Evaluation of serum level of CA-125 and HE4 in patients with an adnexal mass for the discrimination of benign
from malignant cases
Ahmet Goumlccedilmen Fatih Şanlıkan Yuumlksel Sayın Fatma Seda Oumlztuumlrk Abduumllhamid Guumller
Uumlmraniye Eğitim ve Araştırma Hastanesi
Epidemiology
225000 new incidence annually worldwide Incidence
stable since 1970s
Median age at diagnosis 63
Fifth most common cause of cancer death in women
worldwide
gt60 of women diagnosed with Stage IIIIV
To date no mortality benefit demonstrated with CA125 and
TVUS screening
Ovarian Cancer bull 171 lifetime risk1
bull 5-year survival rates (by year of diagnosis)2
ndash 1990-1992 425 ndash 1993-1995 435 ndash 1996-2003 45
bull Mortality relatively unchanged but statistically significant improvement in 5-year survival rates
1 SEER (Surveillance Epidemiology and End Results) Program Web site httpseercancergovstatfactshtmlovaryhtml Accessed April 22 2007
2 httpseercancergovcsr1975_2004results_mergedsect_21_ovarypdf Accessed April 22 2007
Ca 125 limitations
bull An insufficient sensitivity in early stage OC
(only 23-50 surgical stage I cases)
bull It increases in cases of different physiological and pathological conditions (menses pregnancy endometriosis pleura or peritoneal inflammatory diseases etc)
HE4
bull Human Epididymis-specific protein (HE4- WFDC2)
bull It is expressed in normal ovarian tissue but over expressed in ovarian cancer especially serous and endometrioid histotype
bull It is also expressed in some pulmonary endometrial and breast adenocarcinomas mesotheliomas and less often gastrointestinal renal and transitional cell carcinomas
Material and Methods bull n=63 patients who had adnexal mass on imaging studies and underwent
surgical intervention
bull The exclusion criteriashistory of adnexal surgery for benign disease the diagnosis of pelvic mass during pregnancy ovarian malignancy
bull Serum Ca-125 and HE4 levels were measured on preoperative samples with the upper limit of normal defines as 150 pmolL and 35 UmL respectively for HE4 and CA-125
bull Serum Ca-125 HE4 and ROMA (Risk of Ovarian Malignancy Algorithm) were evaluated for sensitivity specificity positive predictive value (PPV) and negative predictive value (NPV) ROC curves were constructed to determine the sensitivity and specificity of tumor markers at several cut-off points for clinical parameters
Benign n=54 Malign n=9 p
Med (Min-Max) MeanplusmnSD Med (Min-Max) MeanplusmnSD Age 41 (18-77) 428plusmn131 51 (40-60) 508plusmn57 0077
Parity 3 (0-8) 25plusmn26 4 (1-7) 37plusmn19 0198
Body mass index 27 (19-38) 275plusmn49 30 (23-33) 289plusmn36 0402
Histopathology n ()
Endometriosis 18 (333)
Serous cystadenoma 9 (166)
Mucinous cystadenoma 7 (129)
Fibrotecoma 7 (129)
Hemorrhagic cyst 3 (55)
Struma ovari 2 (37)
Mature teratoma 2 (37)
Abscess 2 37)
Others 1 (18)
Histopathology n ()
Serous Papillary carcinoma 6 (666)
Mixed type adenocarcinoma 1 (111)
Mucinous adenocarcinoma 1 (111)
Granulosa cell carcinoma 1 (111)
CA-125 p
Minimum Maximum Mean SD
Bening 93 568 9996 13726
0010 Malign 149 2049 56828 65347
Endometriozis 147 479 14271 14377
Benign Malign Endometriozis ap Min
Max
Mean plusmnSD
MinMax
Mean plusmnSD
Min Max
Mean plusmnSD
HE4 1
368
5454plusmn 5897
64 1317
41862plusmn 45732
2-92 3962plusmn 2491
0001
ROMA 0
77
1182plusmn 1596
14 100
6230plusmn 3718
0-38 866plusmn 1027
0001
n n n bp
Risk Benign 26 703 1 111 13 765
0002 Malign 11 297 8 889 4 235
aKruskall Wallis bFsiher Freeman Halton plt001
Benign Malign p Odds Ratio (95 CI)
Ca125_Grup
0-35 (Normal) 21 389 2 222 0467 22 (04-117)
gt35 33 611 7 778
He-4_Grup
1-150 (Normal) 53 981 5 556 0001 424 (39-4560)
gt150 1 19 4 444
Patology
p Malign Benign Total n n n
CA-125
Malign 7 111 33 534 40 635 0001
Benign 2 32 21 333 23 365
Total 9 143 54 857 63 1000
Sensitivity () 7777
Spesificity () 3889
Positive predictive value 175
Negative predictive value 9130
ODDS 222
n n n p
HE4
Malign 8 127 15 238 23 365 0001
Benign 1 16 39 619 40 635
Toplam 9 143 54 857
Sensitivity () 8888
Spesificity () 7222
Positive predictive value 3478
Negative predictive value 9750
ODDS 208
Pathology p Malign Benign Total
n n n
CA-125+ HE4
Malign 7 778 34 630 22 349 0001
Benign 2 222 20 370 41 651
Total 9 143 54 857 63 1000
Sensitivity () 4444 Spesificity () 99 ODDS 206
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Epidemiology
225000 new incidence annually worldwide Incidence
stable since 1970s
Median age at diagnosis 63
Fifth most common cause of cancer death in women
worldwide
gt60 of women diagnosed with Stage IIIIV
To date no mortality benefit demonstrated with CA125 and
TVUS screening
Ovarian Cancer bull 171 lifetime risk1
bull 5-year survival rates (by year of diagnosis)2
ndash 1990-1992 425 ndash 1993-1995 435 ndash 1996-2003 45
bull Mortality relatively unchanged but statistically significant improvement in 5-year survival rates
1 SEER (Surveillance Epidemiology and End Results) Program Web site httpseercancergovstatfactshtmlovaryhtml Accessed April 22 2007
2 httpseercancergovcsr1975_2004results_mergedsect_21_ovarypdf Accessed April 22 2007
Ca 125 limitations
bull An insufficient sensitivity in early stage OC
(only 23-50 surgical stage I cases)
bull It increases in cases of different physiological and pathological conditions (menses pregnancy endometriosis pleura or peritoneal inflammatory diseases etc)
HE4
bull Human Epididymis-specific protein (HE4- WFDC2)
bull It is expressed in normal ovarian tissue but over expressed in ovarian cancer especially serous and endometrioid histotype
bull It is also expressed in some pulmonary endometrial and breast adenocarcinomas mesotheliomas and less often gastrointestinal renal and transitional cell carcinomas
Material and Methods bull n=63 patients who had adnexal mass on imaging studies and underwent
surgical intervention
bull The exclusion criteriashistory of adnexal surgery for benign disease the diagnosis of pelvic mass during pregnancy ovarian malignancy
bull Serum Ca-125 and HE4 levels were measured on preoperative samples with the upper limit of normal defines as 150 pmolL and 35 UmL respectively for HE4 and CA-125
bull Serum Ca-125 HE4 and ROMA (Risk of Ovarian Malignancy Algorithm) were evaluated for sensitivity specificity positive predictive value (PPV) and negative predictive value (NPV) ROC curves were constructed to determine the sensitivity and specificity of tumor markers at several cut-off points for clinical parameters
Benign n=54 Malign n=9 p
Med (Min-Max) MeanplusmnSD Med (Min-Max) MeanplusmnSD Age 41 (18-77) 428plusmn131 51 (40-60) 508plusmn57 0077
Parity 3 (0-8) 25plusmn26 4 (1-7) 37plusmn19 0198
Body mass index 27 (19-38) 275plusmn49 30 (23-33) 289plusmn36 0402
Histopathology n ()
Endometriosis 18 (333)
Serous cystadenoma 9 (166)
Mucinous cystadenoma 7 (129)
Fibrotecoma 7 (129)
Hemorrhagic cyst 3 (55)
Struma ovari 2 (37)
Mature teratoma 2 (37)
Abscess 2 37)
Others 1 (18)
Histopathology n ()
Serous Papillary carcinoma 6 (666)
Mixed type adenocarcinoma 1 (111)
Mucinous adenocarcinoma 1 (111)
Granulosa cell carcinoma 1 (111)
CA-125 p
Minimum Maximum Mean SD
Bening 93 568 9996 13726
0010 Malign 149 2049 56828 65347
Endometriozis 147 479 14271 14377
Benign Malign Endometriozis ap Min
Max
Mean plusmnSD
MinMax
Mean plusmnSD
Min Max
Mean plusmnSD
HE4 1
368
5454plusmn 5897
64 1317
41862plusmn 45732
2-92 3962plusmn 2491
0001
ROMA 0
77
1182plusmn 1596
14 100
6230plusmn 3718
0-38 866plusmn 1027
0001
n n n bp
Risk Benign 26 703 1 111 13 765
0002 Malign 11 297 8 889 4 235
aKruskall Wallis bFsiher Freeman Halton plt001
Benign Malign p Odds Ratio (95 CI)
Ca125_Grup
0-35 (Normal) 21 389 2 222 0467 22 (04-117)
gt35 33 611 7 778
He-4_Grup
1-150 (Normal) 53 981 5 556 0001 424 (39-4560)
gt150 1 19 4 444
Patology
p Malign Benign Total n n n
CA-125
Malign 7 111 33 534 40 635 0001
Benign 2 32 21 333 23 365
Total 9 143 54 857 63 1000
Sensitivity () 7777
Spesificity () 3889
Positive predictive value 175
Negative predictive value 9130
ODDS 222
n n n p
HE4
Malign 8 127 15 238 23 365 0001
Benign 1 16 39 619 40 635
Toplam 9 143 54 857
Sensitivity () 8888
Spesificity () 7222
Positive predictive value 3478
Negative predictive value 9750
ODDS 208
Pathology p Malign Benign Total
n n n
CA-125+ HE4
Malign 7 778 34 630 22 349 0001
Benign 2 222 20 370 41 651
Total 9 143 54 857 63 1000
Sensitivity () 4444 Spesificity () 99 ODDS 206
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Ovarian Cancer bull 171 lifetime risk1
bull 5-year survival rates (by year of diagnosis)2
ndash 1990-1992 425 ndash 1993-1995 435 ndash 1996-2003 45
bull Mortality relatively unchanged but statistically significant improvement in 5-year survival rates
1 SEER (Surveillance Epidemiology and End Results) Program Web site httpseercancergovstatfactshtmlovaryhtml Accessed April 22 2007
2 httpseercancergovcsr1975_2004results_mergedsect_21_ovarypdf Accessed April 22 2007
Ca 125 limitations
bull An insufficient sensitivity in early stage OC
(only 23-50 surgical stage I cases)
bull It increases in cases of different physiological and pathological conditions (menses pregnancy endometriosis pleura or peritoneal inflammatory diseases etc)
HE4
bull Human Epididymis-specific protein (HE4- WFDC2)
bull It is expressed in normal ovarian tissue but over expressed in ovarian cancer especially serous and endometrioid histotype
bull It is also expressed in some pulmonary endometrial and breast adenocarcinomas mesotheliomas and less often gastrointestinal renal and transitional cell carcinomas
Material and Methods bull n=63 patients who had adnexal mass on imaging studies and underwent
surgical intervention
bull The exclusion criteriashistory of adnexal surgery for benign disease the diagnosis of pelvic mass during pregnancy ovarian malignancy
bull Serum Ca-125 and HE4 levels were measured on preoperative samples with the upper limit of normal defines as 150 pmolL and 35 UmL respectively for HE4 and CA-125
bull Serum Ca-125 HE4 and ROMA (Risk of Ovarian Malignancy Algorithm) were evaluated for sensitivity specificity positive predictive value (PPV) and negative predictive value (NPV) ROC curves were constructed to determine the sensitivity and specificity of tumor markers at several cut-off points for clinical parameters
Benign n=54 Malign n=9 p
Med (Min-Max) MeanplusmnSD Med (Min-Max) MeanplusmnSD Age 41 (18-77) 428plusmn131 51 (40-60) 508plusmn57 0077
Parity 3 (0-8) 25plusmn26 4 (1-7) 37plusmn19 0198
Body mass index 27 (19-38) 275plusmn49 30 (23-33) 289plusmn36 0402
Histopathology n ()
Endometriosis 18 (333)
Serous cystadenoma 9 (166)
Mucinous cystadenoma 7 (129)
Fibrotecoma 7 (129)
Hemorrhagic cyst 3 (55)
Struma ovari 2 (37)
Mature teratoma 2 (37)
Abscess 2 37)
Others 1 (18)
Histopathology n ()
Serous Papillary carcinoma 6 (666)
Mixed type adenocarcinoma 1 (111)
Mucinous adenocarcinoma 1 (111)
Granulosa cell carcinoma 1 (111)
CA-125 p
Minimum Maximum Mean SD
Bening 93 568 9996 13726
0010 Malign 149 2049 56828 65347
Endometriozis 147 479 14271 14377
Benign Malign Endometriozis ap Min
Max
Mean plusmnSD
MinMax
Mean plusmnSD
Min Max
Mean plusmnSD
HE4 1
368
5454plusmn 5897
64 1317
41862plusmn 45732
2-92 3962plusmn 2491
0001
ROMA 0
77
1182plusmn 1596
14 100
6230plusmn 3718
0-38 866plusmn 1027
0001
n n n bp
Risk Benign 26 703 1 111 13 765
0002 Malign 11 297 8 889 4 235
aKruskall Wallis bFsiher Freeman Halton plt001
Benign Malign p Odds Ratio (95 CI)
Ca125_Grup
0-35 (Normal) 21 389 2 222 0467 22 (04-117)
gt35 33 611 7 778
He-4_Grup
1-150 (Normal) 53 981 5 556 0001 424 (39-4560)
gt150 1 19 4 444
Patology
p Malign Benign Total n n n
CA-125
Malign 7 111 33 534 40 635 0001
Benign 2 32 21 333 23 365
Total 9 143 54 857 63 1000
Sensitivity () 7777
Spesificity () 3889
Positive predictive value 175
Negative predictive value 9130
ODDS 222
n n n p
HE4
Malign 8 127 15 238 23 365 0001
Benign 1 16 39 619 40 635
Toplam 9 143 54 857
Sensitivity () 8888
Spesificity () 7222
Positive predictive value 3478
Negative predictive value 9750
ODDS 208
Pathology p Malign Benign Total
n n n
CA-125+ HE4
Malign 7 778 34 630 22 349 0001
Benign 2 222 20 370 41 651
Total 9 143 54 857 63 1000
Sensitivity () 4444 Spesificity () 99 ODDS 206
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Ca 125 limitations
bull An insufficient sensitivity in early stage OC
(only 23-50 surgical stage I cases)
bull It increases in cases of different physiological and pathological conditions (menses pregnancy endometriosis pleura or peritoneal inflammatory diseases etc)
HE4
bull Human Epididymis-specific protein (HE4- WFDC2)
bull It is expressed in normal ovarian tissue but over expressed in ovarian cancer especially serous and endometrioid histotype
bull It is also expressed in some pulmonary endometrial and breast adenocarcinomas mesotheliomas and less often gastrointestinal renal and transitional cell carcinomas
Material and Methods bull n=63 patients who had adnexal mass on imaging studies and underwent
surgical intervention
bull The exclusion criteriashistory of adnexal surgery for benign disease the diagnosis of pelvic mass during pregnancy ovarian malignancy
bull Serum Ca-125 and HE4 levels were measured on preoperative samples with the upper limit of normal defines as 150 pmolL and 35 UmL respectively for HE4 and CA-125
bull Serum Ca-125 HE4 and ROMA (Risk of Ovarian Malignancy Algorithm) were evaluated for sensitivity specificity positive predictive value (PPV) and negative predictive value (NPV) ROC curves were constructed to determine the sensitivity and specificity of tumor markers at several cut-off points for clinical parameters
Benign n=54 Malign n=9 p
Med (Min-Max) MeanplusmnSD Med (Min-Max) MeanplusmnSD Age 41 (18-77) 428plusmn131 51 (40-60) 508plusmn57 0077
Parity 3 (0-8) 25plusmn26 4 (1-7) 37plusmn19 0198
Body mass index 27 (19-38) 275plusmn49 30 (23-33) 289plusmn36 0402
Histopathology n ()
Endometriosis 18 (333)
Serous cystadenoma 9 (166)
Mucinous cystadenoma 7 (129)
Fibrotecoma 7 (129)
Hemorrhagic cyst 3 (55)
Struma ovari 2 (37)
Mature teratoma 2 (37)
Abscess 2 37)
Others 1 (18)
Histopathology n ()
Serous Papillary carcinoma 6 (666)
Mixed type adenocarcinoma 1 (111)
Mucinous adenocarcinoma 1 (111)
Granulosa cell carcinoma 1 (111)
CA-125 p
Minimum Maximum Mean SD
Bening 93 568 9996 13726
0010 Malign 149 2049 56828 65347
Endometriozis 147 479 14271 14377
Benign Malign Endometriozis ap Min
Max
Mean plusmnSD
MinMax
Mean plusmnSD
Min Max
Mean plusmnSD
HE4 1
368
5454plusmn 5897
64 1317
41862plusmn 45732
2-92 3962plusmn 2491
0001
ROMA 0
77
1182plusmn 1596
14 100
6230plusmn 3718
0-38 866plusmn 1027
0001
n n n bp
Risk Benign 26 703 1 111 13 765
0002 Malign 11 297 8 889 4 235
aKruskall Wallis bFsiher Freeman Halton plt001
Benign Malign p Odds Ratio (95 CI)
Ca125_Grup
0-35 (Normal) 21 389 2 222 0467 22 (04-117)
gt35 33 611 7 778
He-4_Grup
1-150 (Normal) 53 981 5 556 0001 424 (39-4560)
gt150 1 19 4 444
Patology
p Malign Benign Total n n n
CA-125
Malign 7 111 33 534 40 635 0001
Benign 2 32 21 333 23 365
Total 9 143 54 857 63 1000
Sensitivity () 7777
Spesificity () 3889
Positive predictive value 175
Negative predictive value 9130
ODDS 222
n n n p
HE4
Malign 8 127 15 238 23 365 0001
Benign 1 16 39 619 40 635
Toplam 9 143 54 857
Sensitivity () 8888
Spesificity () 7222
Positive predictive value 3478
Negative predictive value 9750
ODDS 208
Pathology p Malign Benign Total
n n n
CA-125+ HE4
Malign 7 778 34 630 22 349 0001
Benign 2 222 20 370 41 651
Total 9 143 54 857 63 1000
Sensitivity () 4444 Spesificity () 99 ODDS 206
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
HE4
bull Human Epididymis-specific protein (HE4- WFDC2)
bull It is expressed in normal ovarian tissue but over expressed in ovarian cancer especially serous and endometrioid histotype
bull It is also expressed in some pulmonary endometrial and breast adenocarcinomas mesotheliomas and less often gastrointestinal renal and transitional cell carcinomas
Material and Methods bull n=63 patients who had adnexal mass on imaging studies and underwent
surgical intervention
bull The exclusion criteriashistory of adnexal surgery for benign disease the diagnosis of pelvic mass during pregnancy ovarian malignancy
bull Serum Ca-125 and HE4 levels were measured on preoperative samples with the upper limit of normal defines as 150 pmolL and 35 UmL respectively for HE4 and CA-125
bull Serum Ca-125 HE4 and ROMA (Risk of Ovarian Malignancy Algorithm) were evaluated for sensitivity specificity positive predictive value (PPV) and negative predictive value (NPV) ROC curves were constructed to determine the sensitivity and specificity of tumor markers at several cut-off points for clinical parameters
Benign n=54 Malign n=9 p
Med (Min-Max) MeanplusmnSD Med (Min-Max) MeanplusmnSD Age 41 (18-77) 428plusmn131 51 (40-60) 508plusmn57 0077
Parity 3 (0-8) 25plusmn26 4 (1-7) 37plusmn19 0198
Body mass index 27 (19-38) 275plusmn49 30 (23-33) 289plusmn36 0402
Histopathology n ()
Endometriosis 18 (333)
Serous cystadenoma 9 (166)
Mucinous cystadenoma 7 (129)
Fibrotecoma 7 (129)
Hemorrhagic cyst 3 (55)
Struma ovari 2 (37)
Mature teratoma 2 (37)
Abscess 2 37)
Others 1 (18)
Histopathology n ()
Serous Papillary carcinoma 6 (666)
Mixed type adenocarcinoma 1 (111)
Mucinous adenocarcinoma 1 (111)
Granulosa cell carcinoma 1 (111)
CA-125 p
Minimum Maximum Mean SD
Bening 93 568 9996 13726
0010 Malign 149 2049 56828 65347
Endometriozis 147 479 14271 14377
Benign Malign Endometriozis ap Min
Max
Mean plusmnSD
MinMax
Mean plusmnSD
Min Max
Mean plusmnSD
HE4 1
368
5454plusmn 5897
64 1317
41862plusmn 45732
2-92 3962plusmn 2491
0001
ROMA 0
77
1182plusmn 1596
14 100
6230plusmn 3718
0-38 866plusmn 1027
0001
n n n bp
Risk Benign 26 703 1 111 13 765
0002 Malign 11 297 8 889 4 235
aKruskall Wallis bFsiher Freeman Halton plt001
Benign Malign p Odds Ratio (95 CI)
Ca125_Grup
0-35 (Normal) 21 389 2 222 0467 22 (04-117)
gt35 33 611 7 778
He-4_Grup
1-150 (Normal) 53 981 5 556 0001 424 (39-4560)
gt150 1 19 4 444
Patology
p Malign Benign Total n n n
CA-125
Malign 7 111 33 534 40 635 0001
Benign 2 32 21 333 23 365
Total 9 143 54 857 63 1000
Sensitivity () 7777
Spesificity () 3889
Positive predictive value 175
Negative predictive value 9130
ODDS 222
n n n p
HE4
Malign 8 127 15 238 23 365 0001
Benign 1 16 39 619 40 635
Toplam 9 143 54 857
Sensitivity () 8888
Spesificity () 7222
Positive predictive value 3478
Negative predictive value 9750
ODDS 208
Pathology p Malign Benign Total
n n n
CA-125+ HE4
Malign 7 778 34 630 22 349 0001
Benign 2 222 20 370 41 651
Total 9 143 54 857 63 1000
Sensitivity () 4444 Spesificity () 99 ODDS 206
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Material and Methods bull n=63 patients who had adnexal mass on imaging studies and underwent
surgical intervention
bull The exclusion criteriashistory of adnexal surgery for benign disease the diagnosis of pelvic mass during pregnancy ovarian malignancy
bull Serum Ca-125 and HE4 levels were measured on preoperative samples with the upper limit of normal defines as 150 pmolL and 35 UmL respectively for HE4 and CA-125
bull Serum Ca-125 HE4 and ROMA (Risk of Ovarian Malignancy Algorithm) were evaluated for sensitivity specificity positive predictive value (PPV) and negative predictive value (NPV) ROC curves were constructed to determine the sensitivity and specificity of tumor markers at several cut-off points for clinical parameters
Benign n=54 Malign n=9 p
Med (Min-Max) MeanplusmnSD Med (Min-Max) MeanplusmnSD Age 41 (18-77) 428plusmn131 51 (40-60) 508plusmn57 0077
Parity 3 (0-8) 25plusmn26 4 (1-7) 37plusmn19 0198
Body mass index 27 (19-38) 275plusmn49 30 (23-33) 289plusmn36 0402
Histopathology n ()
Endometriosis 18 (333)
Serous cystadenoma 9 (166)
Mucinous cystadenoma 7 (129)
Fibrotecoma 7 (129)
Hemorrhagic cyst 3 (55)
Struma ovari 2 (37)
Mature teratoma 2 (37)
Abscess 2 37)
Others 1 (18)
Histopathology n ()
Serous Papillary carcinoma 6 (666)
Mixed type adenocarcinoma 1 (111)
Mucinous adenocarcinoma 1 (111)
Granulosa cell carcinoma 1 (111)
CA-125 p
Minimum Maximum Mean SD
Bening 93 568 9996 13726
0010 Malign 149 2049 56828 65347
Endometriozis 147 479 14271 14377
Benign Malign Endometriozis ap Min
Max
Mean plusmnSD
MinMax
Mean plusmnSD
Min Max
Mean plusmnSD
HE4 1
368
5454plusmn 5897
64 1317
41862plusmn 45732
2-92 3962plusmn 2491
0001
ROMA 0
77
1182plusmn 1596
14 100
6230plusmn 3718
0-38 866plusmn 1027
0001
n n n bp
Risk Benign 26 703 1 111 13 765
0002 Malign 11 297 8 889 4 235
aKruskall Wallis bFsiher Freeman Halton plt001
Benign Malign p Odds Ratio (95 CI)
Ca125_Grup
0-35 (Normal) 21 389 2 222 0467 22 (04-117)
gt35 33 611 7 778
He-4_Grup
1-150 (Normal) 53 981 5 556 0001 424 (39-4560)
gt150 1 19 4 444
Patology
p Malign Benign Total n n n
CA-125
Malign 7 111 33 534 40 635 0001
Benign 2 32 21 333 23 365
Total 9 143 54 857 63 1000
Sensitivity () 7777
Spesificity () 3889
Positive predictive value 175
Negative predictive value 9130
ODDS 222
n n n p
HE4
Malign 8 127 15 238 23 365 0001
Benign 1 16 39 619 40 635
Toplam 9 143 54 857
Sensitivity () 8888
Spesificity () 7222
Positive predictive value 3478
Negative predictive value 9750
ODDS 208
Pathology p Malign Benign Total
n n n
CA-125+ HE4
Malign 7 778 34 630 22 349 0001
Benign 2 222 20 370 41 651
Total 9 143 54 857 63 1000
Sensitivity () 4444 Spesificity () 99 ODDS 206
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Benign n=54 Malign n=9 p
Med (Min-Max) MeanplusmnSD Med (Min-Max) MeanplusmnSD Age 41 (18-77) 428plusmn131 51 (40-60) 508plusmn57 0077
Parity 3 (0-8) 25plusmn26 4 (1-7) 37plusmn19 0198
Body mass index 27 (19-38) 275plusmn49 30 (23-33) 289plusmn36 0402
Histopathology n ()
Endometriosis 18 (333)
Serous cystadenoma 9 (166)
Mucinous cystadenoma 7 (129)
Fibrotecoma 7 (129)
Hemorrhagic cyst 3 (55)
Struma ovari 2 (37)
Mature teratoma 2 (37)
Abscess 2 37)
Others 1 (18)
Histopathology n ()
Serous Papillary carcinoma 6 (666)
Mixed type adenocarcinoma 1 (111)
Mucinous adenocarcinoma 1 (111)
Granulosa cell carcinoma 1 (111)
CA-125 p
Minimum Maximum Mean SD
Bening 93 568 9996 13726
0010 Malign 149 2049 56828 65347
Endometriozis 147 479 14271 14377
Benign Malign Endometriozis ap Min
Max
Mean plusmnSD
MinMax
Mean plusmnSD
Min Max
Mean plusmnSD
HE4 1
368
5454plusmn 5897
64 1317
41862plusmn 45732
2-92 3962plusmn 2491
0001
ROMA 0
77
1182plusmn 1596
14 100
6230plusmn 3718
0-38 866plusmn 1027
0001
n n n bp
Risk Benign 26 703 1 111 13 765
0002 Malign 11 297 8 889 4 235
aKruskall Wallis bFsiher Freeman Halton plt001
Benign Malign p Odds Ratio (95 CI)
Ca125_Grup
0-35 (Normal) 21 389 2 222 0467 22 (04-117)
gt35 33 611 7 778
He-4_Grup
1-150 (Normal) 53 981 5 556 0001 424 (39-4560)
gt150 1 19 4 444
Patology
p Malign Benign Total n n n
CA-125
Malign 7 111 33 534 40 635 0001
Benign 2 32 21 333 23 365
Total 9 143 54 857 63 1000
Sensitivity () 7777
Spesificity () 3889
Positive predictive value 175
Negative predictive value 9130
ODDS 222
n n n p
HE4
Malign 8 127 15 238 23 365 0001
Benign 1 16 39 619 40 635
Toplam 9 143 54 857
Sensitivity () 8888
Spesificity () 7222
Positive predictive value 3478
Negative predictive value 9750
ODDS 208
Pathology p Malign Benign Total
n n n
CA-125+ HE4
Malign 7 778 34 630 22 349 0001
Benign 2 222 20 370 41 651
Total 9 143 54 857 63 1000
Sensitivity () 4444 Spesificity () 99 ODDS 206
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
CA-125 p
Minimum Maximum Mean SD
Bening 93 568 9996 13726
0010 Malign 149 2049 56828 65347
Endometriozis 147 479 14271 14377
Benign Malign Endometriozis ap Min
Max
Mean plusmnSD
MinMax
Mean plusmnSD
Min Max
Mean plusmnSD
HE4 1
368
5454plusmn 5897
64 1317
41862plusmn 45732
2-92 3962plusmn 2491
0001
ROMA 0
77
1182plusmn 1596
14 100
6230plusmn 3718
0-38 866plusmn 1027
0001
n n n bp
Risk Benign 26 703 1 111 13 765
0002 Malign 11 297 8 889 4 235
aKruskall Wallis bFsiher Freeman Halton plt001
Benign Malign p Odds Ratio (95 CI)
Ca125_Grup
0-35 (Normal) 21 389 2 222 0467 22 (04-117)
gt35 33 611 7 778
He-4_Grup
1-150 (Normal) 53 981 5 556 0001 424 (39-4560)
gt150 1 19 4 444
Patology
p Malign Benign Total n n n
CA-125
Malign 7 111 33 534 40 635 0001
Benign 2 32 21 333 23 365
Total 9 143 54 857 63 1000
Sensitivity () 7777
Spesificity () 3889
Positive predictive value 175
Negative predictive value 9130
ODDS 222
n n n p
HE4
Malign 8 127 15 238 23 365 0001
Benign 1 16 39 619 40 635
Toplam 9 143 54 857
Sensitivity () 8888
Spesificity () 7222
Positive predictive value 3478
Negative predictive value 9750
ODDS 208
Pathology p Malign Benign Total
n n n
CA-125+ HE4
Malign 7 778 34 630 22 349 0001
Benign 2 222 20 370 41 651
Total 9 143 54 857 63 1000
Sensitivity () 4444 Spesificity () 99 ODDS 206
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Benign Malign p Odds Ratio (95 CI)
Ca125_Grup
0-35 (Normal) 21 389 2 222 0467 22 (04-117)
gt35 33 611 7 778
He-4_Grup
1-150 (Normal) 53 981 5 556 0001 424 (39-4560)
gt150 1 19 4 444
Patology
p Malign Benign Total n n n
CA-125
Malign 7 111 33 534 40 635 0001
Benign 2 32 21 333 23 365
Total 9 143 54 857 63 1000
Sensitivity () 7777
Spesificity () 3889
Positive predictive value 175
Negative predictive value 9130
ODDS 222
n n n p
HE4
Malign 8 127 15 238 23 365 0001
Benign 1 16 39 619 40 635
Toplam 9 143 54 857
Sensitivity () 8888
Spesificity () 7222
Positive predictive value 3478
Negative predictive value 9750
ODDS 208
Pathology p Malign Benign Total
n n n
CA-125+ HE4
Malign 7 778 34 630 22 349 0001
Benign 2 222 20 370 41 651
Total 9 143 54 857 63 1000
Sensitivity () 4444 Spesificity () 99 ODDS 206
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Patology
p Malign Benign Total n n n
CA-125
Malign 7 111 33 534 40 635 0001
Benign 2 32 21 333 23 365
Total 9 143 54 857 63 1000
Sensitivity () 7777
Spesificity () 3889
Positive predictive value 175
Negative predictive value 9130
ODDS 222
n n n p
HE4
Malign 8 127 15 238 23 365 0001
Benign 1 16 39 619 40 635
Toplam 9 143 54 857
Sensitivity () 8888
Spesificity () 7222
Positive predictive value 3478
Negative predictive value 9750
ODDS 208
Pathology p Malign Benign Total
n n n
CA-125+ HE4
Malign 7 778 34 630 22 349 0001
Benign 2 222 20 370 41 651
Total 9 143 54 857 63 1000
Sensitivity () 4444 Spesificity () 99 ODDS 206
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Pathology p Malign Benign Total
n n n
CA-125+ HE4
Malign 7 778 34 630 22 349 0001
Benign 2 222 20 370 41 651
Total 9 143 54 857 63 1000
Sensitivity () 4444 Spesificity () 99 ODDS 206
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Cut-off values for Ca-125 and HE4 were set at 152 UmL and 655 pmolL with 761 and 917 diagnostic accuracy respectively
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Karlsen MAGynecol Oncol 2012 n=1218
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Comparison of HE4 CA125 and ROMA algorithm in women with a pelvic mass Correlation with pathological outcome
Sandri MT1Gynecol Oncol 2013
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
N= 7792 tests (11 studies) ROMA for EOC sensitivity 89 specificity 83 and AUC 93 Comparison of EOC predictive value specificity HE4 (93) gt CA125 (84) AUC CA125 88 gt HE4 82 Comparison of OC predictive value AUC CA125 (89) gt HE4 (79) Comparison among the three tests for EOC prediction sensitivity ROMA (86) gtHE4 (80) specificity HE4 (95) gt ROMA (84) gt CA125 (78)
Li2012
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
n= 6269 (31 trials) bull HE4 Sensitivity 73 (95 CI 071ndash075)
Specificity 89 (95 CI 088ndash090)
Positive likelihood ratio 730 (95 CI 542ndash984)
Negative likelihood ratio 015 (95 CI 010ndash023)
Yang et al2013
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers
Conclusion
bull The combination of CA-125 and HE4 may improve the diagnostic accuracy for the discrimination of benign adnexal mass from malignant cases
bull Further studies into the molecular basis of tumor biology might contribute the current understanding of the nature of the ovarian cancer and tumor markers