Frequency of Cervical Pre-Malignancy in Pregnant Women

The abnormal growth of precancerous cells on the surface of the cervix is cervical intraepithelial neoplasia (CIN). Cervical intraepithelial neoplasia is classified according to extent of the abnormal cell growth and is classified as low grade and high grade. Human papilloma virus, a sexually transmitted virus is commonly associated with CIN. A regular Pap smear test can detect CIN at early stages and this helps in treating disease at early stage and protection against human papilloma virus can be provided with vaccine. Objective: To find the frequency of cervical premalignancy in pregnant women. Patients and Methods: This cross – sectional study was conducted at Department of Obstetrics and Gynaecology, Lahore. A total of 260 patients were included in this study. Pap smear samples were collected and fixed in 95% alcohol solution. Smears were sent with a histopathology form for reporting. 1 WMO, Dept of Obstetrics & Gynaecology Services Hospital, Lahore. 2 Assistant Professor of Obstetrics & Gynaecology KEMU / Lady Aitchison Hospital, Lahore 3 Associate Professor of Obstetrics & Gynaecology FJMU / Sir Ganga Ram Hospital, Lahore 4 Department of Obstetrics & Gynaecology SIMS/Services Hospital, Lahore. Date of Submission 22-02-2016 Date of Revision Received 14-07-2016 Date of Acceptance for Publication 02-08-2016 Conflict of Interest: None Funding Source: None


Introduction
The cervical pre-malignancy is also known as cervical intraepithelial neoplasia (CIN).CIN is defined as abnormal growth of squamous cells and premalignant transformation on the surface of the cervix.Abnormal cellular proliferation, abnormal epithelial maturation and cytological atypia are characteristics of CIN.CIN is mainly categorized into three types according to the extent of abnormal cell.i.e.CIN I, CIN II and CIN III.Early changes in the cervix which might become cancer can be detected with screening tool known as Pap smear.Pap smear can also detect early stages of cervical cancer which is usually asymptomatic. 1ollowing are the risk factors for cervical cancer: multiparity, smoking, age at first intercourse, socioeconomic status, oral contraceptive pills (OCP) usage, and human papillomavirus (HPV) infection. 2There are various types of HPV out of which 16 and 18 are consider being high risk and associated with CIN and cervical cancer, a sexually transmitted infection accounting for 60% of HPV positive invasive cervical cancers.Body's immune system takes almost 8 -14 months to clear most cases approximately 80% of HPV.90% of the most common type of cervical cancer can be prevented with regular Pap smear every three yearly. 3n one study conducted in total 76 pregnant females Pap smear were taken and 21 % showed CIN. 4 In another study, conducted at Karachi, Pakistan, cervical smear was taken in 20,995 cervical smears taken in the obstetrics and gynaecological clinics showed 0.71% atypia.5 Another study conducted in India in which 300 pap smears were taken from patients who attended obstetrics and gynaecology showed cervical epithelial abnormalities in 5% of cases.6 Every three yearly Pap smear is recommended in women aged 18 to 69 years, who have ever been sexually active.Pregnant females should be counseled that properly collected Pap smear during pregnancy is not hazardous, only associated problems can be spotting or minor bleeding.
Chances of progression of CIN I to CIN III is 10 -16%, CIN II to CIN III is 50% and 30% of women with CIN III would develop invasive cancer over 20 years period. 1 In case of normal result pap smear should be repeated every three yearly, repeat smear after 6 months is recommended in case of inflammatory and borderline smear result, colposcopy is advised in case of CIN I, CIN II, CIN III, in case of suspected invasion or abnormal glandular cell advise urgent colposcopy biopsy. 7he rationale of conducting this study is to improve the detection rate of cervical intraepithelial neoplasia (CIN) in reproductive age group.It is evident from literature review mentioned above that study related to antenatal population used small number i.e. 76 cases of pregnant patients that showed 21% CIN in pap smear samples. 4Similarly, studies conducted in Pakistan and India screened both obstetrics and gynaecological patients showed up to 5% of cervical epithetlial abnormalities. 5,6It means that study conducted in antenatal population showed high incidence of CIN as compared to both obstetrics and gynae patients.These studies indicated that pap smear is not taken regularly in reproductive age groups in Pakistan.In the proposed study, we took 260 pregnant women to collect the recent data of cervical pre-malignancy in reproductive age group.Cervical abnormalities usually occurs in reproductive age group, therefore when females are pregnant they mostly attend hospital and are concerned about their health and this is a time to offer them cervical screening.Moreover, screening for cancer of the cervix remains a neglected health care issue in Pakistan.Hence, every pregnant female who did not have Pap smear in last three years should be offered pap smear during antenatal period.

Patients and Methods
It is a crosssectional study conducted in Department of Obstetrics and Gynaecology, Lahore.Study was carried out over a period of six months.Sample size estimated using 95% confi-dence level with 5% margin of error with an expected percentage of cervical pre-malignancy i.e. 21% in pre-gnant women is 260. 4 Pregnant women who never have pap smear in last three years were included and following women were excluded.Pregnant women who have negative pap smear in last three years, patients with threatened miscarriage and patients with low lying placenta.
260 pregnant patients from antenatal clinic were selected after fulfilling the inclusion and exclusion criteria.After taking informed consent, each patient underwent clinical gynecological examination followed by cervical sampling.Patient was placed in lithotomy position and cervical sample was obtained by using a spatula.Pap smear samples were collected and fixed in 95% alcohol solution.Smears were sent with a histopathology form for reporting and were reported by consultant pathologist.CIN is the potentially premalignant transformation and abnormal growth of squamous cells on the surface of the cervix CIN is characterized by abnormal cellular proliferation, abnormal epithelial maturation and cytological atypia.Mainly, it is categorized into three types i.e.CIN I, CIN II, CIN III.CIN I is Mild dysplasia, it is confirmed to the basal 1/3 of epithelium.CIN II is Moderate dysplasia, it is confirmed to this basal 2/3 of epithelium.CIN III is Severe dysplasia may span more than 2/3 of epithelium also known as carcinoma in situ.The study was submitted to hospital ethical committee for approval.Data was entered and analyzed using SPSS 17. Quantitative variables like age presented using mean and standard deviation.Qualitative variable like gender and cervical pre-malignancy (CIN I, CIN II, CIN III) was presented using frequency and percentages.Data was stratified for the variables like history of smoking, oral contraception, low socioeconomic status, multiple marriages and early marriage to address the effect of modifiers.Chi-square test was applied and p-value ≤ 0.05 was considered as significant.

Discussion
Second most common malignancy in females is cervical carcinoma and is third common cause of female mortality.500,000 new cases of cervical carcinoma are diagnosed each year and responsible for 274,000 deaths.In Europe the crude mortality rate due to cervical carcinoma is 5.9/100,000 women/year and in developing countries mortality rate due to cervical carcinoma is 10 times higher. 8Cervical intraepithelial neoplasia (CIN) is growth of abnormal cells on cervix and it is premalignant condition of the cervix. 9Screening tests for cervical cancer include Pap smear and of human papillomavirus (HPV) DNA test.If screening test shows abnormalities then next step is colposcopy and cervical biopsy which may result in a diagnosis of CIN, glandular neoplasia, or cervical cancer. 10IN is divided in to two type of lesions, low grade and high grade.Women having high grade lesion has more chances of developing cervical carcinoma as compare to women having low grade CIN.The reason of treating CIN is to prevent possible progression to cervical cancer and avoiding overtreatment of lesions that are likely to regress.These days rising incidence of CIN is noted among young women.For this reason pregnancy is high time and provides peculiar opportunity to undergo cytocolposcopic examination for those women who do not take part in a screening program for cervical carcinoma.When CIN is diagnosed during pregnancy, the question arises that whether it is better to treat the lesion or not during pregnancy.To contribute to the solution of this issue we initiated a study on the management of high-grade CIN in pregnancy. 11n present study majority of patients belonged to low socioeconomic status.8 cases of cervical premalignancy on pap smear were having low socioeconomic class.Low socioeconomic factor for developing CIN is because of poor utilization of preventive services and subsequent presentation at late stage of disease.This study is comparable to the study carried out by Engelstad et al, in which revealed that low income women all at higher risk of developing cervical cancer. 12moking is a potential risk factor for CIN because  14 For successful use of pap smear, however it is essential that patients can be screened on regular basis so that those women whose lesion have not detectable on the first smear will have such lesions detected on the next regular schedule screening examination.So that incidence as well as mortality and morbidity associated with cervical cancer could be further reduced in near future.

Conclusion
In conclusion, women having history of low socioeconomic status and oral contraceptive were more prevalent in developing CIN.It is recommended that cervical cancer screening by pap smear for all women who have been sexually active and who have cervix.For successful use of pap smear, however it is essential that patients can be screened on regular basis so that those women whose lesion have not detectable on the first smear will have such lesions detected on the next regular schedule screening examination.So that incidence as well as mortality and morbidity associated with cervical cancer could be further reduced in near future.

Table 1 :
Descriptive Statistics of Age at Marriage, Pre Malignancy and CIN Grades.

Table 2 :
Comparison of Cervical Pre-Malignancy on Pap Smear with Different Factors.

Table 1 .
13nger cells in cells of cervical epithelial tissue.Due to religious, cultural and social factors it was not surprising to note that out of 260, no one gave history of smoking.On other hand, Jubelirer et al, in 1996 reported that in screened females 40% cervical cancer has association with smoking risk.13Earlyage of marriage is also risk factor of CIN.