Pattern of Pap smear Cytology and Its Histopathological Correlation at a Tertiary Care Center

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1 Research Article Rohan Gupta 1, SG Gupta 2, KB Mishra 3, Roma l Singh 4 1 Resident Doctor, 2 Professor, 3 Professor and HOD, 4 Assistant Professor, Department of Pathology, L.N. Medical College, Bhopal, M.P. India. Correspondence to: Dr. Rohan Gupta, Department of Pathology, L.N. Medical College, Bhopal, M.P. India. Id: Pattern of Pap smear Cytology and Its Histopathological Correlation at a Tertiary Care Center Abstract Background: Cancer cervix is a leading cause of mortality and morbidity in developing countries like India. Developing countries accounted for about 80% of the global burden. This study was conducted to highlight the importance of Pap smear in differentiating premalignant and malignant lesions as well as to clinically correlate to analyze sensitivity, specificity, and positive predictive value for Pap smear. Materials and Methods: This cross-sectional study of 500 cervical Pap smears performed, with cyto-histo correlation was done on 130 women with age group 20 to 75 years coming to the cytology and histology section of pathology department, L.N. Medical College and Research Centre, Bhopal, during the time period of 1st Jan 2015 to 31st Dec All the smears were reported as per the 2014 Bethesda system. Results and Conclusion: Cervix with discharge and bleeding was found to be a common symptom in cervical lesion with other findings of vaginal burning and itching for which Pap smear test was done which was found to be in agreement with sensitive and specificity to histopathological examination for the early detection of different cervical lesions as well as for malignancy with concordance of 75% for normal and infection and 55.5% for CIN1, 100% for CIN 2, 3 and 100% for malignant cases. Out of 500 cases, maximum cases of Pap were negative for intraepithelial lesion or malignancy 377cases (75.4%) followed by low-grade squamous intraepithelial lesion with 37 (cases (7.4%) (followed by high-grade squamous intraepithelial lesion with 6 cases (1.2%) then and minimum number of carcinoma cases 04 (0.8%-including 0.6% of squamous cell carcinoma and 0.2% of adenocarcinoma). Keywords: Pap smear, Cervical cancer, Cervical intraepithelial neoplasia, The Bethesda system. Introduction How to cite this article: Gupta R, Gupta SG, Mishra KB et al. Pattern of Pap Smear Cytology and Its Histopathological Correlation at a Tertiary Care Center. Rec Adv Path Lab Med 2016; 2(2): ISSN: The Papanicolaou (Pap) smear was introduced in 1941 and became the standard screening test for cervical cancer and premalignant lesions. 1 Cervical cancer is the most common cancer among women after breast and colorectal cancer in the world, but in developing countries like India it is the leading cause of mortality and morbidity. Women in these countries usually present to the clinic only when they have symptoms, such as pain, discharge, and/ or abnormal bleeding. 2 Nearly 4 lakh new cases of cervical cancer are diagnosed annually worldwide and 80% of them are diagnosed in the developing countries. 3 Cervical cancers can be prevented through early detection by means of effective screening techniques. Cervical Pap smear is a sensitive test for early screening of the cervical lesion. Though Pap smear is just a routine screening test, the overall sensitivity in detection of premalignant lesions like high-grade squamous intraepithelial lesion (HSIL) is 70-80% and has been proved very effective in differentiating between inflammatory, premalignant and malignant lesions. 4,5 Thus, epithelial changes can be treated, preventing cervical cancer. 6,7 ADR Journals All Rights Reserved.

2 Gupta R et al. Rec. Adv. Path. Lab. Med. 2016; 2(2) In 1988, The Bethesda System (TBS) of terminology was introduced to sub-classify the lesions into high-grade and low-grade squamous intraepithelial lesions (SIL) for Pap smear reporting and some studies reported comparison of various terminologies. 8,9 Recently, TBS 2014 for reporting the results of cervical cytology was developed with introduction of some newer terminology that could provide clear guidance for clinical management. 10 Pap smear is a screening test only. Positive test requires further investigation like colposcopy, cervical biopsy and fractional curettage. Pap smear can detect 70-95% of cancer of the cervix and about 70% of endometrial cancer shown in different studies. 11 Reliability of the report depends upon the slide preparation and skill of cytology. Whereas single test yields as much as 10-15% false negative reading, it is reduced to only 1% with repeated tests. Diagnosis can only be made for certain by microscopic examination of cervical tissue. Biopsy is essential in every case where signs or symptoms raise the slightest suspicion and it is irrespective of whether cervical smear contains malignant cells. Either punch or wedge or cone biopsy can be taken depending upon lesion and involvement. Keeping the above facts in view, the present study is designed to evaluate the role of Pap smear and biopsy in a woman presenting with unhealthy cervix as well as to determine the accuracy of Pap test by correlating with histopathology for clinical compare, evaluate sensitivity, specificity, and positive predictive value. Materials and Methods This is a prospective study of 500 cervical Pap smears performed with cyto-histo correlation done on 130 of women with age group 20 to 75 years coming to the cytology and histology section of pathology department, L.N. Medical College and Research Centre, Bhopal, during the time period of 1 st Jan 2015 to 31 st Dec All the smears were reported as per the 2014 Bethesda system. Methodology All females who attended Gynecology OPD in tertiary care were included in the study that satisfied exclusion and inclusion criteria. After taking informed consent, and detailed history on the standard proforma, they were enrolled in the study. Cytology smears taken by gynecology were stained using Pap stain method and any cervical biopsy specimens or hysterectomy specimens received in department of pathology for histopathological examination of above patients were fixed in 10% formalin. Tissue was processed routinely followed by paraffin embedding. Tissue sections of 4-5 µm in thickness were taken and stained with H&E stain. The Pap smears were interpreted in the department of pathology according to Bethesda system (TBS) 2014 and for histology WHO classification were used. 12 Statistical analysis was carried out by for calculating sensitivity, specificity and positive and negative predictive value (NPV) of PAP smear, colposcopy, and histopathological examination. Inclusion Criteria Women of age between 18 and 65 years. Women with symptoms like vaginal discharge, postcoital bleeding, postmenopausal bleeding, intermenstrual bleeding and persistent leucorrhoea not responding to antibiotics. Exclusion Criteria Between below 18 and above 85 years of female cases where diagnosis were known, cases undergoing chemotherapy or radiotherapy. Those who are not willing to give consent for study. Pregnant women, excessive vaginal bleeding at the time of examination. Sample Size 500 (for sample size calculation, taking prevalence of abnormal cytology 70% taking 99% confidence interval and taking precision of 5%, sample size is calculated to be approximately 500). ISSN:

3 Rec. Adv. Path. Lab. Med. 2016; 2(2) Gupta R et al. Result Table 1.Cytological Diagnostic Categories (n=500) S. No. Diagnosis No. of cases Percentage 1 Unsatisfactory for evaluation Negative for intra epithelial lesion or malignancy (NILM) ASCUS LSIL HSIL Squamous cells carcinoma (SCC) AGCUS Adenocarcinoma Total Of 500 Pap smear examined during one year period from which maximum number of cases were NILM, i.e., 377 (75.4%) which more than the three-fourth of all cases followed by ASCUS 40 (8.0%) then LSIL 37 (7.4%) Table 2.Chart depicting Clinical Symptoms and HSIL 06 (1.2%) cancer incidence found to be 0.8% (n=4). Precursor lesion (intraepithelial lesion) found to be 8.6% (n=43). Rate of epithelial cell abnormality is 17.8% (n=89). In Table 2, depicting clinical symptoms corresponds to most common symptom of unhealthy cervix is discharge per vaginum and higher lesion is associated with bleeding and vaginal burning. Table 3.Age-Wise Distribution of Total Number of Patients S. No. Age group (Years) Number of Cases Percentage > Table 4.Age-Wise Abnormal Findings Age No. of ASCUS LSIL HSIL SCC AGCUS Adeno Total No. of Percentage Group Cases Carcinoma Abnormal Findings > Total ISSN:

4 Gupta R et al. Rec. Adv. Path. Lab. Med. 2016; 2(2) In Tables 3 and 4, correspond to age-wise and abnormal cytological finding in different age group is shown, according to which maximum number of cases were recorded in age group of (34.6%) years of which Histology cytology Number of Cases for Histology 41 were abnormal with two malignancies followed by (34.0) years, of which 25 abnormal finding were noted with no malignancy. As age increases, chances of malignancy also increase. Table 5.Cyto-Histo Correlation Normal Including CIN1 CIN 2,3 SCC Papillary Infection (LSIL) (HSIL) Sq Transitional Ca NILM ASCUS LSIL HSIL SCC AGCUS 1 1 ADENO. Ca 1 1 Total Cyto-histo correlation is shown in Table 5, Sample (n=130) available for histological correlation, according to Bethesda 2014 classification LSIL cytology diagnostic category histologically equivalent to HPV/ mild dysplasia/ CIN1; similarly HSIL category histologically equivalent to moderate and severe dysplasia, CIN2, CIN 3, CIS and with feature suspicious for invasion. Table 6.Statistical Value of Pap Smear for Different Grades of Disease (%) Normal including infection CIN1 CIN 2,3 Carcinoma Sensitivity Specificity PPV NPV Accuracy Concordance rate for different lesion was calculated and is given below. Table 7.Concordance rate for different lesions Histological Diagnosis Concordance rate (%) Normal and inflection 75 CIN CIN 2, Malignancy 100 In Table 6, different statistical values of Pap smear were shown for different lesions; the diagnostic accuracy was almost 100% for HSIL and for malignancy, the PPV value for premalignant lesion was 85% and for carcinoma 100%, over all sensitivity and specificity was good for malignant and premalignant lesion, Pap smear was less sensitive in low-grade lesion CIN1, i.e., 55% but has high value in specificity (100%), with moderate diagnostic accuracy The overall statistical values of Pap smear for dysplastic and premalignant condition were sensitivity 67.27%, specificity 92%, positive predictive value 86%, negative predictive value 79%, and diagnostic accuracy 81%. Discussion Cancer cervix is considered to be an ideal gynecological malignancy for screening as it meets both test and disease criteria for screening. These cervical lesions progress with time and ultimately end up as frank invasive cancer where 4% reach the invasive stage by end of one year and 11% by end of 3 years; as much as 22% become invasive by 5 years and 30% by 10 years. 13 It has a long latent phase during which it can be detected as identifiable and treatable premalignant lesion which precedes the invasive disease and the benefit of conducting screening for carcinoma cervix exceeds the cost involved. 14 ISSN:

5 Rec. Adv. Path. Lab. Med. 2016; 2(2) Gupta R et al. In the present study, the maximum number of cases were in the age group of years (34%), similarly reported by Sharma et al. 15 and by Algotar et al. 16 In a study of Goyal et al. 17 the mean age was years. Women aged 45 years or above harbor the bulk of premalignant and malignant lesion. In the present study, white discharge per vaginum (40%) was the most common complaint similarly reported by Chaudhary et al., 18 39%, followed by irregular bleeding in 25% of the patients. Patients with cancer also presented with post-coital bleeding and in cases of older age group, post-menopausal bleeding was seen. In this study, 75% patients had the cytological diagnosis of benign/ inflammatory and carcinoma was present in 0.8% of the cases. This is comparable to a study by Kulkarni 19 in which benign cases were 73% and carcinoma was diagnosed in 0.2% of the cases. Most common cancer in the present study was squamous cell carcinoma (0.6%). This study showed results approximate to those seen by Sunita et al. 20 The comparison with different studies is shown below. Table 8.Comparison with Other Studies Studies No. of Cases Unsatisfactory Smear % NILM % SIL % Invasive Carcinoma % Judoo and Ranade Yajima et al Beinton et al Mital et al Chauhan et al Spinilla et al Tabrizi et al Thomas et al Karuma et al Mishra & Panday Sherwani et al Kulkarni Bal et al Sunita et al Verma et al Present study In various studies, SIL rate varies from 3% to 13%, and carcinoma incidence from 0.1% to 6%. In our study, SIL rate is 8.6% and carcinoma incidence is 0.8% as compared to other studies. Cyto-Histo Correlation On comparison with other studies, the following results were obtained: Table 9.Comparison of Present Study with Other Studies Study Sensitivity (%) Specificity (%) PPV (%) NPV (%) Joshi et al Chaudhary et al Ashmita et al Mallur et al Pimple et al Goyal et al Albert et al % 100% Bukhari MH et al % 100% Present study In Table 9, the present study was compared with other studies with respect to statistical value of sensitivity, specificity, PPV and NPV. This study shows that Pap smear has less sensitivity because it is associated with high false negative result but has high specificity rate. The sensitivity of Pap smear can be increased by eliminating high false negative results by proper technique of slide preparation, fixation and interpretation and when it is used in adjunct to other screening tools like VIA or colposcopy. 17 ISSN:

6 Gupta R et al. Rec. Adv. Path. Lab. Med. 2016; 2(2) Diagnostic accuracy in the present study shows accuracy of 81% in dysplastic and premalignant condition. This is in agreement with 80% in Joshi et al., in Chaudhary et al., 35 80% in Mallur et al.,.37 and also this study has accuracy of 100% for malignant cases which also coincides with finding of Nawaz et al. 41. Conclusion Cervical cancer is one of the most common malignancies in women of developing countries like India. The incidence of cervical cancer has been reduced significantly over the decades after the starting of mass screening programs and awareness campaigns promoting Pap smear as an effective tool for early detection of premalignant and malignant lesions of cervix when it is amenable to simple cure and treatment. Present research confirmed its excellent sensitivity, specificity and PPV in high-grade lesion and carcinoma. Relatively low CIN sensitivity can be improved by adequate sampling and avoiding technical error and Bethesda system is strongly recommended for adequacy of sampling to minimize inconsistency. Conflict of Interest: None References 1. Papanicolaou GN, Traut HF. The diagnostic value of vaginal smears in carcinoma of the uterus. Am J Obstet Gynecol 1941; 42: Patel MM, Pandya AN, Modi J. Cervical Pap smear study and its utility in cancer screening, to specify the strategy for cervical cancer control. National Journal of Community Medicine 2011; 2(1). 3. Khan MS, Raja FY, Ishfaq G et al. Pap smear Screening for Precancerous conditions of the cervical cancers. Pak J Med Res 2005; 44(3): The 2001 Bethesda System. Terminology for reporting results of cervical cytology. JMA 2002; 287: Maryem A, Ghazala M, Arif HA et al. Smear pattern and spectrum of premalignant and malignant cervical epithelial lesions in postmenopausal Indian women: A hospital based study. Diagnostic Cytopathology 2011; 40(11): Jonathan SB. Berek and Novak s Gynaecology. 14 th Edn. Philadelphia: Lippincott William Wilkins, 2006: Leopold K. The New Bethesda system for reporting results of smears of uterine cervix. Journal of National Cancer Institute 1990; 82(12): Richart RM. A modified terminology for cervical intraepithelial neoplasia. Obst Gynecol 1990; 75: Pradhan B, Pradhan SB, Mital VP. Correlation of Pap smear findings with clinical findings and cervical biopsy. Kathmandu University Medical Journal 2007; 5(4): Nandakumar A, Ramnath T, Chaturvedi M. The magnitude of cancer cervix in India. Indian J Med Res 2009; 130(3): World Health Organization. WHO guidelines for screening and treatment of precancerous. Available from: _eng.pdf. 13. Padubidri VG, Daftary SN. Shaw s textbook of Gynaecology. 14 th Edn. Chapter 29. Elser, 2008: Kerkar RA, Kulkarni YV. Screening for cervical cancer: An overview. J Obstet Gynecol India 2006; 56: Benedet JL, Boyes DA, Nichols TM et al. Colposcopic evaluation of patients with abnormal cervical cytology. Obstetrical & Gynecological Survey 1976; 31(11): Algotar K, Nalwade A, Sachdev S. Predictive value of colposcopy in cervical cancer screening. Bombay Hosp J 2004; 4603: Goyal S, Tandon P, Bhutani N et al. To study the role of visual inspection of cervix with acetic acid (VIA) in cervical cancer screening. Int J Reprod Contracept Obstet Gynecol 2014; 3: Chaudhary RD, Inamdar SA, Hari Haran C. Correlation of diagnostic efficacy of unhealthy cervix by cytology, colposcopy and histopathology in women of rural areas. Int J Reprod Contracept Obstet Gynecol 2014; 3: Kulkarni AM. Pattern of epithelial cell abnormalities in Pap smear According to Bethesda System in South Western Maharastra. Indian Obstretics & Gynaecology 2014; 4(2). 20. Bamanikar SA, Baravkar DS, Chandanwale SS et al. Study of cervical pap smears in a tertiary hospital. Indian Medical Gazette Jul Jajoo K, Ranade C. A critical review of cases of cervical erosion. J of Obst and Gynecol 1979; 42: Yajima A, Mori T, Shinji S et al. Effect of cytological screening on the detection of cervical carcinoma. J of Obst and Gynecol 1982; 59(5): Beinton A, Palintasa, Conner B. Estrogen depressive symptoms in postmenopausal women. J of Obst and Gynecol 1986; 80(1): ISSN:

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