RELATIONSHIP BETWEEN MULTIPARITY AND THE TYPES OF

HISTOPATOLOGY OF CERVICAL CANCER

Ratih Nawang Wulan1, Zaenal Abidin2, Esa Rosyida U2, Elmi Aris R2, Jajuk
Retnowari2, Eko Sih P2, Dewi Arini H2
1
Faculty Of Medicine, Universitas Airlangga, Surabaya, Indonesia
2
Faculty Of Nursing, Universitas Airlangga, Surabaya, Indonesia

Abstract: Cervical cancer is one of the most common neoplastic diseases in women in
the world. Most of the occurrences of cervical cancer occur in developing countries, so
cervical cancer becomes the main cancer for women in developing countries. The
presence of cervical cancer results in a decrease in the quality of life in women as
sufferers. The research method was case control by looking at the data from the
respondent's medical records and analyzed using chi square and logistic reggresion. The
purpose of this study was to identify the relationship between parity and the type of
cervical cancer histopathology. Most respondents were aged 36-50 years and the
incidence of SCC and adenocarcinoma with parity. Based on the results of univariate
analysis between variables obtained p = 0.036, it can be said that parity with
histopathology type is related to the strength of 0.118 and multivariate test found that 2-4
parity is more at risk of cervical cancer with histopa SCC with OR 0.037. Parity with 2-4
is the highest number in this study which suffered from squamous cell carcinoma.
Educational efforts related to the program to limit the number of births.

Keywords: Multiparity, histopathology, cervical cancer, adenocarcinoma, squamous cell

carcinoma

Introduction

Cervical cancer is one of the most common neoplastic diseases in women in the world.
The number of cervical cancer sufferers is almost 500,000 new cases every year and kills
270,000 women every year. About 85% of cervical cancers occur in developing countries, so
cervical cancer is the main cancer for women in developing countries. The presence of cervical
cancer results in a decrease in the quality of life in women as sufferers. In Indonesia, cervical
cancer is also the most common cancer among other gynecologic cancers. The incidence of
cervical cancer around 7.9% in the world ranks second in all cancers in women with a 9.3%
death incidence rate of all cancers in women in the world 1.
According to the World health organization, it is estimated that in 2020 there will be
an increase in the number of patients reaching 20 million per year. 2014 Hospital Information
System data, there were 5,349 cases of cervical cancer in women or 12.8% of total client visits.
Meanwhile, in East Java, the number of cervical cancer patients in 2015 was 4,304 and in 2016
there was an increase to 4,796 cases. The city of Surabaya is one of the biggest contributors to
cervical cancer which was reported as many as 877 cases in 2016 2.
Histopathological type of adenocarcinoma cervical cancer and squamous cell carcinoma
is influenced by several factors that are at risk for the occurrence of one of these types of cervical
cancer. The risk factors are the number of sexual partners, parity, age too early at first delivery,
duration of use of oral contraceptives and smoking, but it is still unclear which direct risk factors
can be identified for squamous cell carcinoma which is also for adenocarcinoma 3.
Adenocarcinoma of the cervical uterus has different epidemiological and biological causes than
squamous cell carcinoma. HPV infection is the main cause of both types of cervical cancer,
several studies show differences between adenocarcinoma and squamous cell carcinoma in
relation to other factors, such as smoking, and reproductive factors 4. A study conducted by
Green et al.,In the UK found risk factors for adenocarcinoma cervical cancer and squamous cell
carcinoma at the age of 20-40 years were increased parity, age at first birth, oral contraception
and duration of smoking..
The aim of this study was to find a relationship between parity and the type of cervical
cancer histopathology.

Method
This research is an analytical survey study with a case control study approach with
retrospective analysis. The case group is squamous cell carcinoma and the control group is
adenocarcinoma. The sample used in this study was 246 respondents divided into two, namely
the control group and the case. Data is obtained by collecting secondary data from medical
records. The data collection tool used is the checklist sheet. The data collected was then
tabulated and analyzed using the chi square test and logistic regression.

Result
The results of the study found variables such as age, occupation, education, parity
number and type of cervical cancer histopathology

Table 1 Distribution of respondents by age

No Age Total Percent
1 20-35 22 9.0%
2 36-50 128 52.0%
3 >50 96 39.0%
Total 246 100%
Based on the age distribution of the respondents the highest was 36-50 years with a
percentage of 52.0%.

Table 2 distribution of respondents based on education level

No Education Level Total Percent

 1 Elementary School 80 32.5%
2 Junior High School 64 26.0%
3 Senior High School 74 30.1%
4 College 28 11.4%
Total 246 100.0%
Table 2 shows the highest number of respondents based on education level are
elementary school graduates, namely 80 respondents or 32.5%.

Table 3 Distribution of respondents based on the amount of parity

No Parity Total Percent

1 0 9 3.7%
2 1 47 19.1%
3 2-4 178 72.3%
4 >5 12 4.9%
Total 246 100%
Table 3 shows the number of parity of respondents with the highest parity number,
namely 2-4 with 178 respondents or 72.3%.

Table 4 Distribution of respondents based on the type of histopathology ca cerviks

No Type Total Percent

1 Adenocarsinoma 123 50%
2 Squamous cell carcinoma 123 50%
Total 246 100%
Based on table 5 Histopathological types are divided equally because in this study using
case control.

Bivariate analysis of variable parity and type of histology Ca Cerviks

Table 5 Cross tabulation between parity and histopathology type

The Type Of Histopathology Total

No Parity Squamous cell Adenocarsinoma
carcinoma
F %
1 0 15 18 33 13
2 1 34 38 72 29
3 2-4 55 45 100 40
4 ≥5 29 12 41 18
Total 123 123 246 100
Chi Square p= 0.036
Contingency Correlation= 0.118

Based on table 5, the highest incidence of parity was found in 2-4 with the type of
histopathology of squamosa cell carcinoma as many as 55 respondents. Adenocarcinoma is
dominated by 2-4 parity with 45 respondents. Univariate analysis between variables obtained p =
0.036 which can be said that parity with histopathology type is related to the power of 0.118.

Multivariate testing of the relationship between parity and the type of histopathology of
cervical cancer using logistic regression

Table 6 results of multivariate tests on parity and histopathology relationships

Cl 95%
Parity P value OR
Upper Lower
Parity 0 0.054 1 - -
Parity 1 0.030 0.345 0.132 0.951
Parity 2-4 0.017 0.370 0.164 0.838
Parity ≥5 0.006 0.339 155 738

From the table above, it can be seen that the highest risk of cervical cancer is in parity 2-4
with a value of OR 0.370, meaning the risk of cervical cancer in parity 2-4 is 0.37 times greater
than other parities..

Discussion

1. Identification of Parity
Based on table 4 data collected by classifying parity categories with 0, 1, 2-4, and ≥5
found the highest parity is 2-4, meaning the respondents have 2-4 children (multipara). High
parity is one of the risk factors for cervical cancer. Jensen et al., stated that women who had 4 or
more times at risk of having cervical cancer were 1.9 times more than the number of women who
gave birth between less than or equal to 3 times, although this was a risk factor but this it should
be our attention to detect this group. Pregnancy and childbirth that exceeds 3 people and the
distance of pregnancy is too close will increase the incidence of cervical cancer..
The majority of respondents who have children 2-4 are aged 36-50 years. The age of
sufferers is between 30-60 years, the most between 45-50 years. This study is also in line with a
study conducted by Missaoul which shows that the average age diagnosed with cervical cancer is
at most above 40 years of age. The latent period of the prevasive phase to be invasive takes about
10 years. Only 9% of women under 35 years showed invasive cervical cancer at the time of
diagnosis, while 53% of KIS (carcinoma in-situ) was found in women over 35 years of age 7.
According to the theory, the incidence of cervical cancer increases with age and the time
it starts to become infected with HPV until it becomes invasive cancer as a multistage
carcinogenesis process that requires around 10-20 years. In addition, in old age there is also a
decrease in immunity which plays a role in destroying cancer cells, slowing growth and spread.

2. Identification of Types of Histopathology of Cervical Cancer

Based on table 6, the most histopathological type was found in squamosa cell carcinoma
with 55 respondents with 2-4 parity. The findings in this study are in line with the research of
Chen, Tong, Guo, Lau, & Zhao, who stated that histopathology terminology of cervical cancer is
divided into squamous cell carcinoma and adenocarcinoma. The most common type of cervical
cancer is found in 80% -85% of squamous cell carcinoma, with the remaining 15% -20%
followed by adenocarcinoma or adenoskuamosa carcinoma.
The incidence of squamous cell carcinoma was initially preceded by precancerous
lesions, also called cervical intraepithelial neoplasia (CIN), which is the beginning of changes to
invasive cervical carcinoma. In these precancerous lesions, cell structure changes become
abnormal. Cells change shape and size, cell nucleus enlarges, and cell cytoplasm decreases. High
cases of squamous cell carcinoma are often caused by skrinning delay so that it is known that at
the time of being squamous cell carcinoma 5.
However, this is not in accordance with Bonin, Devouassoux-shisheboran, & Gol, who
stated that in his research found the most cases of cervical cancer were adenocarcinoma.
Adenocarcinoma itself is often found at a young age that is under 35 years. In this study most of
the respondents were between 36-50 years old so that the type of adenocarcinoma is more lacey
than the type of squamous cell carcinoma

3. Relationship of Parity with Types of Histopathology of Cervical Cancer

Based on the results of the chi square test statistics the value of p = 0.036 and α = 0.05
was obtained. Parity can play a synergistic role with other factors such as HPV to increase the
risk of cervical cancer, so that parity can be a cofactor that causes cervical neoplasia. Cervical
cancer is most commonly found in women who often give birth. This is presumably due to
hormonal changes that occur during pregnancy and cervical trauma that occur during childbirth.
Trauma to the cervix and frequent treatment in the reproductive organs during childbirth can
facilitate the entry of HPV as a causative agent for cervical cancer. Changes in the composition
of the hormone progesterone and estrogen during pregnancy also cause an influence on HPV and
the development of cancer 10

In this study, women with 2-4 more parity were found as sufferers of cervical cancer.
High parity increases trauma to the birth canal. The incidence of cervical adenocarcinoma is
often associated with HPV exposure. The development of adenocarcinoma initially originates
from epithelial cells that experience genetic mutations that change their behavior 11. These
mutated cells carry out uncontrolled, immortal cell division and invade the stromal tissue below.
Circumstances that cause irreversible genetic mutations will cause this cancer to grow.
Oncoprotein from E6 will bind and make the tumor suppressor gene (p53) become inactive,
while oncoprotein E7 will bind and make the retinoblastoma (pRb) gene product become
inactive 12. This mutation of the tumor suppressor gene causes decreased proliferative and
apoptotic activity. High parity can increase the risk of cervical cancer because maintaining a
transformation zone is on the ectocervix for a long time (years) so as to facilitate direct exposure
to HPV and other cofactors 9.
 Patil, Deshmukh, Rathid, Kotgire, & Chavan found that HPV exposure is possible
because of the stimulation of the cervix in the form of trauma and inflammation during labor,
which can repeatedly cause excessive responses. Childbirth and abortion play a role in the
development of cervical cancer because of the repeated birth process or in other words having
many children, the uterine cervix will experience trauma and slow repairs, so this is the way for
precancerous conditions. This is in line with research by Zaloudek which states that
adenocarcinoma correlates with the presence of HPV invasion. As many as 76% of women with
adenocarcinoma are positively infected with HPV with repeated labor history 15.

Repeated labor takes the form of changes from the ectocervical epithelium, namely the
squamous epithelium with the endocervical epithelium, which is a ciliated layer of short cuboid /
columnar epithelium. In young SCJ women outside the external uterine os, whereas in women
over 35 years SCJ is inside the cervical canal 16. Therefore in young women, SCJ which is
outside the external uterine os is susceptible to external factors such as mutagens which will
trigger dysplasia of the SCJ. In women with high sexual activity, SCJ is located in the external os
due to trauma or muscle retraction by prostaglandins. During a woman's life physiological
changes occur in the cervical epithelium; the columnar epithelium will be replaced by a
squamous epithelium that is thought to originate from a columnar epithelial reserve. Sharma &
Pattanshetty found the process of replacing the columnar epithelium into a squamous epithelium
called the metaplasia process and occurs due to the influence of low vaginal pH after labor. High
metaplasia activity resulting in SCJ hyperactivity leads to squamous cell carcinoma.

This illustrates the increasing number of children the more at risk of developing cervical
cancer. Due to injury after childbirth and the distance of labor that is too close will cause the
virus that causes cervical cancer to enter. Cervical cancer or cervical cancer is the biggest cause
of cancer deaths for women. This cancer occurs in the cervical area, which is the part of the
uterus that connects the upper uterus to the vagina. The injury triggers HPV invasion and
facilitates abnormalities in cells around the injury. The result will be cervical cancer.

Conclusion

Based on the results of the study there is a relationship between parity and histoPA with a
value of p = 0.036 and the strength of a strong relationship with a value of 0.118. 2-4 parity is
0.370 times higher in squamous cell carcinoma. The need to improve health education programs
in the prevention of cervical cancer

Conflict Of Interest

None

Financial support and sponsorship

Author

Ethical Clearence
Ethical clearance was obtained from The Ethics Committee of the Soetomo General Hospital,
Surabaya (ethics approval number 0991/KEPK/III/2019)

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