Characteristics of Cervical Pre-Cancerous Lesions at Sanjiwani General Hospital in January-December 2022

Pre-cancerous lesions are cell changes that start on the surface of the cervix near the squamocolumnar junction (SCJ). Cervical cancer can be prevented through early identification and treatment. These pre-cancerous lesions can be identified through methods such as pap smears, visual inspection with acetic acid (VIA), and human papillomavirus (HPV) DNA tests. This study aims to determine the characteristics of cervical pre-cancerous lesions at Sanjiwani General Hospital. This is a descriptive observational study design with a cross-sectional approach at Sanjiwani General Hospital from January to December 2022. The inclusion criteria were patients who had pap smear screening and were recorded entirely in the examination data archive at the Anatomical Pathology Laboratory of Sanjiwani General Hospital in 2022. The exclusion criteria were Pap smear results with inadequate pap smears to be evaluated. The result was obtained from secondary data from patient medical records, determined by the total sampling technique, and will be processed using the IBM SPSS Statistics Version 26 application. In total, 35 samples met the research criteria. All samples (100%) showed positive findings on the VIA test. The most found on the pap smear screening was 15 samples (42.9%) with NILM and followed in succession by eight samples (22.9%) with ASC-US, seven samples (20%) with ASC-H, three samples (8.5%) LSIL, and two samples (5.7%) with findings of HSIL. Most patients with Pap smears at Sanjiwani General Hospital in 2022 will be in the age group of 41-50. Based on obstetric and gynecological history, most respondents had parity ≥ 3, age at sexual intercourse ≥20 years, number of sexual partners was only one, and had not experienced menopause. Most patients use hormonal contraception, have no family history of cervical cancer, and have never been vaccinated or screened for HPV. Most of the pap smear findings were NILM, with the most abnormalities found being ASCUS.


I. INTRODUCTION
Cancer is one of the world's most common causes of death, with around 8.2 million deaths in 2012 based on World Health Organization (WHO) statistics, and it shows a similar trend in recent years [1].Cancer is an abnormal cell growth and division that is malignant, autonomous, grows fast, and uncontrollable [2].Cervical cancer is the fourth most common cancer in women [3].
Cervical cancer is cancer whose growth starts from the cervical cells of the uterus.One of the most common causes is the Human Papillomavirus (HPV), with more than 75% of cases caused by high-risk HPV 16 and 18 [4].It is estimated that there will be 604,000 new cases in 2020 with 342,000 deaths [3].Cervical cancer is the second leading cause of death after breast cancer in lower Human Development Index (HDI) settings.As many as 85% of deaths from cervical cancer occur in underdeveloped or developing countries.It is estimated that the death rate in these countries is 18 times more than in wealthier countries [5].According to 2020 Global Cancer Observatory (GLOBOCAN) data, there were 36,633 (17.2%) new cases of cervical cancer diagnosed in Indonesia which is in second place after breast cancer [6].Cervical cancer begins with abnormal cell changes characterized by dysplastic changes in the cervical epithelium.Pre-cancerous lesions are cell changes that start on the surface of the cervix near the squamocolumnar junction (SCJ).The lesions will develop into cancer unless detected and treated early [2], [7].Cervical cancer can be prevented through early identification and treatment.One way is through screening for pre-cancerous lesions.These pre-cancerous lesions can be identified through methods such as pap smears, visual inspection with acetic acid (VIA), and human papillomavirus (HPV) DNA tests.Currently, pap smear and VIA are the most widely applied examinations [2].
A pap smear is a cervical cancer screening method by taking a cytological sample from the cervix.The American College of Obstetricians and Gynecologists (ACOG) recommends that women ages 21-29 have a pap smear every three years.Screening is carried out every five years for women aged 30-65.Screening may need to be done more frequently in special populations such as women infected with HIV, immunocompromised, women exposed to diethylstilbestrol while in utero, and women previously treated for CIN 2, CIN 3, or cervical cancer.However, screening is not recommended for patients under 21 years of age, and screening should be discontinued after 65 years of age [8].The formation of acetowhite indicated a positive VIA test after 1 minute of giving acetic acid to the cervix [2].
Cervical cancer screening is essential in determining the prognosis of the disease.Early disease detection is expected to reduce mortality by providing appropriate early action.However, few studies are still on the characteristics of cervical pre-cancerous lesions reported in Indonesia, especially in Bali.This study aims to determine the characteristics of cervical pre-cancerous lesions at the Sanjiwani General Hospital.

II. METHODS
This research was conducted using a descriptive observational study design with a cross-sectional approach to determine the characteristics of pre-cancerous lesions.The study was conducted at Sanjiwani General Hospital from January to December 2022.The research subjects were selected from a population that met the inclusion criteria and did not meet the exclusion criteria.The inclusion criteria for this study were patients who had pap smear screening with positive VIA examination and were recorded entirely in the examination data archive at the Anatomical Pathology Laboratory of Sanjiwani General Hospital in 2022.The exclusion criteria in this study were pap smear results with inadequate pap smears to be evaluated.The result was obtained from secondary data from patient medical records.The number of samples is determined by the total sampling technique, the method of deciding research samples by taking all population members as samples or respondents.In this case, all subjects who met the inclusion criteria during the study period were sampled.The characteristic criteria examined in this study were age, education level, employment status, smoking status, parity, age at first sexual intercourse, number of sexual partners, menopausal status, history of contraception, family history of cervical cancer, history of HPV vaccination, and screening history, and VIA and pap smear examination findings.The data obtained will be processed using the IBM SPSS Statistics Version 25.The analysis will be carried out descriptively and will be presented in the form of tables and narratives.

A. Sociodemographic Characteristics
In total, 35 samples met the research criteria.The results showed that patients with pre-cancerous lesions were most commonly found at 41-50, as many as 15 people (43%).Patients in the 21-30 year range were four people (11.4%), 31-40 year age range were 13 people (37.1%), and the lowest number was at the age of 51-60 years (8.5%).Based on their level of education, six people (17.1%) had no education or only had primary education, 20 people (57.1%) had secondary education, and nine people (25.8%) had tertiary education.Based on their job status, the characteristics of the sample in this study were as many as 16 people (45.7%) did not work, and 19 19 people had jobs.Most of the study sample were non-smokers, namely as many as 30 people (85.7%).
The distribution of sociodemographic characteristics of pre-cancerous lesions at Sanjiwani General Hospital in this study can be seen in Table I.

B. Obstetric and Gynecological Characteristics
The results showed that most samples had parity greater than or equal to three (62.9%).For a history of first sexual intercourse, 14 people (40%) had sexual intercourse for the first time before they were 20 years old, and 21 people (60%) had a history of first sexual intercourse when they were ≥20 years old.Most patients with pre-cancerous lesions have not experienced menopause (65.7%).Most of the respondents used hormonal contraception (68.6%); namely, six people (25%) used hormonal pills, eight people (33.3%) took hormonal injections, and ten people (41.7%) used implants.Only eight people (22.8%) had a family history of cervical cancer, and the rest (77.1%) did not find any history in the respondent's family.Only six people (17.1%) had ever had an HPV vaccination, and 29 people (82.9%) had never been vaccinated against HPV.The distribution of obstetric and gynecological characteristics of pre-cancerous lesions in this study can be seen in Table II.Based on screening history, 25 people (71.4%) had never screened for cervical cancer; ten people had been screened, which is eight people once, and two people screened more than once, with history of 6 participants (60%) was screened using the IVA method, and 4 participants (40%) were screened using the pap smear method.The distribution characteristics of the respondent's screening history in this study can be seen in Table III.

C. Cervical Pre-cancerous Lesions
All samples (100%) showed positive findings on the VIA test.Then the description of pre-cancerous lesions, the most found on the pap smear screening was 15 samples (42.9%) with negative findings for intraepithelial lesion or malignant (NILM) and followed in succession by eight samples (22.9%) with atypical squamous cells of undetermined significance (ASC-US), seven samples (20%) with ASC-cannot exclude HSIL (ASC-H), three samples (8.5%) low grade squamous intraepithelial lesion (LSIL) ), and two samples ( findings of high grade squamous intraepithelial lesion (HSIL).The distribution of cervical pre-cancerous lesions at Sanjiwani General Hospital in this study can be seen in Table IV.

IV. DISCUSSION
This study showed that the age group that screened the most was 41-50 (43%), and the lowest was 51-60 (8.5%).This finding shows that there is an agreement with several previous studies.One study in Addida Ababa, Ethiopia, showed that subjects aged 40-49 years were more likely to have cervical pre-cancerous lesions than subjects aged 30-39 [9].Similar results were also shown in another study in Jimma, Ethiopia which found that the older the age, the greater the risk of experiencing invasive cervical cancer [10].Similar characteristics were also found in a study at Sanglah Hospital, Denpasar, Bali by [7], the study in Uganda by [11] and the Rwandan study by [12] which show the majority of cervical pre-cancerous lesions were diagnosed in the third and fourth decades of life.The potential for exposure to the HPV virus to cause symptoms to develop into invasive cancer is a multistage process of carcinogenesis that requires quite a long time.In old age, immunity will also decrease, which plays a role in the development of cancer cells.This could be why the number of cervical cancer screenings is mostly done at age 41-50 [13].
Based on the level of education, most of the sample had secondary education (57.1%).One factor that influences the level of cervical cancer screening participation is the level of education.Research by [14] suggests that lower education levels are more reluctant to carry out screening.The same result was also shown in a study by [15].However, different results were obtained in a study by [16] and [17].In that study, it was found that there was no relationship between education level and participation in cervical cancer screening.This difference in results may be due to the small number of samples, differences in sociodemographic conditions, and cultural characteristics [18].
In this study, 62.9% of participants had parity ≥ 3 times.A study by [7] found that pre-cancerous lesions were more common in the multiparous group (73.9%).Reference [19] found that patients with a parity of less than two have 2.12 times the possibility of developing pre-cancerous lesions compared to someone with more parity.This relates to the possibility that high parity increases the risk of cervical squamous cell carcinoma among HPV-positive women, which may be due to cervical trauma during labor, abortion, or hormonal status during pregnancy which may facilitate the acquisition or persistence of HPV [19], [20].
Regarding sexual behavior, in this study, 60% of studies had their first sexual intercourse at more than 20 years old.A systematic review and meta-analysis of cervical precancerous lesions in women in Ethiopia during 2010-2019 showed that there was no association between age at first sexual intercourse and the incidence of pre-cancerous lesions [21].While another study by [7], [11], [22] and [23] reported that pre-cancerous lesions were higher in the group having first sexual intercourse at the age of under 20 years.Younger age at first sexual intercourse is associated with an increased risk of HPV infection.Young age is a vulnerable period of the process of metaplasia at puberty.In young women, the SCJ is located outside the external uterine ostium, making it more susceptible to external factors such as mutagens that trigger dysplastic epithelial changes [7].
In this study, 28.6% of participants had more than one sexual partner.Based on the Systematic Review and Meta-Analysis in Ethiopia found that women with more than one sexual partner develop more pre-cancerous lesions [21].Women with multiple sexual partners were identified as a significant factor associated with increased pre-cancerous lesions [19].In this study, 34.3% of the screened patients were menopausal, and 65.7% were not yet menopausal.A study by [24] and [25] revealed no relationship between menopausal status and the incidence of cervical cancer.
We obtained a history of contraceptive characteristics.It shows that most participants use hormonal contraceptives (68.6%).Reference [26] reported that the risk of precancerous lesions was increased in women using oral contraceptives.The oral contraceptive pill causes a folate deficiency, reducing the mutagen's metabolism, and at the same time, estrogen is likely to be one of the co-factors that can make HPV DNA replication.In IUD users, long-term immune response induces small local foci in the endocervix and cervix, triggering local mucosal changes toward cervical pre-cancerous lesions.Use of IUD contraception increases the risk of cervical cancer by up to 30% [27].
In this study, it was reported that only 17.1% had carried out the HPV vaccination.A study that included 26 trials with a total of 73,428 samples revealed convincing evidence that the HPV vaccine can prevent cervical pre-cancerous lesions in adolescents and young women aged 16-26.Mainly for HPV16/18 related lesions.There was no increased risk of severe side effects after HPV vaccination [28].A decrease in the incidence of CIN2+ was found when the HPV vaccine was introduced at TennCare, especially in the 18-20 year age group [29].
The results of this study showed that only 28.6% of study participants had ever been screened.Cervical cancer screening is an approach to preventing cervical cancer.A systematic review of population studies in China found a strong association between delays in pap smear screening and the risk of cervical carcinoma due to HPV infection [30].Cytological screening has led to a significant reduction in the incidence and mortality due to cervical cancer.Most countries have also implemented it to ensure continuous quality improvement [31].
The most pap smear cytology finding in this study was NILM.The study found that pre-cancerous lesions were 57.1%, with the most common pre-cancerous lesion being ASCUS (22.9%).These results were found following other studies in which standard features were commonly found on Pap smear screening.The study by [32] reported that 728 women (40.6%) gave a regular pap smear appearance.The most common abnormality found was inflammation (29.9%).Other abnormal findings were ASCUS (6.5%), LSIL (11.7%),HSIL (6.2%), atypical glandular cell (AGC) (0.7%), and suspicion for malignancy (0.2%).A two-city study in Cameroon reported that an overall prevalence of precancerous cervical lesions was 12.2%.The abnormalities found in this study were ASCUS (7.9%), LSIL (66.4%), and HSIL (25.7%) [19].In another study in Ghana [33], the prevalence of pre-cancerous lesions was 6.2%.In Rwanda, it was 20% [34] and in Nigeria, 22.6% [35].Similar results were found in the study by [7] in a tertiary hospital setting in Bali, where the most common cytological findings were ASCUS (43.2%), followed by LSIL (20.2%),ASC-H (19.2%), and lowest HSIL (17.4%).Differences in the prevalence of cervical pre-cancerous lesions may be due to sociodemographic characteristics, research methodologies, population culture and attitudes, availability of screening centers, and accuracy of screening test kits.One of them is the level of participation and awareness of screening which is still low in the community [19].Patients with low-grade lesions usually improve to ASCUS and return to normal without treatment.Usually, this process takes around 7.8 months for low-risk-type HPV and 13.8 months for high-risktype HPV.High-grade lesions will develop into cervical cancer within 10-20 years [7].

V. CONCLUSION
Most patients with Pap smears at Sanjiwani General Hospital in 2022 will be in the age group of 41-50.The majority of respondents have secondary education, has a job, and is a non-smoker.Based on obstetric and gynecological history, most respondents had parity ≥ 3, age at sexual intercourse ≥20 years, number of sexual partners was only one, and had not experienced menopause.Most patients use hormonal contraception, have no family history of cervical cancer, and have never been vaccinated or screened for HPV.Most of the pap smear findings were NILM, with the most abnormalities being ASCUS.

CONFLICT OF INTEREST
Authors declare that they do not have any conflict of interest.

TABLE II :
CHARACTERISTICS OF THE RESPONDENT'S OBSTETRICS AND GYNECOLOGY HISTORY