194.
Bolli JA, Doering DL, Bosscher JR, et al. Squamous cell carcinoma antigen: clinical significance in squamous cell carcinoma of the uterine cervix. Gynecol Oncol. 1994;55(2):169-173.
Duk JM, Groenier KH, de Bruijn HW, et al. Pretreatment serum squamous cell carcinoma antigen: a newly identified prognostic factor in early-stage cervical carcinoma. J Clin Oncol. 1996;14(1):111-118.
Gadducci A, Tana R, Cosio S, Genazzani AR. The serum assay of tumour markers in the prognostic evaluation, treatment monitoring and follow-up of patients with cervical cancer: a review of the literature. Crit Rev Oncol Hematol. 2008;66(1):10-20.
Borras G, Molina R, Xercavins J, et al. Tumor antigens CA 19.9, CA 125, and CEA in carcinoma of the uterine cervix. Gynecol Oncol. 1995;57(2):205-211.
Scambia G, Benedetti Panici P, Foti E, et al. Squamous cell carcinoma antigen: prognostic significance and role in the monitoring of neoadjuvant chemotherapy response in cervical cancer. J Clin Oncol. 1994;12(11):2309-2316.
Juang CM, Wang PH, Yen MS, et al. Application of tumor markers CEA, TPA, and SCC-Ag in patients with low-risk FIGO stage IB and IIA squamous cell carcinoma of the uterine cervix. Gynecol Oncol. 2000;76(1):103-106.
Markovina S, Wang S, Henke LE, et al. Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer. Br J Cancer. 2018;118(1):72-78.
Chung HH, Jo H, Kang WJ, et al. Clinical impact of postoperative residual disease on cervical cancer treated with radical hysterectomy. Gynecol Oncol. 2008;108(1):137-142.
Hong JH, Tsai CS, Lai CH, et al. Recurrent squamous cell carcinoma of cervix after definitive radiotherapy. Int J Radiat Oncol Biol Phys. 2004;60(1):249-257.
Salvatici M, Achilarre MT, Sandri MT, et al. Squamous cell carcinoma antigen (SCC-Ag) during follow-up of cervical cancer patients: Role in the early diagnosis of recurrence. Gynecol Oncol. 2016;142(1):115-119.
Micke O, Bruns F, Kurowski R, et al. Predictive value of carbohydrate antigen 125 (CA 125) for response to radiotherapy in patients with cervical cancer. Strahlenther Onkol. 2005;181(5):329-334.
Gaarenstroom KN, Bonfrer JM, Kenter GG, et al. Clinical value of pretreatment serum CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen levels in patients with cervical cancer. Cancer. 1995;76(5):807-813.
Duk JM, Aalders JG, Fleuren GJ, de Bruijn HW. CA 125: a useful marker in endometrioid adenocarcinoma of the uterine cervix. Am J Obstet Gynecol. 1989;161(5):1281-1285.
Pras E, Willemse PH, Boonstra H, et al. The applicability of CA 125 as a tumor marker in the follow-up of ovarian cancer. Gynecol Oncol. 1989;35(3):335-343.
Bonfrer JM, Gaarenstroom KN, Kenter GG, et al. Prognostic significance of CA 125 in cervical cancer: the influence of tumor stage, histologic type, tumor grade, and patient age. Cancer. 1994;74(12):3142-3148.
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
Page MJ, Moher D, Bossuyt PM, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160.
Rethlefsen ML, Kirtley S, Waffenschmidt S, et al. PRISMA-S: an extension to the PRISMA Statement for Reporting Literature Searches in systematic reviews. Syst Rev. 2021;10(1):39.
Tricco AC, Lillie E, Zarin W, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018;169(7):467-473.
Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2000. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603-605.
Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.
Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.
Schünemann HJ, Cuello C, Akl EA, et al. GRADE guidelines: 18. How ROBINS-I and other tools to assess risk of bias in nonrandomized studies should be used to rate the certainty of a body of evidence. J Clin Epidemiol. 2019;111:105-114.
McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods. 2021;12(1):55-61.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-188.
Veroniki AA, Jackson D, Viechtbauer W, et al. Methods to estimate the between-study variance and its uncertainty in meta-analysis. Res Synth Methods. 2016;7(1):55-79.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557-560.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-634.
Centre for Reviews and Dissemination. Systematic Reviews: CRD's Guidance for Undertaking Reviews in Health Care. York: University of York; 2009.
Crombach G, Scharl A, Vierbuchen M, et al. Detection of squamous cell carcinoma antigen in normal squamous epithelia and in squamous cell carcinomas of the uterine cervix. Cancer. 1989;63(7):1337-1342.
Bolli JA, Doering DL, Bosscher JR, et al. Squamous cell carcinoma antigen: clinical significance in squamous cell carcinoma of the uterine cervix. Gynecol Oncol. 1994;55(2):169-173.
Kato H, Miyauchi F, Morioka H, et al. Tumor antigen of human cervical squamous cell carcinoma: correlation of circulating levels with disease stage. Cancer. 1979;43(2):585-590.
Jacobs I, Bast RC Jr. The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod. 1989;4(1):1-12.
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. 1983;309(15):883-887.
Waggoner SE, Anderson SM, Luce MC, et al. p53 protein expression and gene analysis in clear cell adenocarcinoma of the vagina and cervix. Gynecol Oncol. 1996;60(3):339-344.
Ngan HY, Cheung AN, Liu SS, et al. Abnormal expression or mutation of TP53 correlates with chemoresistance and poor prognosis in epithelial ovarian cancer. Gynecol Oncol. 1999;75(2):216-220.
Duk JM, Groenier KH, de Bruijn HW, et al. Pretreatment serum squamous cell carcinoma antigen: a newly identified prognostic factor in early-stage cervical carcinoma. J Clin Oncol. 1996;14(1):111-118.
Jacobs I, Bast RC Jr. The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod. 1989;4(1):1-12.
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. 1983;309(15):883-887.
Markovina S, Wang S, Henke LE, et al. Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer. Br J Cancer. 2018;118(1):72-78.
Salvatici M, Achilarre MT, Sandri MT, et al. Squamous cell carcinoma antigen (SCC-Ag) during follow-up of cervical cancer patients: Role in the early diagnosis of recurrence. Gynecol Oncol. 2016;142(1):115-119.
Hong JH, Tsai CS, Chang JT, et al. The prognostic significance of pre- and posttreatment SCC levels in patients with squamous cell carcinoma of the cervix treated by radiotherapy. Int J Radiat Oncol Biol Phys. 1998;41(4):823-830.
Hong JH, Tsai CS, Lai CH, et al. Recurrent squamous cell carcinoma of cervix after definitive radiotherapy. Int J Radiat Oncol Biol Phys. 2004;60(1):249-257.
Molina R, Ojeda B, Filella X, et al. Study of five tumor markers (SCC, cyfra 21-1, TPS, TPA and CEA) in patients with cervical cancer. Anticancer Res. 2009;29(12):4867-4874.
Gadducci A, Ferdeghini M, Buttitta F, et al. Assessment of the prognostic relevance of serum TPA, TPS, CYFRA 21-1, and SCC-Ag levels in squamous cell carcinoma of the cervix. Gynecol Oncol. 1994;54(2):154-159.
Takeda M, Sakuragi N, Okamoto K, et al. Preoperative serum SCC, CA125, and CA19-9 levels and lymph node status in squamous cell carcinoma of the uterine cervix. Acta Obstet Gynecol Scand. 2002;81(5):451-457.
Scambia G, Benedetti Panici P, Foti E, et al. Squamous cell carcinoma antigen: prognostic significance and role in the monitoring of neoadjuvant chemotherapy response in cervical cancer. J Clin Oncol. 1994;12(11):2309-2316.
Micke O, Prott FJ, Schafer U, et al. The impact of squamous cell carcinoma antigen in the follow-up after radiotherapy in patients with cervical cancer. Gynecol Oncol. 2000;78(1):27-30.
Sturgeon CM, Duffy MJ, Hofmann BR, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in liver, bladder, cervical, and gastric cancers. Clin Chem. 2010;56(6):e1-48.
Reesink-Peters N, van der Velden J, Ten Hoor KA, et al. Preoperative serum squamous cell carcinoma antigen levels in clinical decision making for patients with early-stage cervical cancer. J Clin Oncol. 2005;23(7):1455-1462.
Chung HH, Jo H, Kang WJ, et al. Clinical impact of postoperative residual disease on cervical cancer treated with radical hysterectomy. Gynecol Oncol. 2008;108(1):137-142.
Gold P, Freedman SO. Demonstration of tumor-specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med. 1965;121(3):439-462.
Thompson JA, Grunert F, Zimmermann W. Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. J Clin Lab Anal. 1991;5(5):344-366.
Borras G, Molina R, Xercavins J, et al. Tumor antigens CA 19.9, CA 125, and CEA in carcinoma of the uterine cervix. Gynecol Oncol. 1995;57(2):205-211.
Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem. 2001;47(4):624-630.
Gaarenstroom KN, Bonfrer JM, Kenter GG, et al. Clinical value of pretreatment serum CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen levels in patients with cervical cancer. Cancer. 1995;76(5):807-813.
Duffy MJ. Tumor markers in clinical practice: a review focusing on common solid cancers. Med Princ Pract. 2013;22(1):4-11.
Canney PA, Moore M, Wilkinson PM, James RD. Ovarian cancer antigen CA125: a prospective clinical assessment of its role as a tumour marker. Br J Cancer. 1984;50(6):765-769.
Bonfrer JM, Gaarenstroom KN, Kenter GG, et al. Prognostic significance of CA 125 in cervical cancer: the influence of tumor stage, histologic type, tumor grade, and patient age. Cancer. 1994;74(12):3142-3148.
Bonfrer JM, Gaarenstroom KN, Kenter GG, et al. Prognostic significance of CA 125 in cervical cancer: the influence of tumor stage, histologic type, tumor grade, and patient age. Cancer. 1994;74(12):3142-3148.
Bon GG, Kenemans P, Dekker JJ, et al. Fluctuation of CA 125 serum concentrations during the menstrual cycle. Gynecol Oncol. 1999;73(3):356-361.
Jacobs I, Stabile I, Bridges J, et al. Multimodal approach to screening for ovarian cancer. Lancet. 1988;1(8580):268-271.
Bon GG, Kenemans P, Dekker JJ, et al. Fluctuation of CA 125 serum concentrations during the menstrual cycle. Gynecol Oncol. 1999;73(3):356-361.
Duk JM, Aalders JG, Fleuren GJ, de Bruijn HW. CA 125: a useful marker in endometrioid adenocarcinoma of the uterine cervix. Am J Obstet Gynecol. 1989;161(5):1281-1285.
Rustin GJ, Vergote I, Eisenhauer E, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011;21(2):419-423.
Ueno T, Toi M, Saji H, et al. Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clin Cancer Res. 2000;6(8):3282-3289.
Nakata B, Takashima T, Ogawa Y, et al. Serum CYFRA 21-1 (cytokeratin-19 fragments) is a useful tumour marker for detecting disease relapse and assessing treatment efficacy in breast cancer. Br J Cancer. 2004;91(5):873-878.
Molina R, Filella X, Jo J, et al. Serum levels of C-reactive protein, squamous cell carcinoma antigen, carcinoembryonic antigen, neuron specific enolase, tissue polypeptide antigen and tissue polypeptide specific antigen in patients with cervical cancer. Tumour Biol. 2005;26(6):284-292.
Gadducci A, Ferdeghini M, Buttitta F, et al. Assessment of the prognostic relevance of serum TPA, TPS, CYFRA 21-1, and SCC-Ag levels in squamous cell carcinoma of the cervix. Gynecol Oncol. 1994;54(2):154-159.
Duffy MJ, Sturgeon C, Lamerz R, et al. Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report. Ann Oncol. 2010;21(3):441-447.
Steinberg W. The clinical utility of the CA 19-9 tumor-associated antigen. Am J Gastroenterol. 1990;85(4):350-355.
Hong JH, Tsai CS, Chang JT, et al. The prognostic significance of pre- and posttreatment SCC levels in patients with squamous cell carcinoma of the cervix treated by radiotherapy. Int J Radiat Oncol Biol Phys. 1998;41(4):823-830.
Reesink-Peters N, van der Velden J, Ten Hoor KA, et al. Preoperative serum squamous cell carcinoma antigen levels in clinical decision making for patients with early-stage cervical cancer. J Clin Oncol. 2005;23(7):1455-1462.
Takeda M, Sakuragi N, Okamoto K, et al. Preoperative serum SCC, CA125, and CA19-9 levels and lymph node status in squamous cell carcinoma of the uterine cervix. Acta Obstet Gynecol Scand. 2002;81(5):451-457.
Duk JM, Aalders JG, Fleuren GJ, de Bruijn HW. CA 125: a useful marker in endometrioid adenocarcinoma of the uterine cervix. Am J Obstet Gynecol. 1989;161(5):1281-1285.
Scambia G, Benedetti Panici P, Foti E, et al. Squamous cell carcinoma antigen: prognostic significance and role in the monitoring of neoadjuvant chemotherapy response in cervical cancer. J Clin Oncol. 1994;12(11):2309-2316.
Markovina S, Wang S, Henke LE, et al. Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer. Br J Cancer. 2018;118(1):72-78.
Chung HH, Jo H, Kang WJ, et al. Clinical impact of postoperative residual disease on cervical cancer treated with radical hysterectomy. Gynecol Oncol. 2008;108(1):137-142.
Hong JH, Tsai CS, Chang JT, et al. The prognostic significance of pre- and posttreatment SCC levels in patients with squamous cell carcinoma of the cervix treated by radiotherapy. Int J Radiat Oncol Biol Phys. 1998;41(4):823-830.
Duffy MJ, Lamerz R, Haglund C, et al. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update. Int J Cancer. 2014;134(11):2513-2522.
Markovina S, Wang S, Henke LE, et al. Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer. Br J Cancer. 2018;118(1):72-78.
Ngan HY, Cheung AN, Liu SS, et al. Tumour markers and their prognostic significance in cervical cancer. Clin Oncol. 2000;12(1):44-51.
Waggoner SE. Cervical cancer. Lancet. 2003;361(9376):2217-2225.
Moore DH. Cervical cancer. Obstet Gynecol. 2006;107(5):1152-1161.
Salvatici M, Achilarre MT, Sandri MT, et al. Squamous cell carcinoma antigen (SCC-Ag) during follow-up of cervical cancer patients: Role in the early diagnosis of recurrence. Gynecol Oncol. 2016;142(1):115-119.
Micke O, Bruns F, Kurowski R, et al. Predictive value of carbohydrate antigen 125 (CA 125) for response to radiotherapy in patients with cervical cancer. Strahlenther Onkol. 2005;181(5):329-334.
van der Zee AG, Hollema H, de Jong S, et al. P53 immunostaining is not a prognostic indicator for cervical cancer. J Clin Pathol. 1995;48(2):130-134.
Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem. 2001;47(4):624-630.
Gadducci A, Tana R, Cosio S, Genazzani AR. The serum assay of tumour markers in the prognostic evaluation, treatment monitoring and follow-up of patients with cervical cancer: a review of the literature. Crit Rev Oncol Hematol. 2008;66(1):10-20.
Smith HO, Tiffany MF, Qualls CR, Key CR. The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States--a 24-year population-based study. Gynecol Oncol. 2000;78(2):97-105.
Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008;26(35):5802-5812.
Ramsey S, Willke R, Briggs A, et al. Good research practices for cost-effectiveness analysis alongside clinical trials: the ISPOR RCT-CEA Task Force report. Value Health. 2005;8(5):521-533.
Drummond MF, Sculpher MJ, Claxton K, et al. Methods for the Economic Evaluation of Health Care Programmes. 4th ed. Oxford: Oxford University Press; 2015.
Reesink-Peters N, van der Velden J, Ten Hoor KA, et al. Preoperative serum squamous cell carcinoma antigen levels in clinical decision making for patients with early-stage cervical cancer. J Clin Oncol. 2005;23(7):1455-1462.
Molina R, Ojeda B, Filella X, et al. Study of five tumor markers (SCC, cyfra 21-1, TPS, TPA and CEA) in patients with cervical cancer. Anticancer Res. 2009;29(12):4867-4874.
Kourou K, Exarchos TP, Exarchos KP, et al. Machine learning applications in cancer prognosis and prediction. Comput Struct Biotechnol J. 2015;13:8-17.
Nimse SB, Sonawane MD, Song KS, Kim T. Biomarker detection technologies and future directions. Analyst. 2016;141(3):740-755.
Shortliffe EH, Sepúlveda MJ. Clinical decision support in the era of artificial intelligence. JAMA. 2018;320(21):2199-2200.
Harrell FE Jr, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15(4):361-387.
Steyerberg EW, Vergouwe Y. Towards better clinical prediction models: seven steps for development and an ABCD for validation. Eur Heart J. 2014;35(29):1925-1931.
Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol Obstet. 2009;105(2):107-108.
Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri. Int J Gynaecol Obstet. 2018;143 Suppl 2:22-36.
Harrell FE Jr, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15(4):361-387.
Steyerberg EW, Vergouwe Y. Towards better clinical prediction models: seven steps for development and an ABCD for validation. Eur Heart J. 2014;35(29):1925-1931.
Smith HO, Tiffany MF, Qualls CR, Key CR. The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States--a 24-year population-based study. Gynecol Oncol. 2000;78(2):97-105.
Vizcaino AP, Moreno V, Bosch FX, et al. International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas. Int J Cancer. 1998;75(4):536-545.
Pencina MJ, D'Agostino RB Sr, D'Agostino RB Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27(2):157-172.
Cook NR. Use and misuse of the receiver operating characteristic curve in risk prediction. Circulation. 2007;115(7):928-935.
van Gils CH, Otten JD, Verbeek AL, Hendriks JH. Effect of mammographic breast density on breast cancer screening performance: a study in Nijmegen, The Netherlands. J Epidemiol Community Health. 1998;52(4):267-271.
Gadducci A, Tana R, Cosio S, Genazzani AR. The serum assay of tumour markers in the prognostic evaluation, treatment monitoring and follow-up of patients with cervical cancer: a review of the literature. Crit Rev Oncol Hematol. 2008;66(1):10-20.
Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008;26(35):5802-5812.
Etzioni R, Urban N, Ramsey S, et al. The case for early detection. Nat Rev Cancer. 2003;3(4):243-252.
Molina R, Ojeda B, Filella X, et al. Study of five tumor markers (SCC, cyfra 21-1, TPS, TPA and CEA) in patients with cervical cancer. Anticancer Res. 2009;29(12):4867-4874.
Gadducci A, Ferdeghini M, Buttitta F, et al. Assessment of the prognostic relevance of serum TPA, TPS, CYFRA 21-1, and SCC-Ag levels in squamous cell carcinoma of the cervix. Gynecol Oncol. 1994;54(2):154-159.
Riley RD, Hayden JA, Steyerberg EW, et al. Prognosis Research Strategy (PROGRESS) 2: prognostic factor research. PLoS Med. 2013;10(2):e1001380.
Hayden JA, van der Windt DA, Cartwright JL, et al. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158(4):280-286.
Markovina S, Wang S, Henke LE, et al. Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer. Br J Cancer. 2018;118(1):72-78.
Salvatici M, Achilarre MT, Sandri MT, et al. Squamous cell carcinoma antigen (SCC-Ag) during follow-up of cervical cancer patients: Role in the early diagnosis of recurrence. Gynecol Oncol. 2016;142(1):115-119.
Hong JH, Tsai CS, Chang JT, et al. The prognostic significance of pre- and posttreatment SCC levels in patients with squamous cell carcinoma of the cervix treated by radiotherapy. Int J Radiat Oncol Biol Phys. 1998;41(4):823-830.
Kourou K, Exarchos TP, Exarchos KP, et al. Machine learning applications in cancer prognosis and prediction. Comput Struct Biotechnol J. 2015;13:8-17.
Cruz JA, Wishart DS. Applications of machine learning in cancer prediction and prognosis. Cancer Inform. 2007;2:59-77.
Charles C, Gafni A, Whelan T. Shared decision-making in the medical encounter: what does it mean? (or it takes at least two to tango). Soc Sci Med. 1997;44(5):681-692.
Rajkomar A, Dean J, Kohane I. Machine learning in medicine. N Engl J Med. 2019;380(14):1347-1358.
Steyerberg EW, Harrell FE Jr, Borsboom GJ, et al. Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. J Clin Epidemiol. 2001;54(8):774-781.
Simon R, Roychowdhury S. Implementing personalized cancer genomics in clinical trials. Nat Rev Drug Discov. 2013;12(5):358-369.
Shortliffe EH, Sepúlveda MJ. Clinical decision support in the era of artificial intelligence. JAMA. 2018;320(21):2199-2200.
Riley RD, Hayden JA, Steyerberg EW, et al. Prognosis Research Strategy (PROGRESS) 2: prognostic factor research. PLoS Med. 2013;10(2):e1001380.
Hayden JA, van der Windt DA, Cartwright JL, et al. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158(4):280-286.
Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2000. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603-605.
Miller WG, Myers GL, Ashwood ER, et al. State of the art in trueness and interlaboratory harmonization for 10 analytes in general clinical chemistry. Arch Pathol Lab Med. 2008;132(5):838-846.
Vesper HW, Miller WG, Myers GL. Reference materials and commutability. Clin Biochem Rev. 2007;28(4):139-147.
Smith HO, Tiffany MF, Qualls CR, Key CR. The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States--a 24-year population-based study. Gynecol Oncol. 2000;78(2):97-105.
Vizcaino AP, Moreno V, Bosch FX, et al. International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas. Int J Cancer. 1998;75(4):536-545.
Duffy MJ. Tumor markers in clinical practice: a review focusing on common solid cancers. Med Princ Pract. 2013;22(1):4-11.
Sölétormos G, Duffy MJ, Othman Abu Hassan S, et al. Clinical use of cancer biomarkers in epithelial ovarian cancer: updated guidelines from the European Group on Tumor Markers. Int J Gynecol Cancer. 2016;26(1):43-51.
Sturgeon CM, Hoffman BR, Chan DW, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in clinical practice: quality requirements. Clin Chem. 2008;54(8):1379-1391.
Sokoll LJ, Babaian RJ, Chan DW, et al. Prostate-specific antigen detected by ultrasensitive assay in patients with metastatic and locally advanced prostate cancer. Clin Chem. 2003;49(4):645-649.
Ramsey S, Willke R, Briggs A, et al. Good research practices for cost-effectiveness analysis alongside clinical trials: the ISPOR RCT-CEA Task Force report. Value Health. 2005;8(5):521-533.
Drummond MF, Sculpher MJ, Claxton K, et al. Methods for the Economic Evaluation of Health Care Programmes. 4th ed. Oxford: Oxford University Press; 2015.
Miller WG, Jones GR, Horowitz GL, Weykamp C. Proficiency testing/external quality assessment: current challenges and future directions. Clin Chem. 2011;57(12):1670-1680.
Westgard JO, Westgard SA. The quality of laboratory testing today: an assessment of sigma metrics for analytic quality using performance data from proficiency testing surveys and the CLIA criteria for acceptable performance. Am J Clin Pathol. 2006;125(3):343-354.
Duffy MJ, Lamerz R, Haglund C, et al. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update. Int J Cancer. 2014;134(11):2513-2522.
Locker GY, Hamilton S, Harris J, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24(33):5313-5327.
Charles C, Gafni A, Whelan T. Shared decision-making in the medical encounter: what does it mean? (or it takes at least two to tango). Soc Sci Med. 1997;44(5):681-692.
Barry MJ, Edgman-Levitan S. Shared decision making--pinnacle of patient-centered care. N Engl J Med. 2012;366(9):780-781.
Wan JC, Massie C, Garcia-Corbacho J, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223-238.
Ignatiadis M, Lee M, Jeffrey SS. Circulating tumor cells and circulating tumor DNA: challenges and opportunities on the path to clinical utility. Clin Cancer Res. 2015;21(21):4786-4800.
Tian J, Geng Y, Lv D, et al. Using plasma cell-free DNA to monitor the chemoradiotherapy course of cervical cancer. Int J Cancer. 2019;145(9):2547-2557.
Campitelli M, Jeannot E, Peter M, et al. Human papillomavirus mutational insertion: specific marker of circulating tumor DNA in cervical cancer patients. PLoS One. 2012;7(8):e43393.
Forshew T, Murtaza M, Parkinson C, et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med. 2012;4(136):136ra68.
Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24.
Alix-Panabières C, Pantel K. Liquid biopsy: from discovery to clinical application. Cancer Discov. 2021;11(4):858-873.
Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019;20(2):71-88.
Rajkomar A, Dean J, Kohane I. Machine learning in medicine. N Engl J Med. 2019;380(14):1347-1358.
Topol EJ. High-performance medicine: the convergence of human and artificial intelligence. Nat Med. 2019;25(1):44-56.
Shortliffe EH, Sepúlveda MJ. Clinical decision support in the era of artificial intelligence. JAMA. 2018;320(21):2199-2200.
Sutton RT, Pincock D, Baumgart DC, et al. An overview of clinical decision support systems: benefits, risks, and strategies for success. NPJ Digit Med. 2020;3:17.
Simon R, Roychowdhury S. Implementing personalized cancer genomics in clinical trials. Nat Rev Drug Discov. 2013;12(5):358-369.
Renfro LA, Sargent DJ. Statistical controversies in clinical research: basket trials, umbrella trials, and platform trials: a brief primer and highlights of emerging challenges. Ann Oncol. 2017;28(4):743-747.
Holch JW, Ricard I, Stintzing S, et al. The relevance of baseline circulating tumor DNA analysis for treatment monitoring in metastatic colorectal cancer. PLoS One. 2017;12(3):e0174263.
Tie J, Wang Y, Tomasetti C, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016;8(346):346ra92.
Nimse SB, Sonawane MD, Song KS, Kim T. Biomarker detection technologies and future directions. Analyst. 2016;141(3):740-755.
Pai NP, Vadnais C, Denkinger C, et al. Point-of-care testing for infectious diseases: diversity, complexity, and barriers in developing countries. PLoS Med. 2012;9(9):e1001306.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
