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Research Article | DOI: https://doi.org/10.31579/2693-4787/036
1 Department of Zoology, Faculty of Science, Zawia University, Libya.
2 Department of Physiology, Faculty of Medicine, Sabratha University, Libya.
3 Department of Zoology, Faculty of Science, Sabratha University, Libya.
*Corresponding Author: Azab Elsayed Azab, Department of Physiology, Faculty of Medicine, Sabratha University, Libya.
Citation: Fikry A. Abushofa, Azab E. Azab, H. M. A. Ghawi. (2022). Assessment of the Haematological Alterations in Cervical Cancer Patients Attending Sabratha. Clinical Oncology Research and Reports. 3(1); DOI:10.31579/2693-4787/036
Copyright: © 2022, Azab Elsayed Azab, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 01 November 2021 | Accepted: 27 December 2021 | Published: 04 January 2022
Keywords: cervix cancer; cbc; haematological parameters; sabratha national cancer institute; western Libya
Background: Cervix cancer is one of the most common cancers in women worldwide, and is the third most common malignant disease in women. It is one of the main health problems in Libyan women. Blood act as a pathological reflector of the status of exposed patient to infections and other conditions. Laboratory tests on the blood are vital tools that help detect any deviation from normal in the human body As the disease progresses, changes appear in haematological parameters which have been of relevant consideration in context of cancer patients.
Objectives: The present study aimed to evaluate the alterations in haematological parameters among cervical cancer patients in Sabratha National Cancer Institute.
Subjects and Methods: The present study was conducted on 150 cervical cancer patients, attending the National Cancer Institute of Sabratha from the 11th February, 2006 to the 3rd February, 2020. This study was approved by the Research and Ethical Committee of Sabratha University and Sabratha National Cancer Institute. Age was extracted from patient files. Also, 60 healthy individuals without any chronic disease were recruited for the control group. Blood samples were collected by vein puncture, 3 ml of venous blood withdrawn from each participant in the study by using disposable syringes under aseptic technique; they then transferred to a sterile EDTA tube, for complete blood count. The statistical significance of differences between groups was evaluated with the Mann Whitney U test.
Results: The results showed that the mean age of the cervix cancer patients was 53.37±11.6 years.RBCs count, hemoglobin concentration, Hct value, MCH, MCHC, and lymphocytes % were significantly (P<0.01) decreased compared with the healthy individuals. On the other hand, leukocytes and platelets count, mixed %, neutrophils %, PLTs/Lymph, and Neutrophils/Lymphocytes ratios were significantly increased as compared with the healthy individuals.
Conclusion: It can be concluded that a significant increase in leukocytes and platelets count, mixed %, neutrophils %, and the studied inflammation related haematological parameters and a significant decreased in lymphocytes %, RBCs count and most its indices. Further haematological studies are needed to confirm these results. Also, there is need to routinely monitor the haematological parameters and among cervical cancer patients.
CBC: complete blood count;
HPV: human papillomavirus;
IQR: interquartile range;
MCV: mean corpuscular volume;
MCH: mean corpuscular hemoglobin;
MCHC: mean corpuscular hemoglobin concentration;
NLR: neutrophil-to-lymphocyte ratio;
Neut/Lymph: Neutrophils/Lymphocytes Ratio;
PLR: platelet-to-lymphocyte ratio;
PLTs/Lymph: platelets/lymphocytes ratio;
RBCs: red blood corpuscles;
WBCs: white blood cells.
Cancer is a group of diseases that can be induced as a result of abnormal uncontrolled division of cells in the human body. Epidemiologically, cancer is the second cause related to death worldwide after heart disease (Torre et al., 2017). Among all human malignancy, cervix cancer is one of the most common cancers in women worldwide (Siegel et al.,2013), and is the third most common malignant disease in women. The incidence and mortality rate of cervical cancer are more prevalent in sub-Saharan Africa, Southeast Asia, Latin America, the Caribbean, Central and Eastern Europe, Zimbabwe, Malawi, and Uganda. Whereas, it is less prevalent in Western Asia (Torre et al., 2016). It is estimated that the highest rate of incidence of cervical cancer: in Five countries including India, China, Indonesia, Brazil, and the Russian Federation (Momenimovahed and Salehiniya, 2017). Cervical cancer is one of the main problems in Libya (El Mistiri et al., 2003). It has been found that it is the second most common tumor among females in Algeria and Morocco and the third most common tumor in Tunisia. Due to the lack of cancer screening and prevention programs in Libya, only a few cases have been reported in the eastern region of Libya. Almost 100% of all cervical cancer cases are caused by human papillomavirus which ranks as the most sexually transmitted infection worldwide (Parkin, 2006).
The Cervix is the lower part of the uterus that connects the uterus with the vagina. It is divided into two portions endocervix is covered by glandular columnar cells and ectocervix is covered by squamous cells. Almost all cases of cervical carcinoma originate in the transformation zone from the ecto- or endocervical mucosa. The transformation zone is the area of the cervix between the old and new squamocolumnar junction (Bruni et al., 2010). According to data available until 2013, the highest prevalence of human papillomavirus (HPV) (14.6%) in Tunisia for unknown reasons (Bruni et al., 2013). The prevalence of HPV in the population of western Algeria was 40% in vaginal cancers, 17% in vulvar cancers, and 33% in anal cancers (Nahet et al., 2016). The most cases of cervical cancer occur as a result of HPV- 16 and HPV- 18. High-risk types, especially HPV 16, are found to be highly prevalent in human populations (Bruni et al., 2010), whereas infection by others causes warts and benign lesions and is considered low risk (types HPV- 6 and HPV- 11) (Munoz et al., 2003).
Features of early invasive cancers of the cervix produce few symptoms in premenopausal women as vaginal bleeding after intercourse, irregular vaginal bleeding, and watery vaginal discharge, severe pelvic pain caused by tumor metastasis in bone (Peel, 1995). The incidence rate of uterine cancer increases in young adults (Bruni et al., 2010), risk factors for infection appear in women who have their first pregnancy at an early age, progesterone-based contraceptives.
Progesterone is considered to be a stimulator of HPV gene expression. Multiple sexual partners, those who have children from a young age, and sexual behavior, vitamin A, and C deficiency, and smoking are also considered as risk factors (Skegg et al., 1982) (Herrero et al., 1989).
Blood act as a pathological reflector of the status of exposed patient to infections and other conditions. Laboratory tests on the blood are vital tools that help detect any deviation from normal in the human body (Okwesili et al., 2017). As the disease progresses, changes appear in haematological parameters such as WBCs, RBCs, haemoglobin which have been of relevant consideration in context of cancer patients (Nath et al., 2014). Cervical cancer has direct impact on the haematological parameters (Nath et al., 2015). Leukocytosis has been evaluated in many studies in lung cancers and colorectal cancer (Walsh et al., 2005, Sprague et al., 2008). The association between leukocytosis and the stage of cervical cancer was demonstrated in another study (Tavares- Murat et al., 2010).
In the view of the limited availability of the extent of cervical cancer in Libya, especially in the western region, and the lack of studies published at the present time on the haematological changes in cervix cancer patients. So, the present study aims to evaluate the alterations in haematological parameters among cervical cancer patients in Sabratha National Cancer Institute.
Study design and population
The present study was conducted on 150 cervical cancer patients, attending the National Cancer Institute of Sabratha for a Pap Smear screening to detect cancerous or pre-cancerous conditions of the cervix or other medical conditions from the 11th February, 2006 to the 3rd February, 2020, were enrolled in this prospective study. This study was approved by the Research and Ethical Committee of Sabratha University and Sabratha National Cancer Institute. Age was extracted from patient files. Also, 60 healthy individuals without any chronic disease were recruited for the control group. Blood samples were collected by vein puncture, 5 ml of venous blood withdrawn from each participant in the study by using disposable syringes under aseptic technique; they then transferred to a sterile EDTA tube, for complete blood count.
Determination of Haematological Parameters
Red blood cells count, haemoglobin concentration, hematocrit value, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, white blood cells count, differential count of leucocytes, and blood platelets count were determine using an automated haematology analyzer Sysmex (KX 21) machine in Sabratha Isolation Centre laboratory.
Statistical analysis
Continuous variables were presented as medians (interquartile range [IQR]) The data were analyzed using Graph Pad Prism software version 7. The Kolmogorov-Smirnov test was used to assess the normality of distribution of continuous variables. The statistical significance of differences between groups was evaluated with the Mann Whitney U test. P-value of <0>was used to establish statistical significance.
The mean age of the cervix cancer patients included in the current study was 53.37±11.6 years (26–88 years). The results in table.1 and figures (1-3, 5,6) show that patients with cervix cancer had a significant (P< 0>) decrease in the median (IQR) of RBCs count [(x 106/μL), 3.74 (3.33-4.17)], hemoglobin concentration [(10.05 (9.225-11.18) g/dl], Hct value [30.80(26.83-33.40)], MCH [27.90(25.83-29.40) Pg], and MCHC [33.00(31.50-34.33) g/dl] compared with the healthy individuals (median (IQR) 4.11 (3.90-4.29), 12.90(12.50-13.60), 36.30(35.25 -37.88), 29.00(28.05-30.00), 34.70(34.00-35.43), respectively. Data in table.1 and figure. 4 show a none significant (P>0.05) change in median (IQR) of mean corpuscular volume (MCV) in cervix cancer patients [83.65(77.70-87.30) μ3] compared with the healthy individuals [83.00(81.00-84.15) μ3].
The results in table.2 and figures (10,12-16) show that patients with cervical cancer had a significant (P<0>3/μL) [9.07(7.08-13.30)], Mixed [,7.40(5-10)], neutrophils % [78.80(64.83-84.40)], Platelets Count (x103/μL) [268.0(200-368)], PLTs/Lymph ratio [202.3(140-346.2)], and Neutrophils/Lymphocytes ratio [5.510(2.43-10.10)], respectively compared with the healthy individuals median (IQR), 7.1 (6.6-7.475), 6 (5-7), 63 (62-66.75), 214 (201-291.8), 108 (97.10-140.7) and 2.1(1.9-2.475), respectively. Conversely, the median (IQR) of lymphocytes % in cervix cancer patients was significantly (P< 0>
The results of the current study showed that the mean age of the cervix cancer patients was 53.37±11.6 years. Similar results were recorded by El Mistiriet al., 2010 who reported that the median age of incidence of cervix cancer in eastern Libya was 50 years. Wang et al., 2017 reported that the median age of the cervix cancer patients was 51 years (range, 25- 79 years). Also, Okwesili et al., 2017 mention that the majority of the cervical cancer subjects were in the 51-60 years of age group. In addition, Gascon and Barret-Lee, 2006 reported that 70% of cervical cancer in Nigeria was seen between 26-50 years with peak age range of 34-45 years.
Anemia, leukocytosis, and markers of inflammation such as neutrophilia (Escande et al.,2016, Koulis et al., 2017) and elevated neutrophil-to-lymphocyte ratio (NLR) (Garcia-Arias et al.,2007, Tavares-Murta et al., 2010, Cho et al., 2016, Koulis et al., 2017) are most notably is tumour related as a poor prognostic marker in cervical cancer (Garcia-Arias et al.,2007, Tavares-Murta et al., 2010, Qiu et al., 2010, Mabuchi et al., 2011, Doll et al., 2013, Cho et al., 2016, Escande et al.,2016, Koulis et al., 2017).
The present study showed that RBCs count, hemoglobin concentration, Hct value, MCH, MCHC, and lymphocytes % were significantly (P<0>) decreased compared with the healthy individuals. Finding from the present study is run parallel to a previous study which indicated that a significant decrease in the RBCs count, and hemoglobin content compared with the healthy volunteers (Nath et al., 2015). Wang et al., 2017 reported that hemoglobin concentration was significantly decreased compared with the controls. Okwesili et al., 2017 found that the mean Hct value was significantly (P<0>) lower among cervical cancer patients compared to the healthy subjects. Also, the study of Gascon and Barret-Lee, 2006 showed that red cell indices, MCH, and MCV were lower among cervical cancer patients compared to controls. Al-Araji, and Hamad, 2005 reported that the hemoglobin concentration and hematocrit value were decreased in the patients with carcinoma of the uterine cervix compared with normal ranges. indicating that the patients have sever degree of anemia, that may be due to progressive bleeding as intermenstrual bleeding after intercourse as spontaneous. Decreased Hb level was reported in cervix cancer patients (Grogan et al., 1999, Fyles et al., 2000, Serkies et al., 2006).
Iron deficiency and tumor bleeding are common causes of anemia in cervical cancer (Candelaria et al., 2005). Anaemia seen in cervical cancer has the characteristics of anaemia of chronic disorder associated with low PCV. Several factors may be responsible for the high prevalence of anaemia seen among cervical cancer patients, may be due to lower socioeconomic status and poor nutrition of the former, haemorrhage associate with iron deficiency, anorexia associated with cancers generally can also be associated with nutritional anaemia seen in these cases, metastasis to the bone marrow from cervical cancer can be associated with suppression of erythropoiesis and infection in fungating malignancies may be associated with red blood cell haemolysis and leucocytosis (Okwesili et al., 2017). Also, the Nath et al., 2015 study revealed that most of the cervical cancer patients has decreased level of haemoglobin. Most of the patients having cervical cancer comes from low socioeconomic status and poor hygiene. This may be correlated because majority of patients of carcinoma of cervix comes from low socioeconomic background are malnourished with poor hygiene level. It has been reported that malnutrition and folate deficiency lead to suppression of immunity (Dunst et al., 2003, Nath et al., 2015). Folate deficiency is responsible for decreasing immunity which might have given opportunity to HPV infection which is considered to be most important factor for causation of carcinoma of cervix. Infection will lead to increase in strengthening the defense mechanism which results in increased WBC (Demirci et al., 2011, Nath et al., 2015).
In the present study, leukocytes count, mixed%, and neutrophils % were significantly increased and lymphocytes % was significantly decreased compared with the healthy individuals. These results are in coincides with the study of Al-Araji, and Hamad, 2005 who recorded that an increase in total leukocytic count in the patients with carcinoma of the uterine cervix compared with normal ranges, indicate that there are sever inflammatory reactions in the patients with uterine cervix carcinoma. The results of the study of Nath et al., 2015 who reported that there is a significant increase in WBCs count compared with the healthy volunteers. Wang et al., 2017 recorded that leukocytes count, neutrophils % were significantly increased and lymphocytes % was significantly decreased compared with the controls. Tumour cells secrete some chemokines, such as granulocyte-colony stimulating factor or angiotensin II, that cause an increase in neutrophil production from the bone marrow (McAllister and Weinberg 2014, Berna et al., 2019). Neoplasm of all types is associated with increase in neutrophils count. The natural killer cells are lymphocyte that are capable of destroying tumour cells without prior sensitization. However, many tumours down-regulate expression of class 1. Major histo-compatibility complex molecules as a way of evading immunity. Lymphocyte count may therefore decline (Okwesili et al., 2017). Also, Okwesili et al., 2017 recorded that the mean lymphocyte count was significantly (P<0>) lower among cervical cancer patients compared to the healthy subjects. Some immunosuppressive factors, such as tumour growth factor b, interleukin-10 or reactive oxygen species, derived from the tumour or tumour microenvironment decreased lymphocyte production (Whiteside 2006, Berna et al., 2019).
Determination of platelet count plays a significant role in cancer management. The prognostic significance of the platelet count has been studied in several malignancies, yielding important information about clinical outcomes (Okwesili et al., 2017). Thrombocytosis has been associated with unfavourable prognosis or advanced disease in gynaecological and other types of cancers (Gerestein et al., 2009; Gungor et al., 2009, Crasta et al., 2010, Gonzale et al., 2010).
The current study showed that a significant increased in the median of platelets count in cervix cancer patient as compared with the controls. This result is similar to the result of Okwesili et al., 2017 who observed that the mean platelet count in the cervical cancer patients was increased compared to normal controls. Also, Wang et al., 2017 recorded that platelets count was significantly increased in cervical cancer patients compared with the controls. The platelet count is an additional marker of systemic inflammation which is precipitated by the tumor formation. Proinflammatory cytokines such as IL-1 and IL-6 leads to megakaryocyte proliferation and thrombocytosis (Klinger and Jelkmann, 2002; Alexandrakis et al., 2003). Thrombocytosis may be seen in cancer patients as a result of cancer induced anaemia. A negative feedback effect on erythropoietic production in cases as a result of the anaemia could be for responsible for the thrombocytosis. Erythropoietin has a structural homology with thrombopoietin, although the latter is considerably larger than the former but roughly half of thrombopoietin at the N- terminal region (Hoffbrand and Lewis, 2001, Okwesili et al., 2017).
On the other hand, there was no statistically significant difference between the mean WBCs, and Platelets count, MCV, MCH, and MCHC of cervical cancer patients and the healthy subjects (Okwesili et al., 2017).
One of the important systemic alterations is inflammation. Inflammation is a nonspecific feature of cancer and plays an important role in various aspects of cancer involving cancer initiation, promotion, progression, metastasis and clinical features (Babu et al., 2012, Kose et al., 2015). Therefore, inflammatory markers were studied in various cancer types as indicators of invasion (Acmaz et al., 2014, Chose et al., 2015). Inflammation plays a key role in tumorigenesis and in the progression of cervical cancer (Parida S, and Mandal, 2014, Wang et al., 2017). Thrombocytosis and lymphocytopenia have been reported as a marker in host systemic inflammation (Smith et al., 2008). Kose et al., 2015 concluded that patients with uterine cervical cancer may present with leukocytosis, increased neutrophil to lymphocyte ratio and platelet to lymphocyte ratio. These cheap and easily available parameters, especially PLR, may provide useful information about the invasiveness of the cervical pathologies. The NLR, and PLR are markers of systemic inflammation with prognostic significance for cancers (Wang et al., 2017). The previous studies showed that a strong correlation between NLR and inflammation. Increased neutrophil% is accepted to endorse neoplastic progression, and it can repress antineoplastic properties of lymphocytes. Accordingly, NLR may be recognized as the marker of the balance between precancerous inflammatory state and cancerous immune state, and higher NLR might be indicative for tumor development (Proctor et al.,2012, Tas et al., 2019).Neutrophil-to lymphocyte ratio, and platelet-to-lymphocyte ratio have been found to be associated with various kinds of cancers including non-small-cell lung cancer, pancreatic adenocarcinoma, gastric cancer, over carcinoma, renal cell carcinoma, colorectal cancers, and endometrial cancers (Toriola et al., 2011, Lee et al., 2013, Pichler et al., 2013, Yildirim et al., 2013, Acmaz et al., 2014). A growing body of evidence highlights the associations between the NLR or PLR and tumor characteristics in patients with cervix cancer. Increased NLR and PLR have been shown to be associated with stage, invasiveness, prognosis, and unfavorable histopathological characteristics of cervix cancer (Kose et al., 2015, Zhu et al., 2018, Taset al., 2019). Also, Wang et al., 2017 reported that median values of NLR and PLR were higher in cervical cancer patients compared with controls and were consistently elevated during tumor progression. Increased NLR was associated with lymph node metastasis and depth of stromal infiltration, and increased PLR correlated only with LN metastasis. The pretreatment NLR or PLR value was a significant predictor of LN metastasis, which enhanced when NLR and PLR values were combined. Further, NLR and PLR were as effective for predicting distant tumor metastasis. Authors suggested that pretreatment values of NLR and PLR might be helpful to predict the presence of distant and LN metastasis in patients with cervical carcinoma, but not adequate prognostic factors for early-stage patients.
The current study showed that the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were significantly higher in cervical cancer patients compared with the healthy individuals. These results are run parallel with the result of Taset al., 2019 who found that the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were significantly higher in patients with cervix cancer than in controls. Authors concluded that, in addition to age of patients, and determination of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, that are simple, low-cost, and readily available markers of systemic inflammation, may help in decision making precancerous pathologies of the cervix.
NLR was defined as a potential marker to determine inflammation in systemic disease (Walsh et al., 2005;
Rudiger et al., 2006; Bucak et al., 2013; Ulu et al., 2013; Acmaz et al., 2014, Kose et al., 2015). However, it is well known that inflammation plays an important role in various aspects of cancer. A correlation between the increase of NLR and endometrial cancer invasiveness has been demonstrated (Acmaz et al., 2014, Kose et al., 2015).
In the current study, NLR was higher in the cervical cancer group compared to the controls. Similarly, there was an association between NLR and cervical cancer invasiveness (Tavares-Murta et al., 2010, Kose et al., 2015). It was emphasized that PLR is a novel marker for inflammation, which incorporates both hematological factors (Smith et al., 2008). The platelet-lymphocyte ratio is an inflammatory marker and has been studied in uterine cancer and uterine cancer precursor lesions (Acmaz et al., 2014, Kose et al., 2015). Furthermore, there was an association and correlation between cervical malignant lesions and PLR in the present study. Because of this, the researchers believe that PLR may be a suitable marker like NLR. The main drawback to the current study was its retrospective nature and small sample size (Kose et al., 2015). Increased NLR and PLR as a result of increased neutrophil and platelet counts may contribute to the stimulation of cancer development in patients with precancerous cervical pathologies (Tas et al., 2019).
It can be concluded that a significant increase in leukocytes and platelets count, mixed %, neutrophils %, and the studied inflammation related haematological parameters and a significant decreased in lymphocytes %, RBCs count and most its indices. Further haematological studies are needed to confirm these results. Also, there is need to routinely monitor the haematological parameters and among cervical cancer patients.
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Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
