Page mackup July-14.qxd Bangladesh Journal of Medical Science Vol. 13 No. 04 October’14 454 Original article Visual Inspection with Acetic Acid (VIA) in cervical cancer screening in low resource settings Shaheen1, Sharma R2, Rashi3 Introduction: Cervical cancer is the second most common cancer in women, and 80% of these cases occur in underde- veloped countries1. It comprises 15% of the cancers diagnosed in women in underdeveloped countries. It kills approximately 270,000 women worldwide each year, with nearly 85% of those deaths occurring in resource-poor settings2. While the incidence and mortality rates of cervical cancer have declined in developed countries since the advent of successful screening programs3-5, there has been no such trend in developing countries. Screening programs were implemented in developing countries since the early 1980’s, yet have failed to reduce the mortality rates. The WHO in 2002 estimated that only 5% of women in developing countries are screened appropriately. Likely reasons for failure in screening programs include lack of funding, insufficient access in rural areas where most of the population in developing countries reside, lack of awareness/education as to need for screening, and poor follow-up. About 50% of all cancers occur in developing countries, yet only 5% of resources are spent on the fight against cancer worldwide. India accounts for one-fifth of the world burden of cervical cancer and continues to be the most common genital cancer1. In India approxi- mately, 90,000 new cases of cancer cervix occur every year. The incidence in India is 45 per one lakh women6. In developing countries as in India, alternative, low- cost and effective early diagnosis methods are needed. Visual inspection with acetic acid(VIA) is a simple and easy-to-learn method and does not require laboratory equipment. Test results are immediate after administration. VIA is an attrac- tive method for these reasons in underdeveloped countries7-9. With suspicious lesions detected, Corresponds to: Prof. R Sharma, 2/65,Vishnupuri, Aligarh, UP (India) Email: rajyashri.sharma@gmail.com Abstract: Objective: To evaluate the feasibility and validity of visual inspection of the cervix with acetic acid (VIA) for screening cervical intraepithelial neoplasia. Materials and Methods: In this study, 942 women recruited from gynecology outpatient clinic, were screened using the Papanicolaou (PAP) smear, and VIA. The sensitivity and specificity of both the screening methods were analyzed. Results: VIA was positive in 29.3%. The sensitivity of VIA (74.16%) was much higher than that of the Pap smear (47.83%). The specificity of VIA (50.00%) was lower than that of the Pap smear (74.16%), resulting in high false-positive rates for VIA. Conclusion: Visual inspection of the cervix with acetic acid is sensitive for ecto- cervical lesions. The advantage of the VIA method lies in its easy technique, low cost and high sensitivity which are important factors for determining the efficacy of any screening program in developing countries. Keywords: cervical cancer screening; Papanicolaou (PAP) smear; visual inspection of the cervix with acetic acid (VIA) 1. Dr. Shaheen, Associate Professor, Department of Obstetrics & Gynecology, JN Medical Collage, AMU, Aligarh 2. Dr. Rajyashri Sharma, Professor, Department of Obstetrics & Gynecology, JN Medical Collage, AMU, Aligarh 3. Dr. Rashi, Postgraduate, Department of Obstetrics & Gynecology, JN Medical Collage, AMU, Aligarh DOI: http://dx.doi.org/10.3329/bjms.v13i4.15019 Bangladesh Journal of Medical Science Vol. 13 No. 04 October '14. Page: 454-459 women are directed to further treatment8,10,11. Visual inspection-based approaches to cervical can- cer screening have been extensively investigated in India. The performance characteristics of unaided visual inspection (without acetic acid), also known as ‘‘downstaging’’, has been addressed in several studies12. The purpose of this study was to test the validity of VIA in cervical cancer screening (sensitivity, speci- ficity, and positive and negative predictive values) and compare it with findings from the Papanicolaou test. Material and Methods: This hospital based prospective cohort study was carried out in J N Medical College hospital at Aligarh in the out patient Department of Obstetrics and Gynecology between June 2008 and September 2010. Nine hundred forty two women with inclusion and exclusion criteria were screened for CIN and early cervical cancer. The study protocol was reviewed and approved by institutional ethical committee and informed consent was obtained from each woman. Relevant obstetric and gynecological history was obtained and record- ed. Inclusion criteria: All women exposed to early sexual life, with multi- ple sexual partners, low socioeconomic status, hav- ing history of STD’s, with foul smelling discharge and with post coital bleeding were included in the study. Exclusion criteria Unmarried women, women with frank invasive can- cer cervix, women with bleeding per vaginum, and pregnancy were excluded. All women were subjected for per speculum exam- ination to observe the size and shape of the cervix, the external os identified with pinkish squamous epithelium and reddish columnar epithelium and transformation zone. The pap smear was taken and two samples were taken one from ectocervix and other from endocervix. The pap smear slide was immediately fixed with 90% ethyl alcohol. Later, the slide was sent for cytology in the Department of Pathology, J N, Medical College Hospital, Aligarh. Pap smear reporting was done according to the Bethesda classification . After taking pap smear, the same Women were subjected to visual inspection of the cervix after application of 5% acetic acid. Using a cotton swab soaked in acetic acid was applied on cervix for one minute and then the cervix was care- fully inspected for any aceto-white lesions, particu- larly in the transformation zone. Reporting of test outcome In the study, test was reported as positive, negative and inconclusive VIA test. Positive test: Visualization of the dense acetowhite lesion with sharp margins located in the transforma- tion zone, close to squamo-coloumner junction (SCJ). Negative test: If no acetowhite lesions were observed on the cervix polyps protruding from cervix, bluish white in color, nabothian cysts which appear as button like areas as whitish area or pim- ples, dot like areas present in the endocervix which were due columnar epithelium staining with acetic acid; if there were shiny pinkish white, cloudy white or bluish white, faint patchy or doubtful lesions with ill defined, indefinite margins or irregular, ace- towhite lesions resembling geographical lesions away from the SCJ. If VIA turns out to be positive the patient was sub- jected to further investigations such as colposcopy and guided biopsy. Statistical analysis The results of visual inspection of cervix with acetic acid (VIA) were correlated with that of pap smear on the basis of sensitivity, specificity and positive and negative predictive value. Results: Of the 942 women who participated, 45.5% were 31 to 40 years of age and 38.9% were 20 -30 years; the mean (SD) age was 34.52±2 years. All (100%) were married, 53.33% were married when they were 15 years or younger, and 39.61% married between the ages of 18 and 20 years. In the observations made after the application of the acetic acid, VIA was negative in 79.7% of the women and positive in 29.3% of the women (Table 1). Similarly, 80.10% of the women had negative smear test results and 18.89% had positive smear test results. When the Papanicolaou test results were classified according to the Bethesda System, 42.89% of the women had normal smear test results, 38.22% of them had an inflammatory smear, 2.12% had Atypical Squamous Cells of Undetermined Significance (ASCUS), 0.42% had Atypical Glandular cell of Undetermind Significance (AGUS), 9.13% had Low Grade Squamous Intraepithelial Lesion (LSIL), and 7.22% had High Grade Squamous Intraepithelial Lesion (HSIL) (Table 1). Using the Papanicolaou test, the sensitivi- Visual Inspection with Acetic Acid (VIA) in cervical cancer screening 455 ty of VIA was 74.16% and specificity was 50.00%. The positive predictive value (PPV) of VIA was 47.83%, and its negative predictive value (NPV) was 75.78% (Table 2). Discussion: In our study VIA was positive in 29.30%, which is almost comparable to studies by Tayyeb et al, 28.9%9,Belinson et al13 , 27.3%, and Doh et al14, 21.7% (Table 3). In our study with VIA, results for sensitivity and specificity were 74.16%, and specificity of 50.0% which is almost comparable to studies shown in Londhe et al15 as sensitivity 72%, and specificity 54% (Table 4). Other studies were showing the sensitivity of 71% and specificity of 74% in Belinson et al13, and sensitivity of 67% and specificity of 83.0% in Denny et al16, in the Johns Hopkins' Program for International Education in Reproductive Health (JHPIEGO)11, sensitivity was 77% and specificity was 64%. Additional results from other studies are listed in more detail in Table 4. When the studies made by using acetic acid in the recent years are examined, it is seen that the sensitiv- ity of VIA is between 60% and 95.7% and its speci- ficity is between 30.4% and 98%9,17-19. Decreasing VIA specificity means a risk of increased false-positive patient ratio. For this reason, treatment may be recommended for some women who have no neoplasm or have a low-stage disease. Despite such risks, VIA is still the most cost-efficient prognostic method for the underdeveloped countries. In our study, similar to the findings of some other studies (Table 4) made in other countries, VIA sensitivity was high, as noted in the outcomes of the compar- isons of VIA and Papanicolaou test results. This finding highlights the importance of training and experience for the clinicians who are completing the visual evaluations. In our study, VIA specificity was low, as noted in the outcomes of comparing VIA with Papanicolaou test results, perhaps in part because inflammatory lesions become aceto-white. Also, several other variables affect the performance of VIA as the light source, which should be white and condensed and the training and experience of the observer. The reasons behind the VIA specificity being high or low in different researches could be the personnel completing the VIA assessment, clini- cal criteria not properly used, differences between the research populations, and women with inflam- matory conditions included in some but not all of the studies14,18,20-22 . In our study, when the VIA and Papanicolaou test results were compared, PPV (47.83%) was low and NPV (75.79%) was high, which means that when a test is negative, the women can go home reassured that she is not likely to have Shaheen, Sharma R, Rashi 456 No. % VIA Negative 666 70.7 Positive 276 29.3 Total 942 100.0 Papanicolaou Test Negative 764 81.1 Positive 178 18.9 Total 942 100.0 Bethesda System Normal 404 42.89 Inflammatory Lesions 360 58.04 AGUS 4 0.42 ASCUS 20 2.12 LSIL 86 9.13 HSIL 68 7.22 Total 942 100.0 Abbreviation: VIA, visual inspection with acetic acid. Table 1: Distribution of VIA and Papanicolaue Test Results VIA Positive Negative Total Positive 132 144 276 Negative 46 144 190 Total 178 288 464 Table 2: Sensitivity and Specificity of VIA versus Papanicolaou Test Outcome Abbreviation: NPV, negative predictive value; PPV, positive predictive value, VIA, visual inspection with acetic acid. Sensitivity: 74.16%; PPV, 47.83%; specificity, 50.00%; NPV, 75.79%. PAPANICOLAOU TEST Table 3: Results of VIA for Other Countries Author(s) (Year) VIA Positive (%) Country No. of Women Londhe et at (1997) 52.96 India 372 Ardahan et al (2011) 9.7 Turkey 350 Belinson et al (2001) 27.3 China 1977 Denny et al (2002) 18.1 Africa 2754 Tayyeb et al (2003) 28.9 Pakistan 501 Goel et al (2005) 12.5 New Delhi 400 Doh et al (2005) 21.7 Cameroon 4813 Present study (2011) 29.3 Aligarh(India) 942 a neoplastic cervical lesion; eliminating the need for follow-up visits. However, the low PPV of VIA does present the problem of many false positives, discour- aging the see-and-treat method. However, PPV is dependent on incidence and if a see-and-treat method were implemented in a high-risk population with a high incidence of cervical cancer, the qualities of the VIA test may improve. Therefore, the “see- and-treat” method with VIA could be accepted by patients in developing countries like India. Conclusion: VIA is an adequate and acceptable screening method for cervical cancer. Furthermore, in low-resource areas like India, VIA can be better than cytology for its ease of use and low cost. Cytology based screen- ing programmes are difficult to organize owing to limited infrastructure, trained personnel, and funds. Our results outline the potential benefits of using VIA based screening at all levels of health care sys- tems in developing countries. There is therefore, the time has come, to integrate VIA based screening pro- grams at the primary care level of health services, and to downstage cancer cervix in our country. Visual Inspection with Acetic Acid (VIA) in cervical cancer screening 457 Author(s) Country No. of Women Sensitivity Specificity Megevand et al (1996) South Africa 2426 65 98 Londhe et al (1997) India 372 72 54 Zimbabwe University JHPIEGO (1999) Zimbabwe 2203 77 64 Denny et al (2000) Africa 2944 67 83 Belinson et al (2001) China 1977 71 74 Tayyeb et al (2003) Pakistan 501 93.9 30.4 Wu et al (2003) China 1997 70.9 74.3 Bhatla et al (2004) India 100 87.5 63 El – Shalakany et al (2004) Egypt 2049 85.5 96.8 Ghaemmahani et al (2004) Iran 1200 74.3 94 Sankaranarayanan et al (2004) India 18675 60.3 86.8 Goel et al (2005) New Delhi 400 96.7 36.4 Vuyst et al (2005) Nairobi (Kenya) 853 73.3 80.0 Shastri et al (2005) Mumbai (India) 4039 59.7 88.4 Doh et al (2005) Cameroon 4813 70.4 77.6 Eftekhar et al (2006) Iran 200 95.7 44.0 Sodhani et al (2006) India 472 86.7 90.7 Chumwonathayi et al (2008) Thailand 648 60.0 93.9 Cagle et al (2009) China 1839 69.5 89.0 Ardhahan et al (2011) Turkey 350 82.4 50 Present study India 942 74.16 50.0 Table 4: Comparison of Sensitivity and Specificity of VIA with Other Studies Shaheen, Sharma R, Rashi 458 References: 1. Sankaranarayanan R, Budukh AM, Rajkumar R. Effective screening programmes for cervical cancer in low-and middle-income developing countries. Bull World Health Organ. 2001;79(10):954-962. 2. Ferlay J et al., GLOBOCAN 2002: cancer incidence, mortality and prevalence world wide, version 2.0, Lyon, France: International Agency for Research on Cancer, 2004, , accessed May 16, 2008. 3. Haydaroglu A. Epidemiology in Gynaecologic Cancers. Izmir, Turkey: Gynaecologic Oncology Symposium; 2004. 4. Nygard JF, Skare GB, Thoresen SO. The cervical can- cer screening programme in Norway. 1992-2000: changes in pap smear coverage and incidence of cervix cancer. J Med Screen. 2002;9(2):86-91. http://dx.doi.org/10.1136/jms.9.2.86 5. Yuan CC, Wang PH. New strategies and advances in the management of cervical carcinoma. Gan To Kagaku Ryoho. 2002;29(1):143-149. 6. Saraiya U. Relevance cytology services in India today. J Obstet Gynecol India 1986; 36:374-384. 7. Gates B, Gates M. Pap smears: an important but imper- fect screening method. Alliance Cervical Cancer Prevention. Program for Appropriate Technology in Health (PATH). Washington, DC: Alliance Coordinating Agency; 2003. 8. Sing V, Schgal A, Parashari A, et al. Early detection of cervical cancer through acetic acid application an aided visual inspection. Singapore Med J. 2001;42(8):351- 354. 9. Tayyeb R, Khawaja NP, Malik N. Comparison of visu- al inspection of cervix and pap smear for cervical can- cer screening. J Coll Physicians Surg Pak.2003;13(4):201-203. 10. JHPIEGO Cervical Cancer Project. Visual inspection with acetic acid for cervical cancer screening: test qual- ities in a primary care setting. Lancet. 1 9 9 9 ; 3 5 3 ( 9 1 5 6 ) : 8 6 9 - 8 7 3 . http://dx.doi.org/10.1016/S0140-6736(98)07033-0 11. Ahmed T, Ashrafunnessa, Rahman J. Development of a visual inspection programme for cervical cancer pre- vention in Bangladesh. Reprod Health Matters. 2 0 0 8 ; 1 6 ( 3 2 ) : 7 8 - 8 5 . http://dx.doi.org/10.1016/S0968-8080(08)32419-7 12. Sankaranarayanan R et al. Visual inspection as a screening test for cervical cancer control in developing countries. In: Franco E, Monsonego J, eds.New devel- opments in cervical cancer screening and prevention. Oxford, Blackwell Science, 1997: 411–421. 13. Belinson JL, Pretorius RG, Zhang WH, et al. Cervical cancer screening by simple visual inspection after acetic acid. Obstet Gynecol. 2001;98(3):441-444. http://dx.doi.org/10.1016/S0029-7844(01)01454-5 14. Doh AS, Nkele NN, Achu P, et al. Visual inspection with acetic acid and cytology as screening methods for cervical lesions in Cameroon. Int J Gynecol Obstet. 2005;89(2):167-173. 32. 15. Londhe M, George SS, Seshadri L. Detection of CIN by naked eye visualization after application of acetic acid. Indian J Cancer. 1997;34(2):88-91. 16. Denny L, Kuhn L, Pollack A, et al. Evaluation of alter- native methods of cervical cancer screening for resource-poor settings. Cancer. 2000;89(4):826-833. h t t p : / / d x . d o i . o r g / 1 0 . 1 0 0 2 / 1 0 9 7 - 0142(20000815)89:4<826::AID-CNCR15>3.0.CO;2-5 17. Chumwonathayi B, Eamratsameekool W, Kularbkaew C, et al. Visual inspection with acetic acid test qualities in a secondary setting. J Obstet Gynaecol Res. 2 0 0 8 ; 3 4 ( 5 ) : 9 0 9 - 9 1 3 . http://dx.doi.org/10.1111/j.1447-0756.2008.00848.x 18. Goel A, Gandhi G, Batra S, et al. Visual inspection of the cervix with acetic acid for cervical intraepithelial lesions. Int J Gynaecol Obstet. 2005;88(1):25-30 http://dx.doi.org/10.1016/j.ijgo.2004.09.018 19. Megevand E, Denny L, Dehaeck K, et al. Acetic acid visualization of the cervix: an alternative to cytologic screening. Obstet Gynecol. 1996;88(3):383-386. http://dx.doi.org/10.1016/0029-7844(96)00189-5 20. Eftekhar Z, Rahimi M, Yarandi F, et al. Accuracy of visual inspection with acetic acid for early detection of cervical dysplasia in Tehran, IRAN. Asian Pac J Cancer Prev. 2005;6(1):69-71. 21. Bhatla N, Mukhopadhyay A, Joshi S, et al. Visual inspection for cervical cancer screening: evaluation by doctor versus paramedical worker. Indian J Cancer. 2004;41(1):32-36. 22. El-Shalakany A, Hassan SS, Ammar E, et al. Direct visual inspection of the cervix for the detection of pre- malignant lesions. J Low Genit Tract Dis. 2 0 0 4 ; 8 ( 1 ) : 1 6 - 2 0 . http://dx.doi.org/10.1097/00128360-200401000-00005 23. Basu PS, Sankaranarayanan R, Mandal R, et al. Visual inspection with acetic acid and cytology in the early detection of cervical neoplasia in Kolkata, India. Int J Gynecol Cancer. 2003;13(5):626-632. http://dx.doi.org/10.1046/j.1525-1438.2003.13394.x 24. Cagle AJ, Hu SY, Sellors JW, et al. Use of an expand- ed gold standard to estimate the accuracy of col- poscopy and visual inspection with acetic acid (VIA). Int J Cancer. 2010;126(1):156-161. http://dx.doi.org/10.1002/ijc.24719 25. Vuyst DH, Claeys P, Njiru S, et al. Comparison of pap smear, visual inspection with acetic acid, human Papillomavirus DNA-PCR testing and cervicography. Int J Gynaecol Obstet. 2005;89(2):120-126. http://dx.doi.org/10.1016/j.ijgo.2005.01.035 26. Ghaemmaghami F, Behtash N, Modares GM, et al. Visual inspection with acetic acid as a feasible screen- ing test for cervical neoplasia in Iran. Int J Gynecol Cancer. 2004;14(3):465-469. http://dx.doi.org/10.1111/j.1048-891x.2004.14306.x 27. Sankaranarayanan R, Shastri SS, Basu P, et al. The role of low-level magnification in visual inspection with acetic acid for the early detection of cervical neo- plasia. Cancer Detect Prev. 2004;28(5):345-351. http://dx.doi.org/10.1016/j.cdp.2004.04.004 28. Wu LY, Li N, Zhang WH, et al. Value of acetic acid smear test for cervical cancer screening, Ai Zheng. 2003;22(10):1096-1098. 29. Shastri S.S, Dinshaw K, Amin G, et al. Concurrent evaluation of visual, cytological & HPV testing as screening methods for the early detection of cervical neoplasia in Mumbai (India). Bull World Health Organization. 2005, 83;(3) doi: 10.1590/S0042- 96862005000300011. 30. Sodhani P, Gupta S, Sharma JK, et al. Test character- istics of various screening modalities for cervical can- cer: a feasibility study to develop an alternative strate- gy for resource-limited settings. Cytopathology. 2 0 0 6 ; 1 7 ( 6 ) : 3 4 8 - 3 5 2 . http://dx.doi.org/10.1111/j.1365-2303.2006.00351.x 31. Ardahan, Malek, Temel, Ayla. Visual inspection of acetic acid in cervical cancer screening. Canc. Nursing. 2 0 1 1 , 3 4 ; ( 2 ) : 1 5 8 - 1 5 3 . http://dx.doi.org/10.1097/NCC.0b013e3181efe69f Visual Inspection with Acetic Acid (VIA) in cervical cancer screening 459