Conventional pap’s test and liquid-based cytology for the screening of cervical cancer with back up colposcopy directed biopsy

Abstract

The aim of this study was to screen the suspected cervical cancer patients (n=100) by liquid-based cytology and conventional pap’s smear followed by colposcopic biopsy from July 2016 to June 2017. In conventional pap’s test, 73 cases were true negative whereas 25 cases were false negative. However, in liquid-based cytology, 68 cases were true negative and 23 cases were false negative. Finally when colposcopic examinations were done, 61 cases were true negative and 15 cases were false negative. The sensitivity of liquid-based cytology was 11.5% for cervical cancer screening which was more than the conventional pap’s smear (3.8%). In conclusion, liquid-based cytology should be more preferable method than the than conventional pap’s smear for the diagnosis of precancerous lesion of the cervix.

Introduction

Cervical cancer is the second most common causes of death in gynecological cancer of women.¹ For the last 60 years, the mainstay of cervical cancer screening is Papanicolaou test (pap test). It involves the examination of exfoliating cells from the transformation zone and detects cancerous or precancerous lesion. The test can be performed by traditional method or liquid-based cytology. In liquid-based cytology, collected cells are released into a vial of liquid preservative that is then used for microscopic evaluation of the cells. Traditional pap test involves direct transfer of the cervical cells to a microscope slide for evaluation. When abnormal cells are detected on the pap test, colposcopy is indicated.²

The traditional pap's smear has a significant false negative rate of 15 to 40% where absolute sensitivity for CIN (cervical intraepithelial neoplasia) II-III is 50-89%.^4-6 The main factors for false negative rate are:specimen collection, smear formation, false error, deficiency of consistent sufficient number of cytotechnician.

There are two limitations of pap’s smear which are false negative result and cost of the test.

Anyway, it is called primary gold standard screening test for cervical cancer due to higher specificity (98.6%).⁷

Liquid-based cytology has been associated with the reduction of unsatisfactory rate.⁸ It has been suggested that the sensitivity of liquid-based cytology for the detection of CIN I-II is same as conventional cytology but its sensitivity for detection of CIN II-III is lower. Comparative performance of liquid-based cytology has suggested that sensitivity for detection of CIN II-III is similar to that of conventional cytology but specificity is lower.⁹Another study showed that liquid-based cytology does perform better than conventional cytology in term of positive predictive value for detection of CIN -II or CIN-III.¹⁰ Liquid-based cytology is found to be cost effective¹¹ and this test is important for detection of HPV-DNA testing. It is known that screening test has a higher sensitivity but conventional pap’s test has long been known for its low sensitivity because of inadequate sample collection and interpretation difficulties.¹² Liquid-based cytology has been well documented for its higher sensitivity.^13-15

Materials and Methods

This cross-sectional study was done at the department from July 2016 to June 2017. A total of 100 cases of women of reproductive age between 20-50 years with normal cervix were included in this study. Purposive sampling method was used to select the participants to collect data and information. A self-administered structured questionnaire was used to collect data. The purpose of the study was explained to all respondents who fulfilled the enrollment criteria.

Statistical analysis

The pre-designed data sheet was scrutinized to check the quality of the raw data. After cross-checking, coding was developed for each and every question. The variable was defined for a single observation with the value and value description was done according to the data type. After editing and coding, the coded data were analyzed by using SPSS 20.0 version.

Results

Results were compiled and manually analyzed. Total number of patients were 100. Among them 44% of patients were in the age range of 30-39 years. 28% were between 40-49 years, 12% were less than 30 years and 16% of patients were more than 49 years.

Regarding the report of cervical cancer screening tests, conventional pap’s test, liquid based cytology, colposcopic guided biopsy were done from 100 patients (Table I). The results of the conventional cytology was negative for CIN (98%) and ASCUS (atypical squamous cell of undetermined significan-ce) (2%). In liquid-based cytology, negative for CIN was 91% and positive for CIN was 9%. In colposcopic biopsy, CIN positive cases were 24. In conventional pap’s test, it was observed true positive 1 case, false positive 1 case, false negative 25 cases and true negative 73 cases. In liquid based cytology, true positive 3 cases, false positive 6 cases, false negative 23 cases and true negative 68 cases were observed. In colposcopic evaluation it was observed, true positive 11 cases, false positive 13 cases, false negative 15 cases and true negative 61 cases.

In this study, the sensitivity of liquid-based cytology was 11.5% for cervical cancer screening which was more than conventional pap’s smear (3.8%) (Table II).

Discussion

This study showed positive for CIN 9% by liquid-based cytology which was more than conventional pap’s test (2%). On the other hand, CIN was positive in 24 cases by colposcopic biopsy in 100 patients. In this study, the sensitivity of liquid-based cytology was 11.5% for cervical cancer screening which was more than conventional pap’s smear (3.8%).

Liquid-based cytology increases the detection rate of low grade squamous intraepithelial lesion and high grade squamous intraepithelial lesion by 47 and 116% respectively compared with conventional pap’s test which is correlated with this study.¹⁶ A study reported similar results that liquid-based cytology test increases the detection rate of atypical squamous cell of undetermined significance, low grade squamous intraepithelial lesion and high grade squamous intraepithelial lesion cytology by 75.7, 107.3 and 64.5% respectively.¹⁷ Another study showed high grade squamous intraepithelial lesion was more found in liquid-based cytology than conventional pap’s smear.¹⁸ Abnormal cytology was more by colposcopy and biopsy than other two screening procedure. So, the compliance of colposcopic procedure was higher compare to conventional pap’s smear and liquid-based cytology.¹⁹ The detection of intraepithelial lesion and cervical screening was advanced by using liquid-based cytology which was reported in another study.²⁰ In Japan, one study showed that the rate of high diagnosis of cervical cancer was more by liquid-based cytology.^21-24. Liquid-based cytology proved to be a superior screening test to detect epithelial cell abnormality due to its higher sensitivity and positive predictive value which was reported by Vassilkos et al. (2000).²⁵ A study showed that the sensitivity was significantly greater in liquid-based cytology compared to the conventional cytology (96 vs 92%) which is consistent with this study.²⁶ Another study also showed that in liquid-based cytology as a screening procedure of cervical cancer, sensitivity is greater (81.4%) than conventional paps test.²⁷

The reasons for better findings of pre-invasive lesion of cervix by liquid-based cytology are: a) collection of sample is simple and technically easy and nondoctor can easily collect the sample, b) the smear made from sediment which contains undamaged healthy cell, c) smear is not contaminated by the necrosed cell, debris, blood or mucus. So, the detection of abnormal cells became easier, d) autosomal cytological examination give low false results.

Conclusion

Liquid-based cytology is better than the conventional pap’s test as a screening procedure of cervical cancer which can be confirmed by colposcopic guided biopsy.

Ethical Issue

The research protocol was approved by the ethical review committee of BSMMU before starting this study. Informed consent was taken from all participants.

Conflict of interest

There is no conflict of interest with any person or group or agency about this work.

Ethical Issue

The ethical approval of the study was taken from the Institutional Review Board of Bangabandhu Sheikh Mujib Medical University.

Acknowledgement

We are grateful to the Pro-Vice Chancellor (Research and Development) of Bangabandhu Sheikh Mujib Medical University for granting the financial support to run this project.

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