Article Information

Dr. Moushume Akther Liza¹*, Dr. Rowson Ara², Dr. Sunzia Sayed³, Dr. Asma Akter Sonia⁴, Dr. Jannatul Islam⁵, Dr. Tahsin Zaman⁶, Dr. Shabnom Mostofa Purobi⁷

¹Resident, Department of Gynaecological Oncology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

²Assistant Professor, Department of Obstetrics and Gynecology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

³Resident, Department of Gynaecological Oncology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

⁴Assistant professor, Department of Obstetrics and Gynecology, Khwaja Yunus Ali Medical College & Hospital, Sirajganj, Bangladesh.

⁵Medical officer, Upazila Health Complex, Daudcandi, Cumilla, Bangladesh.

⁶Junior Consultant, Directorate General of Health Services (DGHS), Mohakhali, Dhaka, Bangladesh

⁷Resident, Department of Gynaecological Oncology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.

*Corresponding author: Dr. Moushume Akther Liza, Resident, Department of Gynaecological Oncology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Received: 28 October 2024; Accepted: 04 November 2024; Published: 05 November 2024

Citation: Dr. Moushume Akther Liza, Dr. Rowson Ara, Dr. Sunzia Sayed, Dr. Asma Akter Sonia, Dr. Jannatul Islam, Dr. Tahsin Zaman, Dr. Shabnom Mostofa Purobi. Relationship Between Albumin to Fibrinogen Ratio and Different Stages of Cervical Cancer in a Tertiary Care Center. Obstetrics and Gynecology Research. 7 (2024): 110-115.

Abstract

Keywords

Cervical cancer; Albumin-to-fibrinogen ratio; Staging; Prognosis; Tertiary care center

Article Details

Introduction:

Cervical cancer is a significant global health concern, being the fourth most common cancer diagnosed and the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020 [1]. In Bangladesh, the GLOBOCAN 2020 database reports crude incidence and mortality rates for cervical cancer are 10.2 and 6.1 per 100,000, respectively  [2]. Alarmingly, 84% of new cases and between 87 and 90% of deaths occur in low- and middle-income countries [3] underscoring the critical need for studies assessing the relationship between pretreatment factors, such as the albumin-to-fibrinogen ratio (AFR), and the stages of cervical cancer.

The high incidence of cervical cancer in developing countries is due to the ineffectiveness of a comprehensive population-based early detection of cervical precancerous lesions, along with low awareness, education levels, and public knowledge about the occurrence of this cancer [4]. In 2020, Southeast Asia was ranked seventh for cervical cancer incidence and sixth for mortality compared to other regions of the world [5].

The International Federation of Gynecology and Obstetrics (FIGO) classification system is widely used for staging cervical cancer, based on clinical examination of the anatomical extent of the disease. In 2018, the FIGO cancer committee modified the staging to incorporate imaging findings for tumor size measurement and evaluation of lymph node metastasis [6].

Inflammation is a hallmark of cancer and contributes to various aspects of tumor progression, including angiogenesis, immune evasion, and metastasis. Consequently, systemic inflammatory markers have gained attention as potential prognostic indicators in cancer patients [7]. Low serum albumin levels are often observed in cancer patients and are associated with poor outcomes due to factors such as malnutrition, inflammation, and cancer-induced alterations in protein metabolism [8,9].

Fibrinogen, on the other hand, is a glycoprotein involved in blood clotting and wound healing. Elevated fibrinogen levels have been associated with a pro-inflammatory state and linked to cancer progression and metastasis [10]. The prognosis and survival rates of cervical cancer are closely related to the stage at which the disease is diagnosed [11]. Five-year survival rates range from over 90% if diagnosed at an early, localized stage to less than 20% if diagnosed as distant or metastatic [12] Early-stage cervical cancer typically includes stages IA, IB, and IIA, while advanced cervical cancer includes stages IIB, III, and IVA and IVB [13].

The albumin-to-fibrinogen ratio (AFR) combines two markers, offering insights into the balance between the body's immune response and the acute-phase reaction during cancer. The diagnostic efficacy of the albumin-to-fibrinogen ratio has been exhibited in several types of human cancers [14,15]. but the role of AFR in predicting stages of cervical cancer remains a topic of conflicting findings within the existing literature. Therefore, the purpose of this study was to determine the relationship of albumin-to-fibrinogen ratio in different stages of cervical cancer.

Objectives

• • The aim of the study was to assess the relationship between pretreatment albumin-to-fibrinogen ratio (AFR) and the stages of cervical cancer in a tertiary care center.

Methodology & Materials

This cross-sectional analytical study was conducted at the Department of Gynecological Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, between July 2022 and June 2023, focusing on women with biopsy-confirmed cervical cancer. A total of 70 participants were recruited, divided into two groups: early-stage (IA-IIA) and advanced-stage (IIB-IV).

Inclusion Criteria:

• • Women diagnosed with cervical cancer confirmed by histopathology report obtained from biopsy.
• • Had given consent to participate in the study.

Exclusion Criteria:

• • Women with a history of previous surgery, chemotherapy, or radiation treatment for cervical disease or neoplasia.
• • Women with known HIV infection.
• • • Women with known hematological diseases, autoimmune diseases, infectious diseases, or concomitant malignant tumors.
• • Women with any other cancer.
• • Women receiving any anticoagulant drugs before enrollment.

Informed consent was obtained from all participants, ensuring confidentiality and voluntary participation. A thorough medical history and clinical examinations were conducted. Staging of cervical cancer was performed based on FIGO 2018 classifications, categorizing the stages into early stage (IA-IIA) and advanced stage (IIB-IV). Serum albumin and fibrinogen levels were measured to calculate the albumin to fibrinogen ratio (AFR), an inflammatory index. Data were collected using a pre-designed semi-structured questionnaire capturing socio-demographic details, clinical variables (age at first sexual intercourse, age at first childbirth, parity, BMI, and history of oral contraceptive use), and laboratory results. Analyses were performed using SPSS version 27.0, with continuous variables presented as means with standard deviations and categorical variables as counts with percentages. Comparisons between early-stage and advanced-stage cervical cancer groups used t-tests or chi-square tests, with a significance level set at p < 0.05. Univariate and multivariate logistic regression models assessed associations while adjusting for potential confounding variables. The study was approved by the Institutional Review Board (IRB) of Bangabandhu Sheikh Mujib Medical University (BSMMU), ensuring compliance with ethical guidelines and patient confidentiality. The primary outcome variables included the relationship between cervical cancer stages and various demographic and clinical factors in women diagnosed with cervical cancer.

Result

Table 1: Distribution of respondents according to their socio-demographic characteristics (n=70).

Table 1 shows that 47.1% of the patients were within the 30-44 years age group, and the average age was 45.37 ± 9.54 years. A total of 68.6% were educated up to the primary level, 85.7% were married, 84.3% were housewives, and 64.3% belonged to the lower-middle-class social status, with a monthly family income between 7,379 and 28,810 Tk.

Figure 1: Bar diagram showing the distribution of respondents according to clinical staging (FIGO stages) of cervical cancer (n=70)

Figure 1 depicts the distribution of study subjects across different stages of cervical cancer. Out of 70 subjects, 31 (44.3%) were in FIGO stage I (IA1 4.29%, IA2 5.71%, IB1 8.57%, IB2 21.43%, and IB3 4.29%), 17 (24.3%) in stage II (IIA1 4.29%, IIA2 1.43%, and IIB 18.57%), 19 (27.1%) in stage III (IIIA 7.1%, IIIB 15.7%, IIIC1 2.9%, and IIIC2 1.4%), and 3 (4.3%) in stage IV (IVA 4.29%).

Figure 2: Pie diagram showing the distribution of respondents in advanced and early stages of cervical cancer (n=70)

Figure 2 shows that 35 (50.0%) of the respondents had advanced-stage cervical cancer, while the remaining 35 (50.0%) were identified at an early stage.

Figure 3: Histogram showing the distribution of pretreatment AFR among respondents with cervical cancer

Figure 3 illustrates the distribution of the pretreatment albumin-to-fibrinogen ratio (AFR) among the respondents with cervical cancer. The overall mean AFR was 10.26 ± 1.47, with a median value of 10.23.

Table 2: Comparison of respondents' albumin-to-fibrinogen ratio across different stages of cervical cancer (n=70).

Table 2 shows no statistically significant difference in AFR between stage I and stage II cervical cancer (p > 0.05). However, significant differences were observed between stage I and stage III (p = 0.012), stage I and stage IV (p = 0.023), stage II and stage III (p = 0.02), stage II and stage IV (p = 0.013), and stage III and stage IV (p = 0.046).

Figure 4: Scatterplot showing the correlation between pretreatment AFR and stages of cervical cancer (rs = -0.421, p < 0.001)

Figure 4 demonstrates the correlation between the pretreatment albumin-to-fibrinogen ratio and the clinical stages of cervical cancer. A significant negative correlation was observed (rs = -0.421, p < 0.001).

Table 3: Odds ratios (OR) and 95% confidence intervals (CI) for stages based on pretreatment AFR in cervical cancer patients (Group A = 35, Group B = 35).

Table 3 reveals a significant difference in pretreatment AFR between advanced and early-stage cervical cancer groups (p < 0.001). Respondents with an AFR < 10.7 had a 10.2-fold higher chance of developing advanced-stage cervical cancer compared to those with an AFR ≥ 10.7 (OR = 10.154; 95% CI = 3.155-32.681).

Discussion

Cervical cancer is a significant health concern in Bangladesh, with high incidence rates primarily due to limited access to screening and healthcare services, emphasizing the need for improved awareness and prevention efforts. Early detection through proper staging is crucial for effective treatment and positive patient outcomes. The albumin-to-fibrinogen ratio (AFR) reflects inflammatory and nutritional status as well as coagulation function, which can aid in assessing the severity of cervical cancer. In this cross-sectional study, a total of 70 histopathologically diagnosed women with cervical cancer were consecutively included and evaluated for their AFR and clinical stages. Respondents with advanced-stage cancer (stage IIB-IV) were categorized into group A (n=35), while those with early-stage cancer (stage IA-IIA) were categorized into group B (n=35).

In the present study, 47.1% of the patients were within the 30-44 years age group, and in the advanced cervical cancer group, the mean age was slightly higher at 46.93±10.62 years compared to the early-stage group at 43.91±8.22 years (p=0.203). Nearly two-thirds (68.6%) of the participants were educated up to the primary level. The majority (85.7%) were married, 84.3% were housewives, and 64.3% belonged to the lower middle-class social status, with a monthly family income ranging from 7,379 to 28,810 Tk. In a similar study by Khanam et al. (2018), comparable findings were reported, with 96.3% of respondents being housewives, 0.2% laborers, 2.3% in service, 0.6% business owners, and 0.6% teachers. They also reported that two-thirds of the families belonged to low- and middle-class income groups [16].

Among women with cervical cancer, 42.9% of those in the advanced group and 51.4% in the early-stage group reported using oral contraceptive pills (OCPs) for contraception. Notably, a substantial proportion in both groups had a history of using OCPs for five or more years (group A: 80.0% vs. group B: 72.2%), with a p-value of 0.699, indicating no statistically significant difference in the duration of OCP use between the two groups. Song et al. (2017) revealed that the average age at menarche was 16.2±1.8 years, and the average age for sexual debut was 21.1±2.1 years. The vast majority (92.0%) of the women employed contraception measures, and 79.7% of them had undergone sterilization [17].

In this study, over a quarter (25.7%) of the overweight women developed advanced cervical cancer compared to 14.3% of women with early-stage cervical cancer. The average body mass index (BMI) of the women was higher in group A compared to group B (22.98±2.44 vs. 21.94±2.19 kg/m²). None of these differences were statistically significant (p>0.05). In a study by Lee et al.18, compared to women with a normal BMI (18.5-23 kg/m²), the odds ratios (ORs) for cervical cancer were 1.25 for overweight (23-25 kg/m²) and 1.70 for mild obesity (≥25 kg/m²), suggesting that obesity may increase cervical cancer risk [18]. This disparity was likely due to the difference in the comparison group.

In the present study, there were notable differences in the mean (±SD) of the albumin-to-fibrinogen ratio (AFR) among different stages of cervical cancer (p<0.05). Stage IV cancer exhibited the lowest mean AFR of 8.41±0.33, while stage I had the highest mean AFR at 10.69±1.63. Furthermore, the average AFR was significantly lower among respondents in group A compared to group B (9.77±1.21 vs. 10.74±1.54; p=0.005). The correlation analysis in this study revealed a statistically significant negative correlation between pretreatment AFR and the stages of cervical cancer, with a Spearman correlation coefficient (rs) of -0.421 and a p-value of less than 0.001. This negative correlation implies that as AFR decreases, the stage of cervical cancer increases. In other words, lower AFR values are associated with more advanced stages of the disease. Respondents with an AFR <10.7 were found to have a 10.2 times higher risk of developing advanced-stage cervical cancer compared to patients with an AFR value ≥10.7 (OR=10.154; 95% CI=3.155-32.681).

Sun et al [19]. assessed the correlation of AFR with cancer prognosis. Pooled univariate and multivariate analyses indicated significant correlations of low AFR with poor overall survival (HR 2.18, 95% CI 1.87-2.55 and HR 1.75, 95% CI 1.54-2.00, respectively), poor disease-free survival (HR 1.89, 95% CI 1.54-2.32 and HR 1.51, 95% CI 1.29-1.76, respectively), and poor progression-free survival (HR 1.68, 95% CI 1.42-1.99 and HR 1.48, 95% CI 1.16-1.88, respectively). They recommended that AFR might be a promising prognostic marker for cancers [19].

Therefore, proper staging is vital for effective treatment and patient outcomes. The albumin-to-fibrinogen ratio (AFR) emerges as a promising prognostic marker, demonstrating a significant negative correlation with disease stage. Moreover, AFR's ability to differentiate between advanced and early-stage cases could aid in clinical decision-making.

Limitations of the study

This study had some limitations:

• • The study was conducted in a selected tertiary-level hospital.
• • The sample was not randomly selected.
• • The sample size was inadequate.

Therefore, the findings of this study cannot be generalized to the entire population.

Conclusion

The relationship between the albumin-to-fibrinogen ratio (AFR) and different stages of cervical cancer, the results indicate that AFR decreases significantly with advancing stages. A mean AFR of 10.26 ± 1.47 was observed overall, with significant differences between later stages (III and IV) compared to early stages (I and II). A negative correlation (rs = -0.421, p < 0.001) was found between AFR and cancer stage. Patients with AFR <10.7 were 10.2 times more likely to present with advanced-stage cervical cancer, demonstrating the potential of AFR as a predictive biomarker for disease progression.

References

1. 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: a cancer journal for clinicians 71 (2021): 209-249.
2. Uddin AK, Sumon MA, Pervin S, et al. Cervical cancer in Bangladesh. South Asian Journal of Cancer. 2023 Jan;12(01):036-038.
3. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer 136 (2015): E359-386.
4. Agustiansyah P, Sanif R, Nurmaini S. Epidemiology and risk factors for cervical cancer. Bioscientia Medicina: Journal of Biomedicine and Translational Research 5 (2021): 624-631.
5. Chua B, Ma V, Asjes C, et al. Barriers to and facilitators of cervical cancer screening among women in Southeast Asia: a systematic review. International journal of environmental research and public health 18 (2021): 4586.
6. Kido A, Nakamoto Y. Implications of the new FIGO staging and the role of imaging in cervical cancer. The British Journal of Radiology 94 (2021): 20201342.
7. Huang L, Mo Z, Zhang L, et al. Diagnostic value of albumin to fibrinogen ratio in cervical Cancer. The International Journal of Biological Markers 35 (2020): 66-73.
8. Belinskaia DA, Voronina PA, Shmurak VI, et al. Serum albumin in health and disease: esterase, antioxidant, transporting and signaling properties. International journal of molecular sciences 22 (2021): 10318.
9. Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutrition journal 9 (2010): 1-6.
10. Dai T, Peng L, Lin G, et al. Preoperative elevated plasma fibrinogen level predicts tumor recurrence and poor prognosis in patients with hepatocellular carcinoma. Journal of Gastrointestinal Oncology 10 (2019): 1049.
11. SP S, KR A. Management of early stage cervical cancer. Reviews on Recent Clinical Trials 10 (2015): 302-308.
12. Ferrall L, Lin KY, Roden RB, Hung CF, Wu TC. Cervical cancer immunotherapy: facts and hopes. Clinical Cancer Research 27 (2021): 4953-4973.
13. Datta NR, Stutz E, Liu M, et al. Concurrent chemoradiotherapy vs. radiotherapy alone in locally advanced cervix cancer: a systematic review and meta-analysis. Gynecologic oncology 145 (2017): 374-385.
14. Li B, Deng H, Lei B, et al. The prognostic value of fibrinogen to albumin ratio in malignant tumor patients: a meta-analysis. Frontiers in Oncology 12 (2022): 985377.
15. Zhang Y, Xiao G. Prognostic significance of the ratio of fibrinogen and albumin in human malignancies: a meta-analysis. Cancer Management and Research 23 (2019): 3381-3393.
16. Khanam A, Jesmin ZF, Begum F, et al. Prevalence of Cervical Intraepithelial Neoplasia (CIN) at Khulna Division of Bangladesh. Bangladesh Journal of Obstetrics & Gynaecology 33 (2018): 21-28.
17. Song Y, Zhao YQ, Li L, et al. A retrospective analysis of the utility of endocervical curettage in screening population. Oncotarget 8 (2017): 50141.
18. Lee JK, So KA, Piyathilake CJ, et al. Mild obesity, physical activity, calorie intake, and the risks of cervical intraepithelial neoplasia and cervical cancer. PloS one 8 (2013): e66555.
19. Sun DW, An L, Lv GY. Albumin-fibrinogen ratio and fibrinogen-prealbumin ratio as promising prognostic markers for cancers: an updated meta-analysis. World journal of surgical oncology 18 (2020): 1-5.