|Year : 2015 | Volume
| Issue : 2 | Page : 104-110
Incidence and risk factors of abnormal cervical cytology in a university hospital - Saudi Arabia
Azza Ali El. Mahalli
Department of Health Information Management and Technology, College of Applied Medical Sciences in University of Dammam, Dammam, Saudi Arabia
|Date of Web Publication||16-Jun-2015|
Azza Ali El. Mahalli
College of Applied Medical Sciences, University of Dammam, P.O Box 1982, Dammam-31441
Source of Support: This project was funded by King Abdulaziz City for Science and Technology (SG-34-105), Conflict of Interest: None
Background: Cervical cancer is the sixth on the list of the most widespread cancers in Saudi Arabia. It is a preventable disease. Identifying risk factors may suggest prevention strategies. Aims: Study aimed to determine incidence of abnormal cervical cytology for the period (2004-2013) and identify its risk factors. Settings: Study was conducted in the university hospital in Khobar. Design: Study was case- control, hospital- based. Materials and Methods: Cases were Saudis with 'abnormal Pap smear' and controls were healthy Saudis. Independent variables (socio-demographic and obstetrics and gynaecology history) were collected from patients' charts and hospital database. Incidence of abnormal cervical cytology was calculated using hospital statistics. Binary logistic regression was used to model predictors of abnormal cervical cytology. Odds ratio and 95% confidence interval (CI) were calculated. Five percent (%) level of significance was used. Stepwise logistic regression was applied to identify predictors of abnormal cervical cytology. Results: Incidence of abnormal cervical cytology in Saudi Arabia was low in comparison to other countries. Findings showed that 1.8% (129 cases during the period 2004-2013) of all women screened with Pap smear had abnormal cervical cytology and 2.5% (75 cases during the period 2004-2013) of Saudi women had abnormal Pap smear results. Risk factors associated with abnormal cervical cytology were use of intrauterine device (OR 2.851, P = 0.012) and repeated pregnancies (three or more, OR 3.116, P = 0.010). However, patients of age 30 to less than 50, patients conducted Pap smear once or more, and patients with partners using condom were protective factors. Conclusions: Early Pap smear screening should be activated for prevention of cervical cancer.
Keywords: Abnormal cervical cytology, incidence, risk factors, Saudi Arabia
|How to cite this article:|
El. Mahalli AA. Incidence and risk factors of abnormal cervical cytology in a university hospital - Saudi Arabia. Saudi J Health Sci 2015;4:104-10
| Introduction|| |
Cervical cancer (CC) is the second most common cancer in women worldwide after breast cancer in both incidence and mortality. It is the sixth on the list of the most widespread cancers in Saudi Arabia (SA). Age-standardized rate for CC is 2.1 per 100,000 populations in SA.  CC is the most deadly of all the cancers in the developing countries. It is estimated that 80% of all new cases of CC will occur in those countries, resulting in approximately 250,000 deaths, and that 99% of these cases would be associated with Human Papilloma Virus (HPV). 
Etiology of CC is complex including several factors such as age; more than half of women with CC are between the ages of 30 and 55. Smoking is another considerable risk factor; it is estimated that smokers have approximately double the risk of developing CC than nonsmokers. Socio-economic status, history of abnormal Papanicolaou (Pap) smears, venereal diseases and inflammatory changes within the vagina or vulva, number of previous pregnancies,  age at first intercourse, and number of sexual partners ,, are also considered risk factors for CC.
Ever-use of barrier methods (condom and diaphragm) was reported by 6% of the cases of invasive cervical cancer.  Women diagnosed with cervical intraepithelial neoplasia grade 3 had an accelerated increased risk of acquiring invasive cancer. 
Pap smear screening test is the way of preventing CC. Early detection of cervical cell abnormalities by Pap smear has reduced the risk of CC development. This is because of timely response to abnormal changes in cervical cytology.  UK  and Western countries  showed dramatic decrease in CC incidence rates after the introduction of NHS cervical screening during late 1980s. HPV vaccination offers a promising option for lowering the disease burden in the developing world. , On the other hand, reports describing the frequency and pattern of abnormal Pap smears in developing countries using the revised Bethesda system are few.  Pattern of cervical intraepithelial lesions and carcinoma detected in Pap smears of Saudi females was studied in western  and eastern  regions of SA. However, identification of associated risk factors was not an aim in these studies. Accordingly, the study aimed to determine incidence and pattern of incidence of abnormal cervical cytology for patients screened by Pap smear in the university hospital in Khobar during the period (2004-2013). In addition, to identify risk factors of abnormal cervical cytology, identifying determinants of CC may suggest population-level prevention strategies.
| Material and methods|| |
Study was carried out in the university hospital (King Fahd Hospital of the University) in Khobar- Eastern Province, SA.
Hospital statistics for last 10 years (2004-2013) was used to calculate incidence of abnormal cervical cytology and determine its pattern. Case-control, hospital-based study was used to identify risk factors associated with abnormal cervical cytology. Cases were Saudi patients with 'abnormal cervical cytology smears'. These abnormal smears were confirmed CC, CIN, ASCUS, AGUS, Atypia and suspicious as documented in the pathology reports. However, controls were Saudi women with 'normal cervical cytology smear'. Medical records (chart review) of patients investigated with Pap smear for the last 10 years, who satisfied the inclusion criteria, were approached. In addition, patients' database (information management system of the study hospital called MYSIS) was used. Both medical records and MYSIS were used to extract socio-demographic characteristics, obstetrics, and gynaecology history. For incomplete data, telephone interview was conducted to collect the required data.
Pap smears for both cases and controls were conducted in the study hospital to ensure reliability of results. Medical records of patients who came to the hospital for screening, patients without abnormal gynaecological history, were approached. Medical records of Saudi women whose contact information was available and correct were included in the study. However, medical records with incomplete contact information and patients who refused to participate in the study via telephone interview were excluded.
Saudi patients with 'abnormal cervical cytology smear' during study period (2004-2013) were 75 in numbers. However, data were available for 63 cases. Controls counted to 375. Controls were distributed throughout study period (2004-2013) and were selected randomly via systematic random sampling technique using medical record number or pathology reports number. Case: Control ratio was planned to be 1:4 so that the study is statistically significant. However, plenty medical records of controls were available and five research assistants were responsible for data collection. Literature revealed that there is no upper limit for case: Control ratio. 
A pre-coded data collection sheet was designed based on literature review. ,,, It collected data on socio-demographic characteristics, obstetrics, and gynaecology history. (See Appendix)
Socio-demographic variables included age, marital status, education level and smoking habits. It also included the contact information needed for conducting phone interview and medical record number to access hospital database.
Obstetrics and gynaecology history included: Parity (number of deliveries), gravidity (number of pregnancies), parity after 24 years, number of Pap smears conducted, ever having a previous caesarean section (CS), history of infection with HPV, sexually transmitted diseases (STDs) and HIV/AIDS, family history of CC and use of contraceptives [oral contraceptive pills, intrauterine device (IUD) and condom for the partner].
Formal approval was taken before conducting the research. Confidentiality of the data collected was highly considered. Patients' permission was taken before telephone interview.
Pilot study was done for 30 medical records to investigate documentation of the independent variables in the medical records. Data collection sheet was revised accordingly. Some variables were cancelled as questions on income and household size were reluctant to be answered by the patients. In addition, age at first marriage, age at first birth and age of menarche (first menstruation) were removed due to problems of recall.
Data was statistically analyzed using SPSS program version 20.0. Incidence of abnormal cervical cytology was calculated for the period from 2004-2013. Frequency of abnormal cervical cytology of Saudis Vs. all patients (Saudis Vs. non- Saudis) was tabulated and displayed in bar charts. Incidence rate of abnormal cervical cytology was calculated as follows:
Number of new cases with abnormal cervical cytology divided by number of Women at risk of the disease*100
Annual incidence of abnormal cervical cytology of Saudis from 2004-2013 was tabulated and compared with that of all patients (Saudis Vs. non-Saudis). Pattern of abnormal cervical cytology over last 10 years was displayed in a line graph comparing that of all patients Vs. Saudis. Binary logistic regression analysis was used to model predictors of abnormal cervical cytology. Odds ratio (OR) and 95% CI was calculated. Five percent level of significance was used. Stepwise logistic regression model (backward deletion method) was applied. Five independent variables were statistically significant; age, number of Pap smears conducted, use of IUD and use of condom as a contraceptive method for male and number of pregnancies.
| Results|| |
Incidence increased markedly from 2010 onwards reaching its peak in 2013. Total incidence for Saudi patients was 2.5% Vs. 1.8% for all patients [Table 1] and [Figure 1].
|Figure 1: Pattern of incidence of abnormal cervical cytology in the teaching hospital in the eastern province, SA (2004-2013)|
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|Table 1: Annual incidence of abnormal cervical cytology in the teaching hospital in the eastern province, SA (2004 - 2013)|
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Results of the univariate regression analysis [Table 2] showed that mean age for cases was 45.97 ± 8.012 and for controls was 42.25 ± 10.047. Patients of age (40- < 50) represented the majority in both cases and controls (52.4% and 39.2% respectively, P < 0.05). In addition, patients who conducted one Pap smear test represented the majority in both cases and controls (33.3% and 72% respectively, P < 0.05). Patients who had conducted Pap smear tests were less likely to have abnormal cervical cytology (OR = 0.022, 0.080, 0.118 and 0.106 in chronological order, P < 0.05). Patients who used IUD were more likely to develop abnormal cervical cytology (OR = 2.788, P < 0.05). Use of condom for male was considered a protective factor (OR = 0.123, P < 0.05).
|Table 2: Univariate regression analysis of risk factors of abnormal cervical cytology of saudi patients attending the teaching hospital in the eastern province, SA (2004 - 2013)|
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The results of stepwise regression analysis [Table 3] showed that patients in age categories (30- < 40) and (40 - < 50) were less likely to develop abnormal cervical cytology (OR = 0.174 and 0.327 retrospectively, P < 0.05). Conducting Pap smear test ≥1 was considered a protective factor (OR = 0.024, 0.086, 0.135 and 0.108 respectively, P < 0.05). Patients who used IUD were more likely to have abnormal cervical cytology (OR = 2.851, P < 0.05). Use of condom for male was a protective factor (OR = 0.151, P < 0.05). Patients who had number of pregnancies ≥3 were at higher risk of developing abnormal cervical cytology (OR = 3.116, P < 0.05) [Table 4] and [Table 5].
|Table 3: Stepwise logistic regression analysis of risk factors associated with abnormal cervical cytology among saudi patients attending the teaching hospital in the eastern province - SA (2004 - 2013)|
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|Table 4: Frequency of abnormal and normal pap smear test results among all women (Saudis and Non-Saudis) in the teaching hospital in the eastern province-SA (2004 - 2013)|
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|Table 5: Frequency of abnormal and normal pap smear test results among Saudi women in the teaching hospital in the eastern province, SA (2004 - 2013)|
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| Discussion|| |
CC is one of the deadly diseases in the world. It is considered the second common cancer after the breast cancer worldwide.  The mean incidence rate of CC among 127 developing countries worldwide (19.2 cases/10 5 ) was nearly twice that of 45 developed countries (10.6/10 5 ). The International Journal of Cancer shows that the highest incidence rate of CC is in South American (34.2 cases/10 5 ), while the lowest is in Europe (16.1 cases/105), other continents like Asia and Africa takes (16.3 cases/10 5 ) and (27.9 cases/10 5 ) respectively. The variation of incidence among the different continents is probably related to the difference in religions, cultures and other factors. The Middle Eastern region had the lowest rate (5.6/10 5 ). Religion is independently associated with CC rates.  The Saudi women had lower CC incidence degree. According to the Saudi tumor registry 2007 report, CC is the thirteenth most frequent cancer in Saudi women and the sixth most frequent cancer in Saudi women between 15 and 44 years of age. The incidence rate in SA is 1.9 cases per 10 5 women. Current estimates indicate that every year 152 women are diagnosed with CC and 55 die from the disease. The total number of patients who had a Pap smear was 36.140 with an overall rate of abnormal Pap smears of 2.6%.  This is parallel to the present findings as 1.8% (129 cases during the period 2004-2013) of all women screened with Pap smear had abnormal cervical cytology results and 2.5% (75 cases during the period 2004-2013) of Saudi women had abnormal results. This low incidence rate in comparison to other countries is because SA is a Muslim country and the society and its standards make Muslim women less susceptible to HPV infection.  On the other hand, results of the present study showed that incidence of abnormal cervical cytology of all patients as well as Saudi patients has increased dramatically starting from the year 2010 onwards and the peak incidence was in year 2013 (6.1% for Saudis Vs. 4.3% for all patients). This could be referred to the fact that data of the present study was hospital- based and not community-based. The present study also showed that the incidence was higher for Saudi patients than all women for almost all years. This might refer to the fact that Saudi women had good access to conduct Pap smear tests at the teaching hospital in comparison to expatriates. Screening with Pap smear is accessible for Non-Saudis women who are working in governmental institutions or their husbands are governmental employees.
A study of CC incidence rates in UK during the period of (1975-2011) showed a remarkable decrease of rate over time, around 49% from their peak incidence rate in 1985-1987 (at 16.3 per 10 5 women) to the lowest rate in 2002-2004 (at 8.4 per 10 5 women) and it continued to decrease over the years.  While in the present study the incidence of abnormal cervical cytology was growing wobbling on the years 2004-2009 but on the last 4 years (2010-2013) the incidence was markedly growing among Saudi women. This could be attributed to the improved health awareness among Saudi females and accessibility of Pap smear in the university hospital for them. In addition, policy makers should pay their attention to the importance of implementing a national Pap smear programme as a preventive measure.
In UK, the age-specific incidence rate of CC during the period of (2007-2009) showed two peaks. The first peak was in women of age 30-34 and the second was in women of age 80-84. The earlier peak is because females of this age tend to become sexually active, hence more chance of being infected with HPV, whereas the second peak is because of the increasing cancer incidence in getting older.  In this study, stepwise logistic regression indicated that patients of age (40- < 50) were at lower risk of developing CC. The same was for patients of age (30 to less than 40). This could be attributed to the fact that women during the fertility period have more access to health care and treat health problems earlier. The study of Shield's et al., (2004) showed that patients of age (<35) were neither at higher risk nor lower risk of developing CC (OR = 1.0), while patients of age (35-44), (45-54), and (≥55) were at higher risk of developing CC (OR = 1.2, 1.7 and 1.5 respectively). 
The American Cancer Society reported 'Women who have had 3 or more full-term pregnancies have an increased risk of CC'.  This goes hand in hand with the present findings where patients who had number of pregnancies ≥ 3 were at higher risk of developing CC. Munoz et al., (2002) reported that odds ratio of developing CC in women who had seven full term pregnancies or more was (OR = 3.8). This indicated that high parity is considered a risk factor for developing CC.  In addition, the Alliance for Cervical Cancer Prevention reported in their 'Risk Factors for Cervical Cancer: Evidence to Date' that women who had (3 or 4) full-term pregnancies had 2.6 time the risk of developing CC compared to women who hadn't given birth. This was based on data from eight case-control studies on CC and two studies on carcinoma in situ from four continents.  No one really knows why this is true. There is one theory states that these women may have had more exposure to HPV infection because of having unprotected intercourse to get pregnant. Other studies have attributed this to hormonal changes during pregnancy, as it makes women more susceptible to HPV infection or cancer growth. An additional thought is that pregnant women might have weaker immune systems, allowing getting HPV infection and cancer growth.  Further studies should investigate why this risk factor increases the likelihood of developing abnormal cervical cytology.
Drain et al., (2002) found that any contraception usage was negatively associated with developing CC in developing countries.  The present study demonstrated that patients who used condom for male were less likely to develop CC (OR = 0.151, P < 0.05). This could be referred to the fact that use of condom lowers the risk of STDs. The result of the randomized clinical trial study done by Hogewoning et al., (2003) supports the present study where the use of condom resulted in a higher regression of abnormal cervical cytology (HR = 3.1) and more frequently cleared HPV infection (HR = 12.1). So, the condom was reported a statistically significant protective factor. 
The study of Castellsague et al., (2011) found that the use of IUD is a protective factor (OR = 0·55, P < 0.05). This was explained by the cellular immunity triggered by the IUD.  Researchers have theories that could explain how the IUD protects from developing CC. One theory states that the procedure of inserting the IUD may destroy HPV lesions before they become cancerous.  Other study also showed that women who had ever used IUD had a lower risk of developing CC even in women who used it for less than a year. The protective effect remained even after removing the IUD.  This contradicted the present findings where patients who has used IUD were at more risk of developing CC (OR = 2.851, P < 0.05).
The present study showed that patients who conducted Pap smear screening test once (1) or more than once (2), (3), and (4) were less likely to develop CC (OR = 0.024, 0.086, 0.135, and 0.108 respectively, P < 0.05). The study of Muñoz et al., (1993) done in Spain and Colombia showed that previous screening is considered as a protective factor (OR = 0.7, 0.5-1.0).  The findings of Chichareon et al., (1998) study supported this finding. In their study, they found that patients who had an interval for last Pap smear screening of (≥5 years) were at more risk of developing HPV which in turn may lead to developing Squamous Cell Carcinoma of Cervix (OR = 3.4, P < 0.005). In addition, they found that patients who had an interval for last Pap smear screening of (≥5 years) were at more risk of developing adenocarcinoma/adinosquamous Carcinoma of Cervix (OR = 2.4 adjusted for age) (OR = 1.8 adjusted for HPV, P < 0.05).  This is probably because Pap smear screening is used as a preventive effort to early detect and treat precancerous lesions. 
According to present findings, early screening with Pap smear should be activated for prevention of CC. Further studies should investigate why these risk factors increase the likelihood of developing abnormal cervical cytology.
| Acknowledgment|| |
Sincere appreciation is dedicated to research assistants: Munirah Alqahtani, Azza Alqurashi, Mai ALhareky, Noor ALmuhareb, and Razan ALmuhaidib. College of Applied Medical Sciences - University of Dammam, SA. They were responsible for data collection and entry. In addition, the work cannot be done without the consultation of Dr. Ahlam Al.Ghamdi, Obstetrics and Gynecology consultant at King Fahd Hospital of the University in Khobar.
| References|| |
Dowling EC, Klabunde C, Patnick J, Ballard-Barbash R, International Cancer Screening Network (ICSN). Breast and cervical cancer screening programme implementation in 16 countries. J Med Screen 2010;17:139-46.
Manji M. Cervical cancer screening program in Saudi Arabia: Action is overdue. Ann Saudi Med 2010;20:355-7.
Hall S, Reid E, Ukoumunne OC, Weinman J, Marteau TM. Brief smoking cessation advice from practice nurses during routine cervical smear tests appointments: A cluster randomised controlled trial assessing feasibility, acceptability and potential effectiveness. Br J Cancer 2007;96:1057-61.
Armstrong BK. Epidemiology of cancer of the cervix. In: Coppleson M, editor. Gynecologic Oncology. 2 nd
ed.. Edinburgh: Churchill Livingstone; 1992.
Armitage JO, Doroshow JH, Niederhuber JE. Abeloff′s clinical oncology. 5 th
ed. Elsevier Health Sciences; 2012. p. 2831.
Marcus E, Micheal H, Morken JV, Stehman F. Uterine cervix. Principals and Practice of Gynecology Oncology. 4 th
ed. Lippincott: Williams and Wilkins; 2005.
Parazzini F, Negri E, La Vecchia C, Fedele L. Barrier methods of contraception and the risk of cervical neoplasia. Contraception 1989;40:519-30.
Strander B, Hällgren J, Sparén P. Effect of ageing on cervical or vaginal cancer in Swedish women previously treated for cervical intraepithelial neoplasia grade 3: Population based cohort study of long term incidence and mortality. BMJ 2014;348:f7361.
Al-Jaroudi D, Hussain TZ. Prevalence of abnormal cervical cytology among subfertile Saudi women. Ann Saudi Med 2010;30:397-400.
World Health Organization. World Cancer Report 2008. Geneva: WHO; 2008. p. 512.
Peto J, Gilham C, Fletcher O, Matthews FE. The cervical cancer epidemic that screening has prevented in the UK. Lancet 2004;364:249-56.
Abdullah LS. Pattern of abnormal Pap smears in developing countries: A report from a large referral hospital in Saudi Arabia using the revised 2001 Bethesda System. Ann Saudi Med 2007;27:268-72.
Balaha MH, Al Moghannum MS, Al Ghowinem N, Al Omran S. Cytological pattern of cervical Papanicolaou smear in eastern region of Saudi Arabia. J Cytol 2011;28:173-7.
Hennessy S, Bilker WB, Berlin JA, Strom BL. Factors influencing the optimal control-to-case ratio in matched case-control studies. Am J Epidemiol 1999;149:195-7.
Drain PK, Holmes KK, Hughes JP, Koutsky LA. Determinants of cervical cancer rates in developing countries. Int J Cancer 2002;100:199-205.
Ofelia B, Urcia JC, Barmim A. Tumor registry annual report (2007). Oncology centre research unit. King Faisal Specialist Hospital and Research Centre, 2009.
Khalid S, James B, Nisrin A, Power P. Cervical cancer prevention in Saudi Arabia: It is time to call for action. Open Womens Health J 2002;6:1-5.
Shields TS, Brinton LA, Burk RD, Wang SS, Weinstein SJ, Ziegler RG, et al
. A case-control study of risk factors for invasive cervical cancer among U. S. women exposed to oncogenic types of human papillomavirus. Cancer Epidemiol Biomarkers Prev 2004;13:1574-82.
American Cancer Society. American Cancer Society Prevention, Early Detection, and Survivorship Guidelines. Available online from: [Last accessed on 2015 Jan 01].
Muñoz N, Franceschi S, Bosetti C, Moreno V, Herrero R, Smith JS, et al
., International Agency for Research on Cancer. Multicentric Cervical Cancer Study Group. Role of parity and human papillomavirus in cervical cancer: The IARC multicentric case-control study. Lancet 2002;359:1093-101.
Alliance for Cervical Cancer Prevention. Risk factors for cervical cancer: Evidence to date. Cervical Cancer Prevention. Available online from: [Last accessed on 2015 Jan 01].
Hogewoning CJ, Bleeker MC, van den Brule AJ, Voorhorst FJ, Snijders PJ, Berkhof J, et al
. Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: A randomized clinical trial. Int J Cancer 2003;107:811-6.
Castellsagué X, Díaz M, Vaccarella S, de Sanjosé S, Muñoz N, Herrero R, et al
. Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: A pooled analysis of 26 epidemiological studies. Lancet Oncol 2011;12:1023-31.
Muñoz N, Bosch FX, de Sanjosé S, Vergara A, del Moral A, Muñoz MT, et al
. Risk factors for cervical intraepithelial neoplasia grade III/carcinoma in situ
in Spain and Colombia. Cancer Epidemiol Biomarkers Prev 1993;2:423-31.
Chichareon S, Herrero R, Muñoz N, Bosch FX, Jacobs MV, Deacon J, et al
. Risk factors for cervical cancer in Thailand: A case-control study. J Natl Cancer Inst 1998;90:50-7.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]