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EVALUATING CA-125 FOR OVARIAN CANCER DETECTION: A REVIEW OF
DIAGNOSTIC PERFORMANCE
Kalash Dwivedi , Sharipov Akramxon Rustamxon ugli¸ Ramseela S, Powrnamy P ,
Aakriti Mandal , Dilshad Waqar, Syed Meyar Husain, Vinayak Koli, Rahmonova U.T.,
Tushar, Jainil Sejpal.
Students of Tashkent Medical Academy, Tashkent Uzbekistan.
Abstract:
Background: Ovarian cancer remains one of the deadliest gynaecologic
malignancies due to its late-stage diagnosis and the lack of effective early screening methods.
CA-125, a serum biomarker, has long been used in clinical practice, but its diagnostic
accuracy continues to be debated.
Objective:
This review aims to evaluate the diagnostic
performance of CA-125 in detecting ovarian cancer across different clinical settings, with
attention to variations based on age, ethnicity, and care context.
Methods:
A structured
literature review was conducted using PubMed, Scopus, and Google Scholar, covering
studies published between 1988 and 2025. From an initial pool of 12 studies, 6 were
included based on relevance, methodological rigor, and availability of quantitative
diagnostic data. Metrics such as sensitivity, specificity, PPV, NPV, and AUC were extracted
and compared.
Results:
CA-125 demonstrated variable diagnostic performance. Sensitivity
ranged from 50% to over 90%, while specificity was generally higher in hospital-based
settings. One Indonesian study reported an overall accuracy of 94.5% using a 36.5 U/ml
cutoff. Ethnicity affected CA-125’s predictive value, with lower PPVs observed in Asian
and Black women. Longitudinal evidence showed that elevated CA-125 levels can precede
clinical diagnosis by several years. However, algorithmic models like ROMA showed only
marginal improvement over CA-125 alone.
Conclusion:
While CA-125 is a useful
diagnostic tool—especially in secondary care—its limitations in primary care and across
diverse populations highlight the need for context-specific interpretation. Integration with
imaging, risk algorithms, and emerging biomarkers may enhance early detection and reduce
false positives in ovarian cancer diagnostics.
Keywords:
Ovarian cancer, CA-125, tumor marker, diagnostic accuracy, sensitivity,
specificity, primary care.
Introduction:-
Ovarian cancer remains a major global health challenge and is currently the
seventh most commonly diagnosed cancer and the eighth leading cause of cancer-related
deaths among women (World Health Organization [WHO], 2023). It is often diagnosed at an
advanced stage due to the asymptomatic nature of early disease and the lack of effective,
widely applicable screening tools, resulting in a poor prognosis for many women (Reid et al.,
2021). The five-year survival rate drops dramatically from over 90% for stage I to less than
30% for stage III or IV disease (Siegel et al., 2023).Among the biomarkers studied for the
early detection of ovarian cancer, cancer antigen 125 (CA-125) remains one of the most
widely used and investigated. First introduced by Bast et al. (1983), CA-125 is a high-
molecular-weight glycoprotein expressed by coelomic epithelial tissues including the
endometrium, fallopian tubes, and peritoneum. Elevated CA-125 levels are present in
approximately 80% of women with advanced epithelial ovarian cancer, but its sensitivity in
early-stage disease is significantly lower—often below 50% (Zurawski et al., 1988; Jacobs
et al., 1996). Furthermore, the biomarker lacks specificity due to its elevation in numerous
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benign conditions such as endometriosis, menstruation, pelvic inflammatory disease, and
even non-gynecologic disorders like liver disease (Funston et al., 2020; Van Gorp et al.,
2011). Despite these limitations, CA-125 continues to be a cornerstone in the clinical
evaluation of women with pelvic masses or symptoms suggestive of ovarian malignancy. In
the United Kingdom, NICE guidelines recommend CA-125 as a first-line test in primary
care, particularly for women presenting with persistent bloating, pelvic pain, or other non-
specific symptoms (Barlow et al., 2025). In secondary care, CA-125 is used in risk
assessment models, such as the Risk of Malignancy Index (RMI) and the Risk of Ovarian
Malignancy Algorithm (ROMA), often combined with ultrasound findings and menopausal
status to stratify cancer risk (Van Gorp et al., 2011). In recent years, researchers have
examined how factors like age, menopausal status, and ethnicity influence CA-125’s
diagnostic accuracy. For instance, Funston et al. (2020) demonstrated that age-adjusted CA-
125 thresholds could more accurately estimate cancer risk, while Barlow et al. (2025)
reported that predictive values were lower among Asian and Black women compared to their
White counterparts, raising concerns about equity in diagnostic evaluation. Given the
variability in CA-125 performance across different settings and populations, there remains
significant debate regarding its optimal clinical application, particularly in low-prevalence
contexts such as primary care. This review aims to systematically assess the diagnostic
accuracy of CA-125 across diverse populations and care settings, with the goal of informing
more precise, equitable, and evidence-based decision-making in ovarian cancer diagnosis.
Methodology:-
This review was conducted to systematically assess the diagnostic accuracy
of serum CA-125 testing for ovarian cancer detection. A comprehensive literature search
was performed across databases including PubMed, Scopus, and Google Scholar to identify
relevant studies published between 1988 and 2025. The search strategy included
combinations of the following keywords: “CA-125,” “ovarian cancer,” “tumor marker,”
“diagnostic accuracy,” “sensitivity,” “specificity,” and “screening.” Articles were screened
by title and abstract, followed by full-text review based on predefined inclusion and
exclusion criteria. Studies were included if they reported quantitative diagnostic metrics of
CA-125 (sensitivity, specificity, PPV, NPV, AUC) in relation to histologically confirmed
ovarian cancer, involved human female subjects aged 18 years and older, and assessed CA-
125 either in primary care, hospital-based settings, or screening populations. Excluded were
reviews, editorials, case reports, and studies not focused on diagnostic performance, such as
those limited to monitoring treatment or prognosis. From an initial pool of 12 eligible
studies, 6 were selected for final inclusion based on methodological quality, completeness of
diagnostic data, and relevance to clinical diagnostic settings. These studies were conducted
across various countries—including the United Kingdom, Indonesia, and Norway—and
encompassed a broad range of clinical scenarios, from symptomatic patients in primary care
to women undergoing surgery for adnexal masses. Sample sizes ranged from 428 to over
200,000 women. For each study, data on setting, sample size, CA-125 cut-off thresholds,
diagnostic performance metrics, and key findings were extracted and tabulated for
comparison. Due to heterogeneity in design and outcomes, no meta-analysis was performed.
The final synthesis aimed to highlight patterns and clinical implications in the use of CA-
125 across diverse patient populations.
Results
:-The diagnostic performance of CA-125 varied across clinical settings and
populations. In a tertiary Indonesian hospital setting, Pangaribuan et al. (2025) found that a
CA-125 cutoff of 36.5 U/ml yielded sensitivity of 86.1%, specificity of 90.1%, and an
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overall diagnostic accuracy of 94.5%, making it a reliable screening tool in patients with
suspected malignancy. In contrast, Barlow et al. (2025), using English primary care data,
observed that ethnic variations significantly influenced CA-125 performance. White women
exhibited higher CA-125 predictive values compared to Asian or Black women. Although
these differences were mitigated after adjusting for age and comorbidities, the authors
advised against ethnicity-specific thresholds due to a risk of reduced sensitivity.In a
landmark prospective study, Jacobs et al. (1996) reported that CA-125 levels ≥30 U/ml
increased the relative risk of ovarian or fallopian tube cancer by 35.9 times within one year,
and levels ≥100 U/ml increased it by over 200-fold, confirming CA-125's value in long-term
risk prediction.Funston et al. (2020), analyzing over 50,000 women in UK primary care,
found that a CA-125 level of 53 U/ml corresponded to a 3% probability of ovarian cancer —
the threshold for urgent investigation in NICE guidelines. However, the PPV varied
significantly with age, from 3.4% in women <50 years to 15.2% in those ≥50 years.
Zurawski et al. (1988) showed that elevated CA-125 could precede diagnosis by up to 60
months, with 50% of pre-diagnostic samples (18 months prior) showing levels >30 U/ml.
Finally, Van Gorp et al. (2011) evaluated the ROMA algorithm, combining CA-125 with
HE4, and found no significant performance gain over CA-125 alone, especially in
postmenopausal women (AUC: CA-125 = 0.877, ROMA = 0.898).
Table 1: Summary of Diagnostic Performance of CA-125 Across Studies
Study
Sampl
e Size
Cutof
f
(U/ml
)
Sensitivi
ty (%)
Specificit
y (%)
PPV
(%)
NPV
(%)
AUC
Key
Findings
Pangaribu
an et al.
(2025)
Not
specifi
ed
36.5
86.1
90.1
89.4 86.9
–
High
diagnostic
accuracy
(94.5%) in
hospital
setting
Barlow et
al. (2025)
200k+
Varie
s
Ethnic
differenc
es
Lower
specificit
y
in
Asian/Bla
ck
women
Vari
es
–
–
No
ethnicity-
specific
cutoffs
recommend
ed
Jacobs et
al. (1996)
22,000 ≥30 /
≥100
RR
↑
35.9x /
204.8x
–
–
0.001
2
(<30
U/ml
)
–
High
predictive
power for
future
cancer
Funston
et
al.
(2020)
50,780 35 /
53 /
Age-
based
3% risk
at
53
U/ml
–
3.4%
(<50
yrs),
15.2
%
(≥50
–
–
Risk
thresholds
useful for
triage
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yrs)
Zurawski
et
al.
(1988)
428
30 /
65
50% >30
U/ml (18
mo
before
Dx)
93% (<30
U/ml in
controls)
~25
%
(>30
U/ml
)
–
–
Detectable
elevations
long before
diagnosis
Van Gorp
et
al.
(2011)
389
ROM
A
67.5
(pre-M),
90.8
(post-M)
87.9 (pre-
M), 66.3
(post-M)
–
–
0.898
(ROM
A),
0.877
(CA-
125)
HE4 adds
limited
value over
CA-125
Detectable elevations long before diagnosis Van Gorp et al. (2011) 389 ROMA 67.5 (pre-M),
90.8 (post-M) 87.9 (pre-M), 66.3 (post-M) – – 0.898 (ROMA), 0.877 (CA-125) HE4 adds
limited value over CA-125
Discussion:-The findings affirm that CA-125 is a clinically useful tool in detecting ovarian
cancer, especially when used in conjunction with patient demographics and clinical
presentation. Its performance is strongest in secondary care and postmenopausal populations,
where specificity and PPV are notably higher. However, in primary care or screening
contexts, the test's low PPV (<5%) in younger women limits its standalone use, necessitating
follow-up imaging or repeat testing. The test’s sensitivity increases with advancing disease,
and its levels may remain normal in early-stage cancers or benign conditions like
endometriosis, liver disease, and menstruation. Age-adjusted and algorithm-based models
like ROMA can offer incremental improvement but have not consistently outperformed CA-
125 alone. Ethnic disparities in test performance highlight the importance of equity in
diagnostic thresholds, though implementing ethnicity-specific cutoffs may compromise
sensitivity. Longitudinal studies also suggest CA-125 may serve as a risk indicator years
before diagnosis, particularly in asymptomatic women.
Conclusion
:-CA-125 continues to serve as a valuable diagnostic and risk stratification tool
for ovarian cancer, with high sensitivity and specificity in tertiary care settings. However, its
limitations in general populations, variability by age and ethnicity, and overlap with benign
conditions mean it should be interpreted cautiously. Clinical decisions should integrate CA-
125 levels with imaging, risk models, and patient context to improve early detection without
increasing false positives. Future research should focus on combinatory biomarkers and
artificial intelligence–driven risk models to optimize the early detection of ovarian cancer.
Acknowledgment
All authors contributed to the development of this article. We especially acknowledge
Kalash Dwivedi
for his valuable input and support throughout the preparation of this review.
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