Cervical Cytological Findings among Women Attending a Tertiary Care Hospital in Sana’a, Yemen

Objective: To determine the frequency and pattern of abnormal cervical smear findings among women attending the University of Science and Technology Hospital (USTH) in Sana'a city. Methods: This study is a retrospective, cross-sectional study. Records of women examined by conventional Pap smears in the Histopathology Laboratory of USTH over a 4-year period (from January 2013 to December 2016) were retrieved and analyzed for abnormalities according to the Bethesda system. Results: Of 688 cases, 599 with satisfactory records were analyzed. The mean age of the cases was 39.18±10.23 years (range: 19–75). Epithelial cell abnormalities (ECAs) were found in 47 cases (7.8%), and these were categorized as follows: ASCUS in 4.5% (27/599) of cases followed by atypical glandular cells (AGC) (2.2%; 13/599) and LSIL (0.5%; 3/599), while ASCH and HSIL abnormalities were equally observed among 0.3% (2/599 each) of cases. Of patients positive Pap smear findings, ASCUS was the most frequent type of ECA (57.4%; 27/47) followed by AGC (27.7%; 13/47) and LSIL (6.4%; 3/47), while ASCH and HSIL were the least frequent ECAs among Yemeni patients. ECAs were significantly more prevalent among women aged >40 years (10.8%) compared with those aged <40 years (5.5%). Conclusions: Cervical cytological abnormalities are not uncommon among women in Yemen, where the AGC is frequent among about a third of women with abnormal Pap smear findings and affects women of different ages. This requires more attention and training of doctors to master good sample taking, preparation and diagnosis with a focus on glandular changes.


Introduction
Cervical cancer is considered as the fourth leading cause of female cancers worldwide. More than 528,000 new cases were estimated in 2012, of which about 86% occurred in the least developed countries. Moreover, approximately 266,000 females died of cervical cancer, representing 7.5% of all female cancer deaths (1). In developing countries, cervical cancer is the second most frequently diagnosed cancer after breast cancer and the third leading cause of cancer death after breast and lung cancers (1). Its highest incidence rates are in Eastern Africa, while its lowest rates are in Western Asia (1). Such a variation may reflect differences in predisposing risk factors, prevalence of human papillomavirus (HPV) infection as well as the use of screening and diagnostic methods (1-3).
Infection with HPV is the main risk factor for cervical cancer, which is believed to have a causal role in all of cervical cancer cases (4). Although more than a hundred HPV types have been identified, only some types can cause cervical cancer. HPV 16 and 18 are the most common subtypes identified in cervical cancer, where they account for about 70% of cervical cancers worldwide (5). Nevertheless, cervical cancer is preventable if precancerous lesions are diagnosed early by Pap smear screening and subsequently treated. Pap smear screening remains an effective and widely used method for early detection of pre-cancer and cervical cancer. This test may also detect infections and abnormalities in the endocervix and endometrium (6).
Cervical cancer is more common among women not undergoing regular cervical cytological tests. Squamous cell carcinoma was 3.9 and 13 times more in women screened once every three and ten years, respectively, compared with those screened annually(7).
In Yemen, 8.5 million women aged 15 years or older are at risk of developing cervical cancer. It is estimated that 198 women are diagnosed with cervical cancer and 117 die from the disease each year. Cervical cancer in the country ranks as the ninth most frequent cancer among women and the tenth most frequent cancer among women aged 15-44 years (8). However, there is no effective cervical screening program for early detection of invasive cervical neoplasia and for starting appropriate management to reduce female mortality rates due to cervical cancer. This plays a risky role in the prognosis of cervical cancer.
Data on the cervical cytological abnormalities in Yemen are not available (9). Therefore, this study is the first to report on abnormal cervical Pap smear findings among Yemeni women. It aimed to determine the frequency and pattern of abnormal cervical smear findings in relation to age among women attending the University of Science and Technology Hospital (USTH), a tertiary care hospital based at Sana'a, Yemen.

Study design and categorization of smear findings
This study is a retrospective, cross-sectional study. Records of women examined by conventional Pap smears in the Histopathology Laboratory of the USTH over a 4-year period (from January 2013 to December 2016) were retrieved and analyzed for abnormalities according to The Bethesda System (TBS) (10).
Unsatisfactory cytology reports were excluded. The included smears were those with very few epithelial cells or where the morphology of the cells was obscured by blood or severe inflammation according to the guidelines of TBS (10). The following categories were used: negative for intraepithelial lesions or malignancy (NILM), atypical squamous cells of undetermined significance (ASCUS), ASCUS results with possible HSIL (ASC-H), low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs) and atypical glandular cells (AGCs) and carcinomas.

Statistical analysis
Data were analyzed using the IBM SPSS Statistics, version 21.0 (IBM Corp., Chicago, IL, USA). Descriptive statistics were presented as frequencies, percentages or means ± standard deviations. Chi-square test was used to determine significant differences between the proportions of age groups, where two-tailed P value <0.05 was considered statistically significant.

Results
Of 688 cases, 599 satisfactory cases (87%) were analyzed and 89 cases (13 %) with unsatisfactory reports were excluded. The average age of the 599 satisfactory cases was 39.2 ± 10.2, ranging from 19 to 75 years. However, the age of cases with epithelial cell abnormalities was between 22 and 71 years, with the mean age being 43.11 years±11.12. As shown in Table (1), the majority of women screened by Pap smear for cervical cancer were in the age group of 30-39 years, followed by those belonging to the 40-49 age groups, while those aged ≥60 years were the least frequent. Table (2) shows that the epithelial cell abnormalities (ECAs) were found in 7.8% (47/599) of cases, which were distributed as follows: ASCUS in 4.5% (27/599) of cases followed by AGC (2.2; 13/599) and LSIL (0.5%; 3/599). However, ASCH and HSIL abnormalities were equally observed among 0.3% (2/599) of cases each. On the other hand, Figure (1) shows that ASCUS was the most frequent type of ECAs (57.4%/ 27/47) followed by AGC (27.7%; 13/47) and LSIL (6.4%; 3/47), while ASCH and HSIL were the least frequent ECAs among Yemeni patients.
The significantly higher prevalence of ECA among women aged 40 years and older in our study is in agreement with previous studies that found a relationship between age and ECA (24,25).
In the present study, ASCUS was the most prevalent ECA type (57.4%), and this is in accordance with the findings of many other studies in Arab (11-13, 18-20, 23) and non-Arab countries (24,(26)(27)(28)(29) On the other hand, the current study revealed that AGCs are not uncommon in Yemeni women since they represent about one-third of all ECAs among studied women. This finding is consistent with the majority of studies in the Arab region (13,(18)(19)(20)(21)(22)(23). Moreover, because cytology-based screening has a relatively lower sensitivity for the detection of early glandular lesions than for the squamouscell cancer precursors (30), the prevalence rate of AGC is expected to be higher than what was found in our study.
The high prevalence of AGC in our study requires attention and further studies because of its clinical importance as the percentage of cases associated with an underlying high-grade disease is higher than for ASCUS (10). According to follow-up studies, high-grade lesions (either squamous or glandular) may be seen in 10-39% of such cases (10).
In a study on the trend of the cellular changes during a period of 21 years (between 1992 and 2012) in Kuwait, Kapila et al. (13) noted a significant increase in the number of glandular changes. On the other hand, a recent study in Saudi Arabia stressed the need to focus more on glandular abnormalities (15).
Several studies reported increasing rates of adenocarcinoma among younger women, particularly under the age of 40 (31)(32)(33)(34)(35). This is in accordance with the finding of the present study that AGC affects both of women younger than 40 years and older. However, there was no statistically significant difference according to age.
Regarding the HSIL that has emerged as the central purpose of cervical cytology screening (10), the frequency in the present study was 0.3%. This frequency is one of the lowest frequencies in the Arab region and the world. In Arab countries, it was 5% in Iraq (21), 1.0% in Kuwait (13), 0.7-0.9% in Saudi Arabia (14,16,19,22), and 0.8% in the United Arab Emirates (11,12). However, in non-Arab counties, it was 1.8% in Bangladesh (25) and 1. 9% in South Africa (27). Since HSIL is associated with HPV persistence and higher risk for progression (10), the low prevalence of HSIL in our study may suggest that the existence of squamous lesions caused by HPV is not common in our population.
This study is limited by being hospitalbased among women referred for screening based on a gynecological indication. Therefore, the results may not reflect the true estimates of abnormal cytological findings among Yemeni women in all parts of the country.

Conclusions
Cytological cervical abnormalities are relatively common among women in Yemen. The AGCs are more prevalent than squamous intraepithelial lesions, affecting women of different ages. This requires more attention and training of physicians to master good sampling, preparation and diagnosis with a focus on glandular changes.