Cervical Cancer Screening with Cytology and Colposcopy in Rural Medical College Hospital of Himachal Pradesh, India

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1 Ashok Verma et al ORIGINAL ARTICLE /jp-journals Cervical Cancer Screening with Cytology and Colposcopy in Rural Medical College Hospital of Himachal Pradesh, India 1 Ashok Verma, 2 Amrita Singhal, Suresh Verma ABSTRACT Background: Cervical cancer is the most common cause of cancer-related death among women in developing coun tries. An attempt was made to know the impact of cancer screening programs in place since 1975 in India, and to do cervical cancer screening in symptomatic women atten ding gynecology outpatient department (OPD) by a combination of cytology and colposcopy. Materials and methods: A total of 200 women in the age group of 21 to 65 years who attended gynecology OPD who consented to participate were screened by Pap smear testing and colposcopy. Women who were pregnant, and known or treated case of cancer cervix were excluded from the study. Pap smears were made with conventional method and colposcopy was done. Women were treated simultaneously with cryocautery. Results: None of the women had Pap smear testing in their life earlier suggesting need for an organized screening program. Mean age was 8.6 years. Sensitivity and specificity of Pap smear for diagnosis of low-grade squamous intraepithelial lesion (LSIL) was 76.9 and 96.2% while that for the diagnosis of high-grade squamous intraepithelial lesion (HSIL) was 66.6 and 97.6% respectively. Sensitivity and specificity of colposcopy in the diagnosis of LSIL in the present study was 92. and 100% while that for diagnosis of HSIL was 50 and 100% with 100% positive predictive value (PPV) and 92.1 to 96.5% negative predictive value (NPV). When a combination of Pap smear and colposcopy was used, the overall sensitivity and specificity for diagnosis of LSIL + HSIL was 94.7 and 90.9% respectively, and PPV and NPV was 90 and 95.2%. Conclusions: The advantage of the combination of simultaneous testing with Pap smear and colposcopy lies in its strong negative predictive value, which can decrease the frequency and closeness of follow-up required in poor resource settings. The present study supports the claim to perform combined screening tests as a routine to detect maximum number of cases with accuracy. Keywords: Cervix, Colposcopy, HSIL, LSIL, Papanicolaou test. 1 Associate Professor, 2 Junior Resident, Professor 1- Department of Obstetrics and Gynecology, Dr Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh, India Corresponding Author: Ashok Verma, Associate Professor Department of Obstetrics and Gynecology, Dr Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh, India Phone: , dr.ashok_verma@yahoo.com How to cite this article: Verma A, Singhal A, Verma S. Cervical Cancer Screening with Cytology and Colposcopy in Rural Medical College Hospital of Himachal Pradesh, India. J South Asian Feder Menopause Soc 2015;(2): Source of support: The study was conducted at Dr Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh. No fund was received from any source or agency to carry out this research. Conflict of interest: None Date of submission: 12 March 2015 Date of acceptance: 17 June 2015 Date of publication: December 2015 INTRODUCTION Cervical cancer is the commonest cause of death among women in developing countries. Mortality due to cervical cancer is also an indicator of health inequalities, as 86% of all deaths due to cervical cancer are in developing, low- and middle-income countries. Every year in India, 122,844 women are diagnosed with cervical cancer and 67,477 die from the disease. 1 India has a National program for cancer since 1975, when the emphasis was on equipping premier cancer institutions. In 2010, cancer control became a part of a more comprehensive, larger program on noncommunicable disease called National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Disease and Stroke (NPCDCS). 1 In the hill state of Himachal Pradesh, cancer cervix is the major public health problem since it ranks as the number one female cancer as per the annual reports of Regional Cancer Centre, Himachal Pradesh for the last 10 years. 2 Cervical cancer has a long preclinical detection phase consisting of slowly progressing precancerous lesions, such as cervical intraepithelial neoplasia (CIN) 2 and and adenocarcinoma in situ, caused by persistent infection with one of the oncogenic types of human papilloma virus (HPV), particularly HPV 16 and 18. Currently, carcinogenic HPV testing is much more sensitive, but less specific, than cytology for prediction of subsequent risk of precancerous lesions and is not commonly used in developing countries; consequently, 44

2 Cervical Cancer Screening with Cytology and Colposcopy in Rural Medical College Hospital of Himachal Pradesh, India colposcopy remains the gold standard after suspicious cervical pathology. Keeping in view the topographical conditions and high incidence of cervical cancer, the present study is an attempt to screen women attending gynecology outpatient department (OPD) for the cervical cancer using Pap smear and colposcopy and simultaneous treatment of women with cryocautry in the same sitting awaiting cytology and histopathology report; and to know whether previous studies in this area and National Programme for Prevention and Control of Cancer could make an impact on awareness generation for cancer screening. MATERIALS AND METHODS A total of 200 symptomatic women who consented to participate were studied at Dr Rajendra Prasad Government Medical College, Kangra at Tanda, Himachal Pradesh, from 1st May 2014 to 0th April 2015 after the approval of the Institutional Ethics Committee was obtained. Inclusion Criteria All married women of >21 years attending gynecology clinic at Dr Rajendra Prasad Government Medical College, Kangra at Tanda, Himachal Pradesh, presenting with: Vaginal discharge Coital bleeding Intermenstrual bleeding Postmenopausal bleeding Multiple sexual partners Unhealthy looking cervix Lesion that bleeds on touch Smokers, and Women referred from peripheral institutions having abnormal cytology report. Exclusion Criteria Women not willing to participate in the study Known case of cancer cervix Treated cases of cancer cervix Women who were pregnant were excluded from study. All the women attending were sensitized about the screening method to detect carcinoma of cervix in preclinical stage. The women who volunteered to participate were re-informed about the Pap smear, colposcopy and biopsy and the required follow-up in case of an abnormal pap test result with the help of an information sheet and all queries answered by the investigators. Thereafter, informed consent was obtained. A detailed history was taken in all the women and that included personal information, history, and clinical examination. Pap smears were made with the conventional method according to standard medical literature. First the sample of ectocervix was taken using a wooden spatula (Ayres), the notched end of the spatula that corresponded to the contour of the cervix was rotated by 60 around the circumference of the cervical os and was immediately smeared over labeled glass slide in rotary manner and was fixed within 0 seconds before drying in 95% ethyl alcohol in Coplins jar. For endocervical cytology, endocervical brush was inserted into the endocervix until the junctions of the bristles of the brush with the end of handle were in approximation with external os. Then brush was rotated 180 (one half turn) in endocervical canal and brush then rolled on glass slide and fixed immediately in 95% ethyl alcohol and were sent to Department of Pathology for cytological examination. All the women in the study were then subjected to colposcopy in the same sitting. The cervix was inspected with the naked eye than with a colposcope (Make Mestros Y2k, Germany having magnification up to 27 and 2 green filters) at low power followed by high power. Normal saline was applied with sprayer to cleanse the cervical secretions and to see subepithelial vascular architecture under low power followed by high power. Abnormal vessels were visualized at high power using green filter. This was followed by application of freshly prepared % acetic acid with small sprayer (10 ml syringe) which helped in coagulating and clearing mucus and visualization by colposcope after waiting for 1 minute. This was followed by application of Lugol s iodine to the cervix and biopsy site were labeled graphically in Odell s graph. Cervical punch biopsy was taken in all the women with suspicious lesions. Colposcopy was considered unsatisfactory if the squamo-columnar junction was not visible completely. Endocervical curettage was done in such women. Cytology laboratory reported the examination results according to the Bethesda III classification system (2001). In Bethesda classification smears cytological abnormalities were classified under three categories: atypical squamous cells (ASC); low-grade squamous intra epithelial lesion (LSIL); and high-grade squamous intraepithelial lesion (HSIL). The ASC category was subdivided into two categories: the unknown significance category (ASC- US) and the one which high-grade cannot be excluded (ASC-H). All the women with abnormal results were advised follow-up and treatment as per the standard guidelines. Women with preinvasive lesion were treated with cryocautry at the same time awaiting cytology and histopathology report. Those with invasive cancer in early stage were treated surgically at Dr RPGMC Kangra at Tanda and those requiring radiotherapy were referred Journal of South Asian Federation of Menopause Societies, July-December 2015;(2):

3 Ashok Verma et al to the Oncology Department at Indira Gandhi Medical College, Shimla, Himachal Pradesh, India for further treatment. Statistical Analysis The data obtained was entered in the excel sheet of the Micro soft and analyzed with help of a statistical software Statistical Package for the Social Sciences (SPSS) RESULTS None of the women who participated in the study had any test for the screening of cervical cancer earlier in their life. Ten women (5%) knew that there are tests available that can detect the cancer of the cervix. As shown in Table 1, the mean age was 8.6 ± 6.29 years with 56% women in 1 to 40 years age group. All the women belonged to rural area and were poor. None included in study gave history of smoking or tobacco use in any form. In our study, 54.5% women presented with the complaint of discharge per-vaginum as shown in Table 2. On per abdominal examination, 11 women had mass abdomen. Per-speculum findings are shown in Table. On per-vaginum examination, 18 women (91.5%) had normal findings; 11 women (5.5%) had mass in uterus or adnexa, while six women (%) had cervix that bled on touch. Pap smear was done in all the 200 women. It was unsatisfactory in two women (1%) where repeat smear was taken after months and women remained in the study. The cytological reports are shown in Table 4. Table 1: Sociodemographic characteristics of the women Sociodemographic characteristics Number Percentage Age group (years) Parity distribution Nulliparous Primipara Multipara Education level Uneducated Metric Higher secondary Graduate Marital status Married Unmarried Contraception usage None Barrier Tubal ligation IUCD Others OCP Colposcopy Examination All the 200 women had colposcopic examination. In one woman (0.5%) it was unsatisfactory, where endocervical curettage was done. The findings are shown in Table 5. Cervical biopsy was taken in 41 women who had suspicious lesion on clinical examination or on colposcopy. The histopathology reports are shown in Table 6. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Pap smear and colposcopy for the detection LSIL and HSIL, is shown in Table 7. DISCUSSION Cervical cancer is on the declining trend in India according to the population-based registries; yet it conti nues to be a Table 2: Chief complaints Chief complaints Number Percentage Vaginal discharge Intermenstrual bleeding Postcoital bleeding Postmenopausal 18 9 bleeding More than one 8 4 sexual partner Referred for unhealthy looking cervix Table : Clinical findings on per-speculum examination Perspeculum Number Percentage Total Healthy looking cervix Discharge Cervical erosion Table 4: Cytology report Pap smear Number Percentage Unsatisfactory 2 1 NILM Inflammatory Other 1.5 nonspecific findings ASCUS 2 1 ASC-H 0 0 LSIL HSIL SCC 0 0 Others

4 Cervical Cancer Screening with Cytology and Colposcopy in Rural Medical College Hospital of Himachal Pradesh, India Table 5: Colposcopy examination Colposcopy Number Percentage Unsatisfactory Normal Inflammatory Leukoplakia Condyloma 2 1 Immature metaplasia Low grade lesion 12 6 and HPV High grade lesion 1.5 Invasive 0 0 carcinoma Table 6: Histopathological diagnosis on cervical biopsy Histopathology report on cervical biopsy Number Percentage LSIL Cervicitis HSIL Immature metaplasia Leukoplakia 7. Condyloma Total (n = 41) major public health problem for women in India. 2 In our study, all the women had cancer screening for the first time in their life suggesting that an effective population screening method in community settings has to be embraced to increase the detection of cervical cancer in precancerous stage. All women in our study were married for a mean duration of 16.8 years. The mean age of the participants was 8.6 ± 6.29 years. It is though that the average age of women population in study was appropriate considering the fact that the common age to develop cervical cancer is between 40 and 50 years and its precursor lesion usually occur 5 to 10 years prior. The women who started their first smear after age of 45 years might miss the chance of cancer prevention all together. In our study, cervical biopsy was taken in 20.5% women (41 women), cervicitis was reported in 29.2% (12 women) women, LSIL in 1.75% (1 women) and HSIL in 14.6% (6 women) and none of the women was found to have invasive carcinoma. In similar study, Padmini 4 et al found chronic cervicitis in 68%, mild dysplasia in 17%, moderate dysplasia in 10% and carcinoma in 5% women out of 100 cervical biopsies. Massad et al 5 in a study of human immunodeficiency virus (HIV) seronegative women observed no lesion in 47.7%, low-grade lesion in 40.7%, high-grade lesion in 11.6% women. Shanmugham et al 6 in their study on women with persistent inflammatory Pap smear observed chronic cervicitis in 20.7% women, CIN1 in 11.1%, CIN2 in 6.9% and CIN in 2.7 women. They found invasive carcinoma in 1.% women studies. Screening for cancer cervix with Pap smear is an important part of preventive healthcare of women. Sensitivity and specificity of Pap smear for diagnosis of LSIL in the present study was 76.9 and 96.2% while that for the diagnosis of HSIL was 66.6 and 97.6% respectively. In a similar study by Pimple et al 7, sensitivity was 57.4% and specificity was 99.4% for diagnosis of HSIL. Satyanarayan et al 8 observed 6.6% sensitivity for detecting CIN2 lesions and 87.5% for detecting CIN lesions on Pap smear and specificity was 98.8 % to detect CIN2 and CIN lesions. Interestingly, an inverse relationship was observed between sensitivity and specificity in all the studies done by Padmini, 4 Nayani 9 and Albert et al 10 where a low sensitivity ranging from 24. to 60% was found but had a high specificity of 94.4 to 100%. Lower sensitivity in some studies may be due to higher number of women with cervicitis, erosion and cervical hypertrophy as the neoplastic cells can be obscured by blood, inflammatory cells, or mucous especially when conventional Pap tests are used. Table 7: Sensitivity, specificity, positive and negative predictive value of cytology and colposcopy in the diagnosis of squamous intraepithelial lesion of LSIL Cytology of HSIL of LSIL Colposcopy of HSIL Sensitivity Specificity Positive predictive value Negative predictive value Cytology and colposcopy combined of LSIL and HSIL Journal of South Asian Federation of Menopause Societies, July-December 2015;(2):

5 Ashok Verma et al Sensitivity and specificity of colposcopy in the diagnosis of LSIL in the present study was 92. and 100% while that for diagnosis of HSIL was 50 and 100% with 100% PPV and 92.1 to 96.5% NPV. Malur et al 11 observed that colposcopy alone had a sensitivity of 80%, specificity of 81.54%, PPV of 66.66% and NPV of 89.% for the diagnosis of LSIL and higher lesions. Sensitivity for the diagnosis of HSIL was lower in our study. Quitrakul et al 12 observed that colposcopically directed biopsy could accurately detect HSIL or higher lesion of uterine cervix in 87.8% with sensitivity, specificity, PPV and NPV of 84.9, 100, 100 and 61% respectively and concluded that it is a reliable method to obtain pathological diagnosis in women with abnormal cervical cytological screening. When a combination of Pap smear and colposcopy was used the overall sensitivity and specificity for the diagnosis of LSIL + HSIL in our study was 94.7 and 90.9% respectively, and PPV and NPV was 90 and 95.2%. Pimple et al 7 observed that across sensitivity of 58 to 74.5%, specificity of 57.5 to 99.4%, PPV of 1.8 to 89.4% and NPV of 96 to 97.1% for the outcomes of CIN 2+ on histopathology when a combination of cytology, colposcopy with biopsy as the gold standard. Pimple et al 7 further suggested that lower specificity could still be considered acceptable if the treatment by cryotherapy, which is effective, cheap, and safe is offered and the colposcopists are skilled in recognizing the exclusion criteria of cryotherapy. High negative predictive value in our study and similar studies suggests that performing a combination of tests as a part of routine screening for cancer cervix can be useful in detecting higher number of cases accurately. CONCLUSION We found that cancer detection programs have not been able to increase the cancer screening as shown by the present study. The accuracy of Pap smear, cytology and colposcopy in the diagnosis of precancerous and cancerous lesions of cervix were good. Pap smear and colposcopy in combination had a sensitivity of 94.7% and specificity of 90.9%, NPV of 95.2% and PPV of 90% for detection of premalignant lesions. The present study supports the claim to perform combined screening tests and simultaneous treatment with cryotherapy as a routine to detect maximum number of cases with accuracy, with minimum loss of patients to follow-up in low resource settings. REFERENCES 1. Sreedevi A, Javed R, Dinesh A. Epidemiology of cervical cancer with special focus on India. Int J Women s Health 2015;7(7): Thakur A, Gupta B, Gupta A, Chauhan R. Factors for cancer cervix among rural women of a hilly state: a case-control study. Ind J Pub Health 2015;59(1): Nayir T, Okyay AR, Nizlican E, Yesilyurt H, Akbaba M, Ilhan B, Kemik A. Cervical cancer screening in an early diagnosis and screening centre in Mersin, Turkey. Asian Pac J Cancer Prev 2015;16(16): Padmini CP, Indira N, Chaitra R, Das P, Girish BC, Nanda KM, Basu SN. Cytological and colposcopic evaluation of unhealthy cervix. J Evidence based Med Healthc 2015;2(41): Massad SL, D Souza G, Darragh TM, Minkoff H, Wright R, Kassaye S, Sanchez-Keeland L, Evan CT. Accuracy of colposcopy in HIV seropositive and seronegative women with abnormal Pap tests. Gynecol Oncol 2014;15(): Shanmugham D, Vijay A, Rangaswamy T. Colposcopic evaluation of patient with persistant inflammatory Pap smear. Sch J App Med Sci 2014;2(B): Pimple SA, Amin G, Goswami S, Shastri SS. Evaluation of colposcopy vs cytology as secondary test to triage women found positive on visual inspection test. Ind J Cancer 2010; 47(): Satyanarayan L, Asthana S, Bhambani S, Sodhani P, Gupta S. A comparative study of cervical cancer screening methods in a rural community setting of North India. Ind J Cancer 2014;51(2): Nayani ZS, Hendre PC. Comparison and correlation of Pap smear with colposcopy and histopathology in evaluation of cervix. J Evol Med Dent Sci 2015;4(5): Albert S, Oguntayo OA, Samaila MOA. Comparative study of visual inspection of the cervix using acetic acid (VIA), Papanicolaou (Pap) smear in cervical cancer screening. E Cancer 2012;6(7): Malur PR, Desai BR, Dalel A, Durdi G, Sherigar B, Gupta P. Sequential screening with cytology and colposcopy in detection of cervical neoplasia. South Asian Feder Obstet Gynecol 2009;1(): Quitrakul S, Udomthavornsuk B, Chumworathayi B, Luanratanakorn S, Supoken A. Accuracy of colposcopically directed biopsy in diagnosis of cervical pathology at Srinagarind Hospital. Asian Pac J Cancer Prev 2011;12(9):