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ORIGINAL ARTICLE Pap smear versus visual inspection of cervix with acetic acid (VIA) for detection of cervical abnormalities
Alia Bano, Gulfishan Haq, Anila Sheikh

Abstract Objective: To evaluate the validity of visual inspection of cervix after application of acetic acid by comparing it with cervical cytology for detection of cervical abnormalities. Study design: Cross-sectional study. Setting: Out patient department of Gynae unit-I I Civil Hospital Karachi. Duration of study: Study was conducted from 1-8-2006 to 31-1-2007. Subject and method: After informed consent, 150 patients fulfilling inclusion criteria were subjected to cytology and VIA. Colposcopic examination was performed in all and on site biopsy was taken if required. Sensitivity, specificity, positive and negative predictive values were calculated by taking colposcopy and or directed biopsy as gold standard. Result: Out of 150 patients 13(8.67%) were positive on VIA and 31 were positive on Pap smear. The sensitivity of VIA was 71.4% and of Pap smear was 78.6%. Corresponding specificities were 97.8% and 92.6%. Positive predictive values were 76.9% and 52.4% while negative predictive values were 97.1% and97.7% respectively. Conclusion: These results indicate that VIA has comparable sensitivity and specificity to Pap smear. Low cost, easy applicability and immediate results make VIA a useful screening test in developing countries like Pakistan. Keywords: Cervical cancer, visual inspection of cervix with acetic acid (VIA), Pap smear, screening Introduction: Cervical cancer is the most common cancer in women in low-resource countries, it is estimated that 85% of the global cervical cancer burden of approximately 4, 93,000 cases and 2, 73,000 deaths being currently found in developing countries. 1 Slow natural history of cervical cancer led itself well to a screening programme that identifies dysplasia and prevents it from progressing to invasive carcinoma.2 An organized screening programme for detection of pre-malignant changes offers the best mean to control invasive lesions. 3 Lifetime risk for a woman to develop cervical cancer in low resource setting is 21% to 41%.4,5 Cytology based screening programmes have markedly reduced the incidence of cervical cancer in developed countries that have the infrastructure to support these programme.6,7 Cytology based screening programme require technical capabilities, trained staff personal and financial resources that are beyond the capacity of health care system in most developing world.8 In Pakistan cervical cancer is the most common malignancy of genital tract in females with the relative frequency of 8.8%.9 A study conducted at Ziauddin Medical University shows that 25% of all female malignancies were of uterine cervix.10 Another local study from Armed Forces Institute of Pathology (AFIP) shows cervical cancer in 4.2% women.11
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Dow University of Health Sciences Karachi A Bano G Haq A Sheikh Correspondence: Dr Gulfishan Haq Associate Professor, Ob-Gyn Unit III, Dow University of Health Sciences Karachi. Cell: 0300 823 7746 email: gulfishan.tariq@ yahoo.com

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explanation of procedure , all women were subjected to per-speculum examination of cervix. After direct visual inspection, cervical smear was taken by spatula, smear was immediately fixed with fixative, this was followed by application of 3% acetic acid with cotton swab and cervix was examined 60 second later under adequate light source. VIA was considered positive if definite acetowhite lesion visualized close to squamocolumnar junction (SCJ) or if entire cervix or any growth on cervix turned out to be acetowhite. Details were recorded on the proforma. Cervical smears were sent to cytopathology department of Dow University of Health sciences and cytologist was unaware of results of VIA. Reference standard for final disease status was colposcopy and every patient was subjected to it, on site biopsies were taken if required. Disease status was assessed on colposcopy and histopathology report if biopsy performed. Reference standard negative women were those who were assessed normal by colposcopy and negative on histopathology. True disease was defined as confirmed cases. Validity of visual inspection cervix was evaluated by colposcopy and biopsy of cervix if indicated. Statistical analysis was preformed through SPSS version-10.0. Frequencies and percentages were computed to present the categorical variables like short history of discharge, appearance of cervix, Pap smear findings, colposcopic findings and histological findings. Sensitivity analysis was performed to compute sensitivity, specificity, positive predictive value and negative predictive value of VIA by taking colposcopy and histopathological findings if biopsy was sent as gold standard. Results: Average age of the patients was 35.25 9.58 (Range = 20 to 60) years. Majority of the patients (65.3%) had no history of discharge but out of the rest 52 patients who reported history

Facilities for cervical cancer screening are not widely available to women in Pakistan like other developing countries.12 Therefore there is a clear need for viable, accurate and cost effective alternative screening method for control of cervical cancer in Pakistan. Direct visual inspection of cervix after application of acetic acid (VIA) had been demonstrated to detect high-grade lesion of cervix.3 Different studies suggested that VIA constitute a promising approach in low resource setting. In studies it is proved that direct visual inspection is feasible and had a superior sensitivity compared with cervical cytological analysis in detecting pre-malignant lesion of cervix and can be used as a primary screening test where cervical cytological services are sub optimal.13,14 Therefore the purpose of this study was to evaluate the validity of visual inspection of cervix with acetic acid for detection of cervical lesions in our setup so that this test can be applied in resource poor, remote areas of Pakistan where conventional screening test is not available. 80% of deaths from cervical cancer occur in women in the prime of their lives, busy with child rearing who are living in the neediest countries of the world.15, 16 Material and Methods: The study was conducted at out patient department of Gynae and Obstetrics Unit ll Civil Hospital Karachi; prospectively from 1-8-2006 till 31-1-2007. It was convenience sampling (non-probability). Patients attending outpatient department of Gynae Unit ll Civil Hospital Karachi aged 20 and above and sexually active were included, after informed consent. Women who were virgin, pregnant, menstruating, had history of hysterectomy and diagnosed case of cervical cancer were excluded from the study. It was a cross sectional study. Total 150 Patients attending outpatient department of Gynae Unit ll Civil Hospital were included in the study. Informed consent was taken and confidentiality was maintained. After
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of discharge, 40 (26.7%) reported a white color discharge followed by 9 (6%) who reported dirty discharge, 2 (1.3%) with cheesy discharge and 1 (0.7%) had history of blood stained discharge. On examination, 82 (54.7%) patients had normal appearance of cervix while ectopion was observed in 38 (25.3%), cervix was hypertrophic in 29 (19.3) and ulcer on anterior lip of cervix was observed in only one (0.7%) patient. Among 150 patients, normal Pap smear was observed in 64 (42.7%) whereas 48 (32%) showed inflammatory findings followed by ASCUS( atypical cells of undetermined significance ) in 28 (18.7%), LSIL ( low grade squamous intraepithelial lesions ) in 2 (1.3% ) and HSIL (high grade squamous intraepithelial lesions) in 1 (0.7%). Seven (7%) tests were concluded inadequate due to absence of endocervical columnar cells. 13 (8.67%) patients were VIA positive while 137 (91.33%) were negative for VIA. Colposcopic findings suspected 14 (9.3%) LSIL, 12 (8%) cases showed unsatisfactory findings on colposcopy while 124 (82.7%) were found negative. Twenty-six biopsy specimens were sent for histopathology out of which, 7 (26.9%) were normal, 7 (26.9%) were inflamed. Dysplasia-I was diagnosed in 8 (30.8%) patients, dysplasia-II in 3 (11.5%) and cancer was diagnosed in 1 (3.8%) case. When Pap smear findings are compared with the gold standard histopathology, it was found that out of those 26 cases, which underwent biopsy of cervix, 9 patients were confirmed on histopathology that yielded a sensitivity of 66.7%. Out of 14 negative cases true negative cases were 13 that yielded 92.8% specificity. Positive predictive value was 90%. While comparing Pap smear findings with colposcopy, 11 cases out of 14 positive cases on colposcopy were confirmed that yielded 78.6% sensitivity of Pap smear. Total 126 cases were true negative out of 136 negative cases that yielded
62(12.4%)

A Bano, G Haq, A Sheikh

Positive Negative

438(87.6%) Figure 1: Findings of visual inspection acetic acid (n = 500)

500

Number of patients

400 300 200 100 0 Normal Unsatisfactory LSIL

Figure 2: Findings of colposcopy (n=500)

25 20 15 10 5 0 Normal Dysplasia-I Dysplasia-II Cancer

Number of women

Histopathology

Figure 3: Findings of histopathology (n = 54) 92.6% specificity of Pap smear. However, positive predictive value was bit low (52.4%) as 21 cases were suspected positive on Pap smear. Negative predictive value was 97.7% (table-1). Total 13 patients were suspected positive on VIA out of which 10 patients were confirmed positive on colposcopy while 4 cases were false negative that yielded a sensitivity of 71.4%. However, 133 patients out of 136 were true negative that yielded a high specificity of VIA with colposcopy (97.8%). Three patients were false positive that described 76.9% positive predicPak J Surg 2013; 29(1): 46-51

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in coverage of population, follow-up, and treatment of screen positive women. It is now realized that the complexity of the different steps involved in cytologic screening contribute to its lack of success in low resource setting.18 After that different studies conducted in India and Zimbabwe also showed that results of VIA were comparable to that of Pap smear. Sankaranarayanan R et al19 undertook a randomized controlled trial of visual inspection screening, and they concluded that VIA screening, in the presence of good training and sustained quality assurance, is an effective method for preventing cervical cancer in developing countries. It now realized that the complexity of the different steps involved in cytology screening contribute to its lack of success in low resource setting. So cytology is not a viable option in many low resource countries and given resource and logistics, it is impossible at present to introduce the Pap smear to all parts of the world and in low-resource setting where cervical cancer is very common, we need a practical approach to screening and early detection. Faced with this dilemma we have to look for a cheaper yet reliable method of screening that will enable coverage of at least 70%of target population as emphasized by WHO, in order that positive impact of screening is felt. As it has been recommended in several previous studies that more studies should be done in low resource countries to evaluate the validity of VIA we have conducted this study to evaluate the results of VIA in our population, but as this study was a small hospital based study, it only reflects the disease in the women who have accessibility to tertiary care hospital. As the reference standard was applied in all participating women, whether test negative or positive, verification bias due to differential application of reference diagnostic investigation in screen positive and screen negative individuals was avoided to a large extent. Results of our study have shown that frequency

Table 1: Validity of pap smear with colposcopy (n = 150)

Pap smear Positive Positive Negative 11 (TP) 03 (FN) Colposcopy Negative 10 (FP) 126 (TN) 21 129 Total

Total 14 136 150 Key: TP = True positive, FP = False positive, FN = False negative, TN = True Negative Sensitivity = TP / (TP+FN)*100 = 78.6% Specificity = TN / (TN+FP)*100 = 92.6% PPV = TP / (TP+FP)*100 = 52.4% NPV = TN / (TN+FN)*100 = 97.7%

Table 2: Validity of visual inspection with colposcopy (n = 150)

VIA Positive Test positive Test negative 10 (TP) 04 (FN) Colposcopy Negative 03 (FP) 133 (TN) 13 137 Total

Total 14 136 150 Key: TP = True positive, FP = False positive, FN = False negative, TN = True Negative Sensitivity = TP / (TP+FN)*100 = 71.4% Specificity = TN / (TN+FP)*100 = 97.8% PPV = TP / (TP+FP)*100 = 76.9% NPV = TN / (TN+FN)*100 = 97.1%

tive value (table-2). Biopsy was performed on 26 patients. Out of 13 patients who were suspected positive on VIA, 9 patients were confirmed positive while 4 patients were false positive that yielded 69.2% positive predictive value of VIA. Three patients out of 12 positive patients were found false negative that yielded a sensitivity of 75%. Out of 14 negative cases, 10 were true negative that yielded 71.4% specificity of VIA and 76.9% negative predictive value. Discussion: Cervical cancer is the only malignancy of female genital tract, which can be prevented through organized screening programme. 4 Globally cervical cytology is the most widely used screening test for cervical cancer, and in most developed countries it is associated with substantial decrease in the burden of cervical cancer. In developing countries like Brazil, Costa Rica, Cuba, Mexico and other Latin American countries, however such screening programmes have been associated with no or minimal impact on disease burden. 17 It is partly because of poor quality of testing and programmatic deficiencies
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of inflammatory Pap smear was 38.4%, which is lower than given by previous local studies of Civil hospital and Abbasi Shaheed Hospital in which it was around 88%.20 Frequency of dysplasia (LSIL, HSIL) was 1% respectively in our study, which is comparable to a study of Agha Khan University Hospital that showed it to be 1.2%.21 Sensitivity of Pap smear in current study was 76% while specificity was 73.1%. Wide range of sensitivity and specificity has been reported for Pap smear ranged from 47% to 67 % and 60% to 95% respectively1 and result of our study is comparable to different studies conducted locally and internationally. The result of our study indicates that the sensitivity and specificity of VIA are almost comparable to that of cytology and, that visual screening test is a promising method for the early detection of cervical lesion in resource poor countries and our results are consistent with the past results of various community based studies therefore we feel that the results of this study can be replicated in a population based screening programme, a similar explanation was also given by other workers who worked in similar setting. We can also give appropriate training to our paramedical staff, lady health visitors and persons working in family planning centers so that VIA can be used as a mass screening tool, as every patient seen by these worker will be screened and referred if found screen positive to tertiary heath care center for further assessment and treatment, and this will also reduce the chance of losing screen positive patient Conclusion: In conclusion, VIA appears to be a valid screening test for detection of cervical abnormalities in comparison to Pap smear. In resource-limited settings like ours, where organized screening by cytology is difficult to practice, VIA appears to be a viable cost affective screening alternative with a reasonable sensitivity and specificity, which is comparable to that of cytology. VIA has

A Bano, G Haq, A Sheikh

an advantage over Pap smear, as it does not require a vast infrastructure and training of cyto technicians, maintaining adequate quality control and calling a woman with cytology-positive results again for colposcopy and colposcopic directed biopsy. As VIA is a real time test, biopsy and treatment can be performed in the same sitting, thus decreasing the probability of losing the patient. Reference:
1. Shastri SS, Dinshaw K, Amin G, Goswami S, Patil S, Chinoy R etal. Concurrent evaluation of visual, cytological and HPV testing methods for the early detection of cervical neoplasia in Mumbai, INDIA. Bull World Health Organ. 2005; 83:18694. 2. International Agency for Research on Cancer.PREES RELEASEN017 9; AUGUST 2007. 3. Ghaemmaghami F, Behtash N, Modares Gilani M, Mousavi A, Marjani M etal. Visual inspection with acetic acid a feasible screening test for cervical neoplasia in Iran. Int J Gynecol Cancer 2004; 14:465-9 4. Tayyeb R, Khawaja NP, Malik N. Comparison of visual inspection of cervix and Pap smear for cervical cancer screening. J Coll Physicians Surg Pak .2003; 13:201-3. 5. Goldie SJ, Grima D, Kohli M ,Wright TC,Weinstein M,FrancoE.A comprehensive natural history model for HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine. Int J Cancer. 2003; 106:896-904 6. Mandelblatt JS, Lawrence WF, Gaffikin L, Limpahayom KK, Lumbiganon P, Warakamin S etal, Cost and benefits of different strategies to screen for cervical cancer in less-developed countries. J Natl Cancer Inst. 2002; 94:1469-83. 7. Parkin DM.Global cancer statsics in the year 2000.Lancet Oncol.2001; 2:533-43. 8. Abdel-Hady ES,Esman M,Al-Gohary A,Hassan M,Farag MK,Abo-Alkheir M.Screening for cervical carcinoma using visual inspection with acetic acid.Int J Gynaecol Obst.2006;93:118-22. 9. Jaffery NA and Zaidi. SHM: Cancer in Pakistan. JPMA. 1987; 37: 178-83. 10. Rubina I, Siddiqui, Sadiqa N. Jaffery. Pattern of female genital tract malignancies at a private tertiary hospital. JPMA 1998; 48:51 11. Ahmed, M Khan, AH and Mansoor. The pattern of malignant tumor in Northern Pakistan.J.Pak. Med. Asso 1991; 41: 270-3 12. Nousheen A, Karim SA. The screening of cervical cancer by Pap smear in hospital based population. Ann Abbasi Shaheed Hosp Kar Med Dent. Coll. 2004; 9: 544-7 13. El- Shalakany A, Hassan SS, Ammar E, Ibrahim MA, Salam MA, Farid M. Direct visual inspection of cervix for detection of pre-malignant lesions J Low Genit Tract Dis 2004; 8:16-20. 14. Elit L, Baigal G, Tan J, Munkhtaivan A. Assessment of 2 cervical screening methods in Mongolia: cervical cytology and visual inspection with acetic acid. J Low Genit Tract Dis. 2006; 10:83-8. 15. Doh AS, Nkela NN, Achu P, Essimbi F, Essame O, Nkegoum B. Visual inspection with acetic acid and cytology as screening methods for cervical lesion in Cameron. Int J Gynaecol Obstet 2005; 89:167-73. 16. JHPIEGO News Release. Global meeting identifies cost-effective, innovative approaches to cervical cancer prevention in low resource areas. December 2005. [Cited on 2007 Oct 02].Available from URL http://www.jhpiego.org/media/release/nr 20030328.htm. Pak J Surg 2013; 29(1): 46-51

Pap smear versus visual inspection of cervix with acetic acid (VIA) for detection of cervical abnormalities 17. Sankaranarayanan R, Budukh AM, Rajkumar R, Effective screening programme for cervical cancer screening in low and middle income developing countries. Bull world Health organ 2001; 79: 954-62. 18. Basu PS, Sankaranarayanan R, Mandal R, Roy C, Das P, Choudhury D etal. Visual inspection with acetic acid and cytology in the early detection of cervical neoplasia in Kolkata, India.Int J Gynecol Cancer .2003; 13:626-32. 19. Sankaranarayanan R, Rajkumar R, Esmy PO,Fayette

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JM,Shanthakumari S, Frappart L etal. Effectiveness,safety and acceptability of see and treat with cryotherapy by nurses in a cervical screening study in India. Br J Cancer.2007;96:738-43. 20. Sangwa-Lugoma G, Mahmud S, Nasr SH, Liaras J, Kayembe PK, Tozin RR et al. Visual inspection as a cervical cancer screening method in a primary health care setting in Africa. Int J Cancer.2006; 119:1389-95. 21. Khan A, Soomro N, Bibi A. Screening of cervical cancer: cytology or visual inspection. Medical Channel.2001; 7:1-3.

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