2021 Volume 8 Issue 2

Effect of Hyperestrogenemia on the Development of Cervical Intraepithelial Neoplasia in the Case of Human Papillomavirus

Denisova Evgeniya Vladimirovna, Videneva Anastasia Petrovna, Sivun Inna Vyacheslavovna, Andrusenko Svetlana Fedorovna, Melchenko Evgeniy Ale-xandrovich, Kadanova Anna Anatolyevna

The article describes the study of the hormonal status of the human papillomavirus (HPV) carrying patients with the developed low-severity squamous intraepithelial lesion (LSIL). The aim of the study was to identify the relationship between elevated serum estradiol levels and the development of mild cervical intraepithelial neoplasia (CIN I). The number of analyzed samples included in the control and experimental groups was determined. Cytological preparations of cervical scraping were prepared and stained by the automated BD PrepStain system. The genotyping of HPV was carried out by sampling the material of the cervical canal. The hormonal status of patients in three age groups was analyzed. The results of the cytological examination, PCR, and hormonal analysis of the groups were compared with each other. In most patients of the experimental group, an increase in serum estradiol, prolactin, cortisol, and FSH was noted. It was also revealed that the majority of patients with elevated levels of serum estradiol had cervical intraepithelial neoplasia (CIN I). It was experimentally established that the percentage of dysplasia development with elevated estradiol levels has similar values in the case of HPV-16, HPV-18, and other genotypes.

How to cite this article
Vladimirovna D E, Petrovna V A, Vyacheslavovna S I, Fedorovna A S, Ale-xandrovich M E, Anatolyevna K A. Effect of Hyperestrogenemia on the Development of Cervical Intraepithelial Neoplasia in the Case of Human Papillomavirus. Entomol Appl Sci Lett. 2021;8(2):37-41. https://doi.org/10.51847/kAWEswTfjK
Vladimirovna, D. E., Petrovna, V. A., Vyacheslavovna, S. I., Fedorovna, A. S., Ale-xandrovich, M. E., & Anatolyevna, K. A. (2021). Effect of Hyperestrogenemia on the Development of Cervical Intraepithelial Neoplasia in the Case of Human Papillomavirus. Entomology and Applied Science Letters, 8(2),37-41. https://doi.org/10.51847/kAWEswTfjK

Assessment of the Relationship between ABO Blood Group and Susceptibility, Severity, and Mortality Rates in COVID-19

Bahar Mahmood Baig1, Abdolhakim Abarian2, Siamak Baghaei3, Sima Soroush4, Somayeh Ataee Rad5, Soodabeh Pooromidi5, Ehsan Moradi-Joo6, Bita Gorjizadeh7, Mohsen Davarpanah8*


1School of Nursing and Midwifery, Islamic Azad University, Tehran Medical Branch, Tehran, Iran.

2Department of Pediatrics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

3Department of Internal Medicine, Islamic Azad University, Ahvaz Branch, Ahvaz, Iran.

4Department of Pediatric Nursing Education, Behbahan Faculty of Medical Sciences, Behbahan, Iran.

5School of Nursing and Midwifery, Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran.

6Faculty of Management and Medical Information Sciences, Kerman University of Medical Sciences, Kerman, Iran.

7Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz Iran.

8Educational and Therapeutic Hospital of Sina Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.


A relationship has been identified between the blood group and infectious diseases. COVID-19 is an infection caused by a new coronavirus designated as SARS-CoV-2, which has rapidly spread worldwide. In this retrospective study, COVID-19 patients who were referred to Razi Hospital in Ahvaz from February 2020 to May 2020 were evaluated and analyzed using SPSS v.16.0. The relationship between the ABO blood group and COVID-19 was assessed using the Kruskal Wallis test and Spearman correlation coefficient.

The frequencies of blood types O, AB, B, and A were 40.2, 11.8, 25.5, and 22.5%, respectively, Among the 8016 COVID-19 patients, the frequencies of blood types O, AB, B, and A were 41.9, 9.3, 25.7, and 23.1%, respectively, and no significant difference was observed in terms of the distribution of blood groups between the healthy and infected people (P = 0.34, 95% CI = 0.66-1.23). In addition, patients admitted to the ICU ward had blood groups of O, AB, B, and A, with a percentage of 21.3, 31.29, 33.6, and 35.3%, respectively. Furthermore, dead patients had A, B, AB, and O blood types with a percentage of 10.0, 11.4, 11.05, and 16.3%, respectively. A significant relationship was observed between the blood group and disease severity and death in COVID-19 patients (p=0.05, 95% CI = 1.02–1.73). The study showed that people with blood types A and O are at higher and lower risk of infection, severity, and death from COVID-19, respectively.

Keywords: SARS-CoV-2 COVID-19, ABO blood group, Infection, Severity, Death.



Currently, human papillomavirus (HPV) is one of the most common infections worldwide. Persons of reproductive age, in particular, young women aged 18-35, are at higher risks [1]. The risk of infection is associated with a high risk of developing cervical cancer [2]. As a rule, in this pathology, HPV WRC is detected in 99.7 % of cases [3]. The risk of infection increases in the absence of barrier contraception, features of sexual behavior, or the presence of concomitant infections. The virus's contagiousness is quite high – 80% with a single sexual contact [4]. About 660 million people worldwide are infected with HPV. About 30 million cases of CIN I and about 10 million cases of CIN II-III are diagnosed annually [5-7]. According to Russian studies, in some regions, the HPV incidence rate is 120-150 per 100 thousand people, and the national average is 20 per 100 thousand people. According to the WHO, about 500 thousand cases of cervical cancer are reported annually in the world [8].

The human papillomavirus causes damage to the mucous membranes of the upper respiratory tract, rectum, and genitals. Morphologically, cellular proliferation, which is accompanied by the replication of the viral genome, manifests itself in the form of warts and papillomas, as well as the appearance of coilocytosis. The flat and glandular epithelium of the cervix is affected by HPV of high carcinogenic risk. The transformation zone is the most vulnerable. Viral DNA is embedded in the DNA of cells and the expression of the E6 and E7 genes increases. The products of these genes reduce the effect of the tumor suppressor protein p53 and retinoblastoma protein pRb. Normally, p53 is responsible for initiating the replication of the cell's DNA as it controls the phases of its cycle and blocks tumor processes. The expression of the E6 gene leads to the synthesis and accumulation of the E6 protein, which, in combination with the E6-AR protein, participates in the degradation of p53 and reduces its amount in the cell. In the future, this leads to cell immortalization [9]. The pRb protein blocks the replication process when DNA damage is detected. The total action determines the transition of the cell from the G1-phase to the S-phase. There is an E2F kinase that provides this transition. Normally, it is in a complex with pRb, so it is inactive. The product of the E7 gene - the p16ink4α protein- separates this complex. It is also involved in the methylation of suppressor genes, which leads to their instability. Cell proliferation increases but the cells do not reach maturity. The protein p16ink4α is an early marker of the precancerous condition of the cervix, so its detection is of great diagnostic importance [10].

The development of cervical intraepithelial neoplasia in the case of human papillomavirus is influenced by many factors. According to some authors, hormonal imbalance can provoke the phenomenon of cervical neoplasia [11]. In our work, we evaluated the effect of elevated estradiol levels on the development of CIN I. As is known, estradiol (E2) is converted to 16α-hydroxy estrone (16α-ONEE1) and 2-hydroxy estrone (2-ONEE1) as a result of metabolic reactions. The first has an increased carcinogenic effect as it binds very strongly to estrogen receptors through covalent bonds. 2-ONE1, on the contrary, normalizes cell growth. 16α-hydroxy estrone stimulates the synthesis of the oncoprotein E7, thereby accelerating the process of tumor transformation [12].


The study was conducted in the clinical and diagnostic laboratory of the Stavropol Regional Clinical Hospital in Stavropol City. We examined 28 patients with the result of cytological examination of cervical scraping "LSIL"(Figure 2) and "LSIL CIN I"(Figure 3), (according to the Bethesda classification), and 23 patients with a satisfactory result - NILM (control group), (Figure 1). In all patients, the presence of HPV was confirmed by PCR. Patients infected with HPV of several genotypes, representing different carcinogenic risks, belonged to the group of the most oncogenic type.


Figure 1. Surface cells of squamous epithelium with small nuclei and abundant cytoplasm. They are located mostly scattered. The result is NILM. 1. Cell nuclei. 2. Cytoplasm. The preparation was made by the method of liquid cytology, stained according to Papanicolaou. x400



Figure 2. The lesion of the squamous epithelium of a low grade. HPV. The result is LSIL. 1 - Koilocytes - intermediate cells of stratified squamous epithelium, hyperchromic nucleus, pronounced perinuclear clearing zone. 2 - Dyskeratocytes - cells of squamous epithelium, polygonalelongated, with hyperchromic nuclei and dense cytoplasm. 3 - Parabasal cell. The preparation was made by the method of liquid cytology, stained according to Papanicolaou. x400


Figure 3. Dysplasia of the cervical epithelium of low grade. The result is LSIL CIN I. 1 - a layer of parabasal cells. 2 - Atypical cells of irregular, elongated shape, with signs of dyskaryosis, the cytoplasm is intensely colored. The preparation was made by the method of liquid cytology, stained according to Papanicolaou. x400


Cytological preparations were made and stained by Papanicolaou using the automated BD PrepStain system. The liquid method of preparation is preferable to the traditional one since the endocervix and ectocervix cells are included into the test sample. Also, the quality of the preparation by liquid cytology method is much higher than that prepared by a laboratory assistant or a gynecologist on their own.

In order to determine the relationship between the development of mild cervical neoplasia (CIN I) and hormonal status, an immunochemical analysis of blood serum was performed in 28 patients with the result of cytological studies "LSIL" and "LSIL CIN I" and confirmed HPV. In 23 patients of the control group, the result of carrying HPV was confirmed by PCR and hormonal status studies were also conducted. In the study, all patients were divided into three age categories. In women of reproductive age, the study was conducted on days 4-7 of the menstrual cycle.

Statistical data analysis was carried out by the method of variation statistics using "Microsoft Excel 7.0".


The study of the hormonal status, according to some researchers, can determine the prognosis of the development of certain pathologies. Estrogens can influence the development of cervical neoplasia since this pathology develops in the transformation zone – the area of the junction of the multilayer flat epithelium of the vaginal part of the cervix and the glandular epithelium of the cervical canal.

When studying the hormonal status of the experimental group of patients, it was revealed that all 28 had deviations according to the results of the study. Of the 23 patients in the control group, 12 had normal serum hormone levels. When summarizing the data obtained, it was revealed that among the patients of the control group, hyperestrogenemia was observed in 21.7% of cases, in 26.1% there was an increase in other hormones, and in 52.2 % of cases, the result of the hormonal study was normal.

Among the 28 patients of the experimental group, all results of the study of hormonal status had deviations. In 79% of cases, there was a significant increase in estradiol, and in 21% of cases, there was an increase in other hormones.



Table 1. The level of estradiol in the blood serum of patients of different age categories in the control and experimental groups


Level of estradiol in the blood serum


19-25  years old

26-40 years old

41-59 years old

Control group

68.243 ± 16.628*

116.382 ± 64.165*

177.393 ± 25.856*

Experimental group

210.678 ± 23.032*

304.796 ± 121.784*

319.135 ± 101.292*

Note: * indicates the significance of the differences between the values p ≤ 0.05


Figure 4. The level of estradiol in the blood serum of patients of different age categories in the control and experimental groups

Note: * indicates the significance of the differences between the values p ≤ 0.05


In women aged 19-25, an increase in serum estradiol by 3 times was noted (p < 0.05) in comparison with the control group. In patients aged 26-40, an increase of 2.6 times (p < 0.05) was observed in the estradiol level compared with the control group. In the age group between 41 and 59, the increase in estradiol was 1.8 times (p < 0.05) in comparison with the control one (Table 1 and Figure 4). According to the cytological study, 19 patients of the experimental group with elevated estradiol levels had a mild degree of dysplasia (CIN I). As it is known, HPV-16 and HPV-18 play the greatest role in the occurrence of cervical neoplasia and breast cancer. However, according to the results of the PCR study, out of 86% of patients with hyperestrogenemia and CIN I only 41% had the most carcinogenic genotypes (Figure 5).


Figure 5. Number of cases of HPV-16, HPV-18, and other genotypes of the virus in hyperestrogenemia and the presence of CIN I



The study of the endocrine profile in women can help determine the prognosis of the course of certain pathologies. Estrogens, in particular estradiol and its metabolites, contribute to the occurrence of hyperplastic processes in the female reproductive organs. These factors can be considered from the perspective of synergy. Hyperestrogenemia is a favorable factor for the development of HPV-associated cervical intraepithelial neoplasia. In our study, 86% of patients with elevated estradiol levels in case of HPV had cervical intraepithelial neoplasia. It should be noted that out of 86% of cases of hyperestrogenemia and "LSIL CIN I", the most carcinogenic HPV genotypes – 16 and 18 – were found in 41%. It means that estrogens can influence the development of CIN in the case of the human papillomavirus.






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Entomology and Applied Science Letters is an international peer reviewed publication which publishes scientific research & review articles related to insects that contain information of interest to a wider audience, e.g. papers bearing on the theoretical, genetic, agricultural, medical and biodiversity issues. Emphasis is also placed on the selection of comprehensive, revisionary or integrated systematics studies of broader biological or zoogeographical relevance. Papers on non-insect groups are no longer accepted. In addition to full-length research articles and reviews, the journal publishes interpretive articles in a Forum section, Short Communications, and Letters to the Editor. The journal publishes reports on all phases of medical entomology and medical acarology, including the systematics and biology of insects, acarines, and other arthropods of public health and veterinary significance.
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